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Highly Sensitive Protein Detection by Asymmetric Mach–Zehnder Interferometry for Biosensing ApplicationsClick to copy article linkArticle link copied!
- Melissa J. GoodwinMelissa J. GoodwinMESA+ Institute for Nanotechnology, Faculty of Science and Technology, University of Twente, 7522 NH Enschede, The NetherlandsMore by Melissa J. Goodwin
- Geert A. J. BesselinkGeert A. J. BesselinkLionix International, 7500 AL Enschede, The NetherlandsMore by Geert A. J. Besselink
- Floris Falke
- Arnoud S. EverhardtArnoud S. EverhardtLionix International, 7500 AL Enschede, The NetherlandsMore by Arnoud S. Everhardt
- Jeroen J. L. M. CornelissenJeroen J. L. M. CornelissenMESA+ Institute for Nanotechnology, Faculty of Science and Technology, University of Twente, 7522 NH Enschede, The NetherlandsMore by Jeroen J. L. M. Cornelissen
- Jurriaan Huskens*Jurriaan Huskens*Email: [email protected]MESA+ Institute for Nanotechnology, Faculty of Science and Technology, University of Twente, 7522 NH Enschede, The NetherlandsMore by Jurriaan Huskens
Abstract
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The sensitivity and performance of an asymmetric Mach–Zehnder interferometer (aMZI) were compared to those of quartz crystal microbalance with dissipation (QCM-D). The binding of streptavidin to sensor chips coated with poly-l-lysine (PLL), modified with biotin and oligoethyleneglycol (OEG) (PLL-biotin), was used to compare the binding signals obtained from both technologies. PLL-biotin proved to be an efficient method to add bioreceptors to both the QCM-D and aMZI chips. The final, saturated value of streptavidin binding was compared with those from aMZI (253 ng cm–2) and QCM-D (460 ng cm–2). These values were then used to evaluate that 45% of the measured streptavidin mass in the QCM-D came from hydrodynamically coupled water. Importantly, the signal-to-noise ratio of the aMZI was found to be 200 times higher than that of the QCM-D. These results indicate the potential of the aMZI platform for highly sensitive and accurate biosensing applications.
Copyright © 2020 American Chemical Society
Introduction
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Biosensors (1−3) have seen a great increase of interest in the last years, where they encompass devices as common as blood glucose sensors for helping the maintenance of blood sugar for diabetics, (4) to as specialistic as the detection of biomarkers for specific cancers. (5,6) Such biosensors are hereby used to detect (bio)chemical compounds mediated by isolated enzymes, immunosystems, tissues, organelles, or whole cells utilizing, for example, electrochemical (7−11) and optical devices. (12−14)
Optical biosensors have several key advantages over other methods. As they are significantly less affected by electromagnetic interference, they can be self-referencing, contain an antifouling reference on the same chip as the detector, and they can also be integrated with common optical methods like Raman scattering, which makes use of the unique fingerprint of an analyte to perform in situ spectroscopy. (15) A biosensor needs both specificities for the desired analyte, even in a complex matrix such as blood, and high sensitivity to the analyte to detect the markers in concentrations that can be as low as femtogram per milliliter. (16) Up to now, electrochemical sensors have been able to reach sensitivities that optics could not rival. (17) However, recent advances in the field of optics and integrated optics have greatly reduced the limit of detection of optical biosensors down to biologically relevant values. (18,19)
One such optical technique is the asymmetric Mach–Zehnder interferometer (aMZI), which detects changes in the refractive index. (20,21) The aMZI devices used in this study were fabricated using TriPleX technology. (22) The fabricated chips consist of stoichiometric Si3N4 waveguides with SiO2 cladding, which forms a photonic integrated circuit (PIC). The SiO2 cladding is locally removed to form the so-called sensing window, which allows the analyte to make contact with the waveguide. In the aMZI design, the waveguide splits the incoming light into two arms, one of which is exposed to the analyte and the other is never exposed to the analyte and used as a reference. This asymmetry is introduced deliberately in the interferometer to allow an interference pattern to be detected on the recombination of the two aMZI arms. When the analyte solution interacts with the evanescent field of the waveguide in the sensing window, changes in the refractive index result in a phase shift of the laser wavelength (in picometer, pm) in the interference pattern. The aMZI is sensitive both to changes in the refractive index of the liquid (the bulk shift) and the binding of the targeted specific analyte to the surface. (18,23) Initial proof-of-concept experiments have been performed using these aMZI devices as biosensors, (20,24−29) but it is important to perform a direct comparison of this technique to the current standard technology to verify its efficacy.
To provide a proof of concept of using the aMZI as a biosensor, it is necessary to have a method of reliably attaching bioreceptors to the substrate to achieve selectivity and specificity. One such method is the use of poly-l-lysine (PLL). PLL provides a versatile and robust method of attaching (bio)probes to a wide range of different substrates. (30,31) The charged amine groups of the lysine moieties enable PLL to strongly adsorb to any negatively charged surface, such as any surface that can be treated with UV/ozone, oxygen plasma, NaOH, or piranha solution. The lysine amines can be readily modified in controllable densities using bifunctional N-hydroxysuccinimide (NHS) esters, allowing the attachment of a nearly limitless variety of probes.
In this work, the aMZI platform is compared to a commercially available quartz crystal microbalance with dissipation (QCM-D) in terms of the absolute response and signal-to-noise ratio. To reach this aim, biotin-modified PLL was used to reliably attach probes to both the aMZI and QCM-D chips, and the stepwise binding of increasing streptavidin concentrations to the PLL-biotin was monitored by both techniques. The final saturated binding of streptavidin and the signal-to-noise ratio were compared between the aMZI and the QCM-D.
Results
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The chips used for the aMZI experiments contain six parallel aMZI devices on a single chip, as can be seen in Figure 1, allowing for six simultaneous measurements. There is a single microfluidic channel for analyte injection over the whole chip with the liquid flowing from the top to the bottom of the chip. As there are six sensing windows, six measurements can be potentially performed at the same time, pending the selective binding of probes to each sensing window in a controlled fashion.
Figure 1
Figure 1. Photograph of an aMZI chip with lithographically defined Si3N4 waveguides showing the six parallel aMZI devices (arranged top to bottom). Each aMZI device consists of a reference channel (left), which is closed (covered by SiO2), and an analyte channel (right), which is open to the flow of liquids.
PLL adsorbs readily to cleaned Si3N4, as well as the surrounding SiO2, through electrostatic interactions and is not removed by rinsing with, or even sonicating in, buffer. Once a sample of PLL has been successfully adsorbed on the surface, the surface is saturated with PLL and no further PLL can be adsorbed, meaning that there is no run over between analytes upon washing. Adding 10% glycerol to the PLL solution helps to prevent drying of the small quantities required to cover a sensing window, which greatly eases the process when spotting by hand with a pipette. To prevent any possible crossover due to the 200 μm gaps in between the sensing windows, the top two sensors were spotted with PLL-biotin, i.e., PLL modified with the probe moiety, and the bottom two with PLL-OEG, i.e., PLL modified only with OEG chains that provide antifouling properties. A schematic of the adsorption of PLL-biotin and the subsequent binding of streptavidin and the structures of the modified PLLs can be found in Figure 2. The middle two sensors were left free to avoid any accidental mixing of the droplets and thus contamination between the two PLL analytes. The data from different spotting experiments were not always identical, and the most reliable functionalization was only obtained after submerging the full chip in the PLL solution, showing that the spotting procedure does not lead to the perfect coverage for this combination of PLL and aMZI chips. The poorer reproducibility and crossover occurring during spotting currently limit the number of different analytes that can be accurately and reproducibly measured to one, by submerging the whole chip. A reference could be added by blocking the receptors of some windows after functionalization with PLL by spotting streptavidin onto the desired reference windows to block the receptors. To increase the number of different analytes that can be measured simultaneously, further research into spotting (such as using an automated spotting device, changing the solution composition, varying the surface preparation, and cleaning methods or applying heat or mechanical agitation to help increase the PLL coverage) and/or the design of a microfluidic device (that would allow addressing the windows individually) would be required.
Figure 2
Figure 2. (a) Schematic of the adsorption of PLL-biotin and PLL-OEG, and the subsequent binding of streptavidin to the biotin moieties. (b) Structures of PLL-OEG (left) and PLL-biotin (right).
In contrast to the aMZI, the QCM-D consists of four separate chambers, each of which houses a chip. This makes the introduction of up to four different coatings trivial, as each chip can be processed completely separately. We chose Si3N4-coated QCM-D chips to best match the waveguides of the aMZI chips. On the aMZI chips, the PLL solutions were introduced by adding a drop of PLL solution in phosphate-buffered saline (PBS) with 10% glycerol to cover the whole of the sensor surface; for a direct comparison, the QCM-D chips were coated by the same method, using either PLL-OEG, as a background experiment to verify the antifouling properties of PLL-OEG, or PLL-biotin to bind the analyte streptavidin.
After the adsorption of PLL, solutions of streptavidin were put in contact with the coated substrates. The conditions of the QCM-D and aMZI experiments were chosen to be as closely relatable as possible. A flow rate of 15 μL min–1 was used for both techniques. For the aMZI, a syringe pump filled with PBS buffer was used to flow buffer over the chip. While the chamber was flushed with buffer, the 200 μL sample loop was filled with the streptavidin solution (0–1 μM in PBS, pH 7.2) using a separate peristaltic pump. After the loop was filled, the flow of the syringe pump over the chip was changed to include the 200 μL sample loop to allow for a smooth flow of the streptavidin solution over the chip without ever stopping the flow through the chamber housing the chip. After each addition of streptavidin, this procedure could be repeated with different concentrations of streptavidin. Each buffer wash step was performed for 10 min. For the QCM-D experiments, the buffer steps were performed for 10 min and the streptavidin steps for 13.3 min to achieve approximately the same volume of 200 μL, which was used in the aMZI experiments. To change the sample, the flow was stopped, the sample vials were changed, and then the flow was resumed.
In QCM experiments, a change in mass density Δm (ng cm–2) on the chip is obtained by following the change in frequency Δf (Hz), and they are related to each other by the Sauerbrey equation (32)
where C is the Sauerbrey constant (17.7 Hz ng–1 cm–2).
(1)
In these QCM-D experiments, the PLL-OEG sample shows no binding at any concentration of streptavidin as can be seen in Figure 3a. Small “waves” can be seen with the change between buffer and streptavidin and back; these arise from a change in viscosity in the solution and not from any interaction between the streptavidin and the surface. These results verify the ability of PLL-OEG as an antifouling layer for streptavidin.
Figure 3
Figure 3. QCM-D (frequency, left axis, and dissipation, right axis) data of increasing concentrations of streptavidin (values given in the graph; buffer flow when no concentration is given) at substrates coated with (a) PLL-OEG and (b) PLL-biotin.
The PLL-biotin-coated chip exhibits stepwise decreases in frequency upon exposure to increasing concentrations of streptavidin, which do not recover upon flushing with buffer (Figure 3b). The small peaks apparent in Figure 3b arise from the stopping and starting of the flow to change the solutions. There is a delay between the changing of the solution and the sample reaching the chamber due to the length of the tubing before the chamber. The observed frequency changes result from the binding of streptavidin to the surface, and the absence of recovery is caused by the strong, practically irreversible biotin–streptavidin interaction. Increasing the concentration of streptavidin does increase the change in frequency, as can be seen from the change between 50 and 100 nM. From concentrations of 200 nM and higher, the surfaces become saturated, and any further increase in concentration no longer changes this frequency by a significant amount. The final total change in frequency is −26 Hz, which is comparable to previous results for a complete and saturated layer of streptavidin. (33,34)
The Sauerbrey equation is only applicable when the layer formed can be assumed to be rigid. As a rule, if the change in dissipation, which is a measure of the rigidity of the layer, is less than 2.0 × 10–6, the layer can be treated as rigid. (35) The maximum dissipation change observed in the experiments was 0.35 × 10–6, so it can be deemed appropriate to use the Sauerbrey equation. Using the Sauerbrey equation, a Δf of −26 Hz corresponds to a Δm of 460 ng cm–2. This mass change includes all water coupled hydrodynamically to the hydrophilic streptavidin, as QCM-D measures all mass and does not differentiate between coupled water and analyte. This means that it is required to compare QCM-D results to those of other techniques if the absolute streptavidin mass density is desired.
Figure 4 shows the data collected during the streptavidin binding experiments at the aMZI platform. When switching between PBS and the streptavidin solutions, there is a significant change in the refractive index, as shown in Figure 4a, recorded in the measurement as a phase shift (in pm). As the aMZI records all sensors at the same time and the PLL-OEG is an effective antifouling layer, as shown in the QCM-D experiment, it is possible to subtract this reference data in Figure 4b to subtract the effects of the bulk refractive index changes to record only the amount of binding on the surface without bulk effects.
Figure 4
Figure 4. aMZI data showing the binding of streptavidin (values given in the graph; buffer flow when no concentration is given) to PLL-biotin: (a) raw data and (b) data with reference subtracted.
The streptavidin binding does not saturate until the final value is reached at a concentration of 1000 nM of streptavidin. The difference between saturation concentration between QCM-D and aMZI is due to the actual flow in the chambers affecting the kinetics of binding. An in-depth analysis of adsorption kinetics and mass transport is beyond the scope of this work. Further work using higher flow rates would highlight the differences between the two techniques. Using a higher flow rate would greatly reduce the contribution of diffusion kinetics in the aMZI, allowing the fast streptavidin–biotin binding to be observed. The effects of the increased flow rate would be less significant in the QCM-D due to the large size of the sample chamber. By varying the flow rate in the aMZI, it would be possible to optimize experiments to either observe binding kinetics of strong binding events at high flow or detect low concentrations of precious analytes at a low flow rate. This flexibility would not be as easily achieved using the QCM-D. These parameters will benefit from the optimized design of the microfluidics chamber around the sensor windows, as mentioned above.
The final average shift value from the streptavidin binding experiment on the aMZI is 8722 pm ± 4%, where the variation is comparable to the typical 3% sensitivity variations found for this design right after fabrication. The slight increase is likely due to small variations in the PLL monolayer coverage and subsequent binding.
To analyze the data from the aMZI streptavidin binding and extract an adsorbed mass density, the relationship between the shift of the interference signal in pm and the protein binding should be established. Following work with comparable binding experiments on microring resonators (MRRs) with the same TriPleX technology, it was found that those MRR sensors have the same sensitivity to changes in refractive index for adsorption on the surface and for bulk changes. (22,36) Assuming the same sensitivity relationship for these aMZI devices, eq 2 (derived in the Experimental Section) can be used to calculate the mass density of streptavidin binding as
where ΔΓ is the change in mass per area in ng cm–2, K is a custom-designed value of 0.029 ng pm–1 cm–2, and Δλ is the observed change in shift in pm. The average shift change of the streptavidin-saturated PLL-biotin was found to be 8722 pm, which uses eq 2 to give a mass density of 253 ng cm–2.
(2)
Discussion
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The QCM-D and the aMZI measurements yielded mass densities of 460 and 253 ng cm–2, respectively. While the QCM-D system includes hydrodynamically coupled water in the measurement, the aMZI platform does not because the adsorbed water has practically the same refractive index as the buffer and thus does not result in a measurable refractive index change. Assuming that the difference in final mass density between the two techniques can be wholly attributed to co-adsorbed water, the percentage of the water hydrodynamically coupled to the streptavidin is found to be 45% of the recorded mass in the QCM-D. Larsson et al. (33) found in their comparison between surface plasmon resonance (SPR) and QCM-D that 55% of the measured mass in the binding of streptavidin on the QCM-D was from water. This is comparable to the value achieved from our comparison of the QCM-D data with the aMZI. Both SPR and aMZI are evanescent field-based optical sensing technologies that probe the near-surface area (penetration depth ≈100–200 nm) of the liquid on top of the sensor surface for changes in the refractive index of the probe volume. Binding of protein molecules onto the sensor surface leads to such an increase in the refractive index. Both methods allow monitoring the binding of protein and to quantitatively express its adsorbed (dry) surface mass density (ng cm–2). Differences could arise from the assumptions required to formulate a general equation for the technique, such as simulated sensitivities or assumptions over protein density, for both the aMZI and SPR. Another cause could be that the system measured is not exactly the same. Larsson et al. bound streptavidin to a thiol monolayer formed on gold, opposed to the PLL on Si3N4 used in the aMZI experiments. The addition of OEG for antifouling or the inherent hydrophilicity of the PLL backbone could make a significant difference in the environment to which the streptavidin binds when compared to thiols on gold, as well as the use of a different buffer, which may also affect the interactions between water and the protein.
A second metric to compare the systems is the signal-to-noise ratio. If the noise is large compared to the signal, the sensitivity and reproducibility of the technique are reduced. In Figure 3, the variance in the QCM-D frequency signal is ∼0.6 Hz. Compared with the final binding of 26 Hz, this gives a signal-to-noise ratio of 43:1. In contrast, the aMZI data in Figure 4 has a noise level of ∼1 pm and an average maximum binding of 8722 pm, giving a signal-to-noise ratio of 8722:1. Thus. the aMZI has a 200-fold improvement in the signal-to-noise ratio when compared to the QCM-D. To establish a rough estimate of the detection limit, we can extrapolate the signal given by different concentrations from the signals for both methods at the 50 nM concentration to the point where the signal would be identical to the noise level of the technique. For QCM-D, the noise limit lies at 6 nM (a signal of 5 Hz with 0.6 Hz of noise), while for the aMZI this lies at 0.07 nM (a signal of 700 pm with 1 pm of noise). This would give a 100-fold increase in the detection limit for the aMZI method for this system at these conditions. However, because of the differences in the design of the fluidics of the two systems, a true comparison of the LOD is beyond the scope of this study. Overall, this comparison shows the great potential of the aMZI as a technique to employ at low concentrations or weakly binding analytes.
Conclusions
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The use of poly-l-lysine enables quick and simple attachment of bioreceptors onto both the aMZI and the QCM-D chips to allow a direct comparison between the two platforms. It was found that the aMZI measured streptavidin binding, which was comparable to literature and resulted in 45% hydrodynamically coupled water for the adsorption in the QCM-D. While the experimental conditions were chosen to best compare the two techniques, there were inevitably some differences between the systems with respect to the actual flow rates over the chip due to different chamber sizes, tubing widths, and sensor areas. For a complete study of comparable limits of detection, the binding kinetics, and mass transport, modeling of the flow within both the QCM-D and the aMZI flow chambers would be required.
Although PLL allowed the attachment of bioreceptors on both the QCM-D and aMZI chips, there was a small discrepancy in the PLL spotting consistency on the aMZI chip when doing microspotting. Even though the difference in signal is not too large to adversely affect the binding of streptavidin to biotin at the concentrations presented here, for future work, if a less strongly binding or low-concentration analyte is used, assuring a dense and complete layer of receptors would be crucial.
In conclusion, the aMZI platform proved to be a highly effective tool for biosensing compared to the established technology of QCM-D. First, it enabled the measurement of streptavidin binding without the added complication of hydrodynamically coupled water, allowing the elucidation of the absolute protein mass adsorption. Second, the aMZI exhibited a 200-fold increase in the signal-to-noise ratio and thus has the potential to have a significantly lower limit of detection. The ease of attaching up to six separate bioreceptors to the chip and measuring them all simultaneously allows the aMZI to be a flexible technique capable of self-referencing. The aMZI has the potential for label-free, low-concentration detection, and quantification of a wide variety of biological analytes.
Experimental Section
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Poly-l-lysine hydrobromide (MW 15–30 kDa) was purchased from Sigma-Aldrich and dissolved in PBS (10 mM, pH 7.2) to make a stock solution of 1 mg mL–1. EZ-Link (NHS-biotin) and MS(PEG)4 (methyl-PEG-NHS-ester) were purchased from Thermo Fisher Scientific and dissolved in dimethyl sulfoxide (DMSO) to make a stock solution of 1 mg mL–1. Streptavidin was purchased from Sigma-Aldrich and dissolved in MilliQ water to make a 1 mg mL–1 stock solution. All compounds were used without further purification.
PLL-biotin(10%)-OEG(30%) (PLL-biotin) and PLL-OEG(35%) (PLL-OEG) were synthesized and characterized by the methods of Duan et al. (37) The modified PLLs were dissolved in PBS (10 mM, pH 7.2) with 10% glycerol at a concentration of 1.5 mg mL–1. PLL-biotin and PLL-OEG were immobilized on clean aMZI and QCM chips by dropping the solution of the desired PLL to cover the sensing windows of the aMZI and whole QCM chip. The chips were left for 5 min before being thoroughly rinsed with MilliQ water then dried under a stream of nitrogen.
QCM-D experiments were performed on a Q-Sense E4 4-channel quartz crystal microbalance with a peristaltic pump (Biolin Scientific) using a flow rate of 15 μL min–1 and Si3N4-coated quartz chips (Biolin Scientific). The equipment was equilibrated in PBS for 30 min and reagents were flushed for 13.3 min. Si3N4 QCM-D chips were cleaned in UV–ozone using Bioforce UV/Ozone ProCleaner Plus for 30 min.
The aMZI experiments were performed at Lionix International using a home-built setup (Figure 5). The aMZI chips were cleaned using a cotton swab and a solution of 0.25 M NaOH with 1% Triton X-100, followed by thorough rinsing with deionized water and drying under a stream of nitrogen. The chips were placed in a flow cell with a piezoelectric alignment stage for the laser inputs. Experiments were performed using a 15 μL min–1 flow rate, a syringe pump to flush PBS (10 mM, pH 7.2), and a 200 μL sample loop with a peristaltic pump to fill the sample loop while the syringe pump never stopped the flow to the chip.
Figure 5
Figure 5. Photograph of the aMZI setup with the fluidic system and the piezoelectric auto-alignment stage.
To compensate for the change in bulk refractive index (Figure 4a), the PLL-OEG data was subtracted from all sensors to give Figure 4b. To compensate for the delay due to the direction of flow over the chip (Figure 1), the data of the later sensors was shifted in time by approximately an extra 0.5 s for each subsequent sensor before subtraction.
For the analysis of the aMZI data, eq 2 was derived from a comparison to previous work on the MRR. The observed change in shift is proportional to the adsorbed mass in both MMR and aMZI. The ratio between the bulk sensitivity for aMZI and MRR is equal to the ratio in surface sensitivity giving
Rearrangement of (eq 3) gives
The bulk sensitivity of the MMR was calculated by Heideman et al. (22) to be
The surface sensitivity, if it is assumed that proteins have an average mass density of 1.35 g cm3, was calculated by Besselink et al. (36) to be
Substitution of these values into (eq 4) and given that the sensitivity of the MZI chips is designed to be 2000 nm RIU–1 gives
Rearranging and simplifying (eq 5) gives eq 2.
(3)
(4)
(5)
Author Information
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- Jurriaan Huskens - MESA+ Institute for Nanotechnology, Faculty of Science and Technology, University of Twente, 7522 NH Enschede, The Netherlands;
http://orcid.org/0000-0002-4596-9179;
- Jeroen J. L. M. Cornelissen - MESA+ Institute for Nanotechnology, Faculty of Science and Technology, University of Twente, 7522 NH Enschede, The Netherlands;http://orcid.org/0000-0002-9728-5043
M.J.G. and G.A.J.B. performed the experiments and analyzed the results. All authors contributed to the writing of the manuscript.
This work was funded by OP Oost and the European Union as part of the Biomeander project.
Acknowledgments
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Dr. Almudena Marti Morant is thanked for providing the PLL-biotin.
| aMZI | asymmetric Mach–Zehnder interferometer |
| OEG | oligo(ethylene glycol) |
| PBS | phosphate-buffered saline |
| PLL | poly-l-lysine |
| MRR | microring resonator |
| QCM-D | quartz crystal microbalance with dissipation |
| SPR | surface plasmon resonance |
References
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- 3Neethirajan, S.; Ragavan, V.; Weng, X.; Chand, R. Biosensors for Sustainable Food Engineering: Challenges and Perspectives. Biosensors 2018, 8, 23 DOI: 10.3390/bios8010023Google Scholar3https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhsVKmt7%252FM&md5=d19b62f44ad958fe23083f8bfe7b5925Biosensors for sustainable food engineering: challenges and perspectivesNeethirajan, Suresh; Ragavan, Vasanth; Weng, Xuan; Chand, RohitBiosensors (2018), 8 (1), 23/1-23/34CODEN: BIOSHU; ISSN:2079-6374. (MDPI AG)Current food prodn. faces tremendous challenges from growing human population, maintaining clean resources and food qualities, and protecting climate and environment. Food sustainability is mostly a cooperative effort resulting in technol. development supported by both governments and enterprises. Multiple attempts have been promoted in tackling challenges and enhancing drivers in food prodn. Biosensors and biosensing technologies with their applications, are being widely applied to tackling top challenges in food prodn. and its sustainability. Consequently, a growing demand in biosensing technologies exists in food sustainability. Microfluidics represents a technol. system integrating multiple technologies. Nanomaterials, with its technol. in biosensing, is thought to be the most promising tool in dealing with health, energy, and environmental issues closely related to world populations. The demand of point of care (POC) technologies in this area focus on rapid, simple, accurate, portable, and low-cost anal. instruments. This review provides current viewpoints from the literature on biosensing in food prodn., food processing, safety and security, food packaging and supply chain, food waste processing, food quality assurance, and food engineering. The current understanding of progress, soln., and future challenges, as well as the commercialization of biosensors are summarized.
- 4Yoo, E. H.; Lee, S. Y. Glucose Biosensors: An Overview of Use in Clinical Practice. Sensors 2010, 10, 4558– 4576, DOI: 10.3390/s100504558Google Scholar4https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC383ps1Wgsg%253D%253D&md5=cfcc8dd4d944e63a772f3c181314e37bGlucose biosensors: an overview of use in clinical practiceYoo Eun-Hyung; Lee Soo-YounSensors (Basel, Switzerland) (2010), 10 (5), 4558-76 ISSN:.Blood glucose monitoring has been established as a valuable tool in the management of diabetes. Since maintaining normal blood glucose levels is recommended, a series of suitable glucose biosensors have been developed. During the last 50 years, glucose biosensor technology including point-of-care devices, continuous glucose monitoring systems and noninvasive glucose monitoring systems has been significantly improved. However, there continues to be several challenges related to the achievement of accurate and reliable glucose monitoring. Further technical improvements in glucose biosensors, standardization of the analytical goals for their performance, and continuously assessing and training lay users are required. This article reviews the brief history, basic principles, analytical performance, and the present status of glucose biosensors in the clinical practice.
- 5Khanmohammadi, A.; Aghaie, A.; Vahedi, E.; Qazvini, A.; Ghanei, M.; Afkhami, A.; Hajian, A.; Bagheri, H. Electrochemical Biosensors for the Detection of Lung Cancer Biomarkers: A Review. Talanta 2020, 206, 120251 DOI: 10.1016/j.talanta.2019.120251Google Scholar5https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhsF2msb7L&md5=84f559a8344e3839fd6e976b67dd439cElectrochemical biosensors for the detection of lung cancer biomarkers: A reviewKhanmohammadi, Akbar; Aghaie, Ali; Vahedi, Ensieh; Qazvini, Ali; Ghanei, Mostafa; Afkhami, Abbas; Hajian, Ali; Bagheri, HasanTalanta (2020), 206 (), 120251CODEN: TLNTA2; ISSN:0039-9140. (Elsevier B.V.)A review. Cancer is one of the most widespread challenges and important diseases, which has the highest mortality rate. Lung cancer is the most common type of cancer, so that ∼25% of all cancer deaths are related to the lung cancer. The lung cancer is classified as two different types with different treatment methodol.: the small cell lung carcinoma and nonsmall cell lung carcinoma are two categories of the lung cancer. Since the lung cancer is often in the latent period in its early stages, therefore, early diagnosis of lung cancer has many challenges. Hence, there is a need for sensitive and reliable tools for preclin. diagnosis of lung cancer. Therefore, many detection methods have been employed for early detection of lung cancer. As lung cancer tumors growth in the body, the cancerous cells release numerous DNA, proteins, and metabolites as special biomarkers of the lung cancer. The levels of these biomarkers show the stages of the lung cancer. Therefore, detection of the biomarkers can be used for screening and clin. diagnosis of the lung cancer. There are numerous biomarkers for the lung cancer such as EGFR, CEA, CYFRA 21-1, ENO1, NSE, CA 19-9, CA 125 and VEGF. Nowadays, electrochem. methods are very attractive and useful in the lung cancer detections. So, the recent advances and improvements (2010-2018) in the electrochem. detection of the lung cancer biomarkers have been reviewed.
- 6Qian, L.; Li, Q.; Baryeh, K.; Qiu, W.; Li, K.; Zhang, J.; Yu, Q.; Xu, D.; Liu, W.; Brand, R. E. Biosensors for Early Diagnosis of Pancreatic Cancer: A Review. Transl. Res. 2019, 213, 67– 89, DOI: 10.1016/j.trsl.2019.08.002Google Scholar6https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhs1WisL7N&md5=9f74ee2b04e7feb57c0e40bf58c700b5Biosensors for early diagnosis of pancreatic cancer: a reviewQian, Lisheng; Li, Qiaobin; Baryeh, Kwaku; Qiu, Wanwei; Li, Kun; Zhang, Jing; Yu, Qingcai; Xu, Dongqin; Liu, Wenju; Brand, Randall E.; Zhang, Xueji; Chen, Wei; Liu, GuodongTranslational Research (2019), 213 (), 67-89CODEN: TRRECL; ISSN:1878-1810. (Elsevier B.V.)A review. Pancreatic cancer is characterized by extremely high mortality and poor prognosis and is projected to be the leading cause of cancer deaths by 2030. Due to the lack of early symptoms and appropriate methods to detect pancreatic carcinoma at an early stage as well as its aggressive progression, the disease is often quite advanced by the time a definite diagnosis is established. The 5-yr relative survival rate for all stages is approx. 8%. Therefore, detection of pancreatic cancer at an early surgically resectable stage is the key to decrease mortality and to improve survival. The traditional methods for diagnosing pancreatic cancer involve an imaging test, such as ultrasound or magnetic resonance imaging, paired with a biopsy of the mass in question. These methods are often expensive, time consuming, and require trained professionals to use the instruments and analyze the imaging. To overcome these issues, biosensors have been proposed as a promising tool for the early diagnosis of pancreatic cancer. The present critically discusses the latest developments in biosensors for the early diagnosis of pancreatic cancer. Protein and microRNA biomarkers of pancreatic cancer and corresponding biosensors for pancreatic cancer diagnosis have been ed, and all these cases demonstrate that the emerging biosensors are becoming an increasingly relevant alternative to traditional techniques. In addn., we discuss the existing problems in biosensors and future challenges.
- 7Sanati, A.; Jalali, M.; Raeissi, K.; Karimzadeh, F.; Kharaziha, M.; Mahshid, S. S.; Mahshid, S. A Review on Recent Advancements in Electrochemical Biosensing Using Carbonaceous Nanomaterials. Microchim. Acta 2019, 186, 773 DOI: 10.1007/s00604-019-3854-2Google Scholar7https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXitFKrsb3I&md5=2c4aed6e2ccb9bba62f152a8329499c9A review on recent advancements in electrochemical biosensing using carbonaceous nanomaterialsSanati, Alireza; Jalali, Mahsa; Raeissi, Keyvan; Karimzadeh, Fathallah; Kharaziha, Mahshid; Mahshid, Sahar Sadat; Mahshid, SaraMicrochimica Acta (2019), 186 (12), 773CODEN: MIACAQ; ISSN:0026-3672. (Springer-Verlag GmbH)This review, with 201 refs., describes the recent advancement in the application of carbonaceous nanomaterials as highly conductive platforms in electrochem. biosensing. The electrochem. biosensing is described in introduction by classifying biosensors into catalytic-based and affinity-based biosensors and statistically demonstrates the most recent published works in each category. The introduction is followed by sections on electrochem. biosensors configurations and common carbonaceous nanomaterials applied in electrochem. biosensing, including graphene and its derivs., carbon nanotubes, mesoporous carbon, carbon nanofibers and carbon nanospheres. In the following sections, carbonaceous catalytic-based and affinity-based biosensors are discussed in detail. In the category of catalytic-based biosensors, a comparison between enzymic biosensors and non-enzymic electrochem. sensors is carried out. Regarding the affinity-based biosensors, scholarly articles related to biol. elements such as antibodies, DNAs (DNAs) and aptamers are discussed in sep. sections. The last section discusses recent advancements in carbonaceous screen-printed electrodes as a growing field in electrochem. biosensing. Tables are presented that give an overview on the diversity of analytes, type of materials and the sensors performance. Ultimately, general considerations, challenges and future perspectives in this field of science are discussed. Recent findings suggest that interests towards 2D nanostructured electrodes based on graphene and its derivs. are still growing in the field of electrochem. biosensing. That is because of their exceptional elec. cond., active surface area and more convenient prodn. methods compared to carbon nanotubes. [Figure not available: see fulltext.].
- 8Blair, E. O.; Corrigan, D. K. A Review of Microfabricated Electrochemical Biosensors for DNA Detection. Biosens. Bioelectron. 2019, 134, 57– 67, DOI: 10.1016/j.bios.2019.03.055Google Scholar8https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXmvFSnu74%253D&md5=38386a96b0e01854791460963cbb5464A review of microfabricated electrochemical biosensors for DNA detectionBlair, Ewen O.; Corrigan, Damion K.Biosensors & Bioelectronics (2019), 134 (), 57-67CODEN: BBIOE4; ISSN:0956-5663. (Elsevier B.V.)This review article presents an overview of recent work on electrochem. biosensors developed using microfabrication processes, particularly sensors used to achieve sensitive and specific detection of DNA sequences. Such devices are important as they lend themselves to miniaturization, reproducible mass-manuf., and integration with other previously existing technologies and prodn. methods. The review describes the current state of these biosensors, novel methods used to produce them or enhance their sensing properties, and pathways to deployment of a complete point-of-care biosensing system in a clin. setting.
- 9Batool, R.; Rhouati, A.; Nawaz, M. H.; Hayat, A.; Marty, J. L. A Review of the Construction of Nano-Hybrids for Electrochemical Biosensing of Glucose. Biosensors 2019, 9, 46 DOI: 10.3390/bios9010046Google Scholar9https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXisVGru7bE&md5=3b6d1879d8b2eb77b68f75a3e6029bb2A review of the construction of nano-hybrids for electrochemical biosensing of glucoseBatool, Razia; Rhouati, Amina; Nawaz, Mian Hasnain; Hayat, Akhtar; Marty, Jean LouisBiosensors (2019), 9 (1), 46CODEN: BIOSHU; ISSN:2079-6374. (MDPI AG)Continuous progress in the domain of nano and material science has led to modulation of the properties of nanomaterials in a controlled and desired fashion. In this sense, nanomaterials, including carbon-based materials, metals and metal oxides, and composite/hybrid materials have attracted extensive interest with regard to the construction of electrochem. biosensors. The modification of a working electrode with a combination of two or three nanomaterials in the form of nano-composite/nano-hybrids has revealed good results with very good reproducibility, stability, and improved sensitivity. This review paper is focused on discussing the possible constructs of nano-hybrids and their subsequent use in the construction of electrochem. glucose biosensors.
- 10Wang, W.; Su, H.; Wu, Y.; Zhou, T.; Li, T. Review-Biosensing and Biomedical Applications of Graphene: A Review of Current Progress and Future Prospect. J. Electrochem. Soc. 2019, 166, B505– B520, DOI: 10.1149/2.1231906jesGoogle Scholar10https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXpvFSltbk%253D&md5=7e099789cee74c6b66bc716ef3b1a831Review-biosensing and biomedical applications of graphene: a review of current progress and future prospectWang, Weiran; Su, Hengjie; Wu, Yuxiang; Zhou, Teng; Li, TingJournal of the Electrochemical Society (2019), 166 (6), B505-B520CODEN: JESOAN; ISSN:0013-4651. (Electrochemical Society)Graphene has generated widely interest in biosensor study because it had a large surface area, excellent elec. and thermal cond., high mech. strength and other unique phys. and chem. properties. In this paper, graphene was reviewed from three aspects. Firstly, several common fabrication methods and characteristics of graphene were introduced. Secondly, applications of the nanosized graphene (NG) and nanosized graphene oxide (NGO) in biosensor and medical imaging were discussed. The NG and NGO had the characteristics of photoluminescence. Based on the fluorescence quenching nature of the graphene surface, the targeting mols. could be confirmed by detecting the fluorescent substance. In addn., the graphene oxide (GO) had a promising prospect in the field of surface-enhanced Raman imaging. In the field of electrochem., graphene and its derivs. could be modified on the surface to couple with ligands and antigens and were able to detect specific biomols., such as glucose, DNA, proteins and etc. Thirdly, this paper introduced graphene applications in medical treatment. Due to the inherent high near-IR (NIR) absorbance, graphene materials were widely used in the treatment of in vivo cancer photothermal therapy. The combination of the graphene, anticancer drugs, and specific antigens was highly efficient for drug delivery. This paper summarized the achievements of graphene materials in the medical diagnostics, the presents challenges, and the future prospect.
- 11Syu, Y. C.; Hsu, W. E.; Lin, C. T. Review-Field-Effect Transistor Biosensing: Devices and Clinical Applications. ECS J. Solid State Sci. Technol. 2018, 7, Q3196– Q3207, DOI: 10.1149/2.0291807jssGoogle Scholar11https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhsVKju73J&md5=21c12f2b74737b49e7bc2d84288e092fReview-Field-Effect Transistor Biosensing: Devices and Clinical ApplicationsSyu, Yu-Cheng; Hsu, Wei-En; Lin, Chih-TingECS Journal of Solid State Science and Technology (2018), 7 (7), Q3196-Q3207CODEN: EJSSBG; ISSN:2162-8769. (Electrochemical Society)A review. Biosensor research has been addressed as an interested field recently. Within different kinds of developed biosensing technologies, field-effect transistor (FET) based biosensors stand out due to their attractive features, such as ultra-sensitivity detection, mass-prodn. capability, and low-cost manufg. To promote understandings of the FET based biosensing technol., in this review, its sensing mechanism is introduced, as well as major FET-based biosensing devices: ion sensitive field-effect transistor (ISFET), silicon nanowire, org. FET, graphene FET, and compd.-semiconductor FET. In addn. to FET-based biosensing devices, clin. applications, such as cardiovascular diseases (CVDs), cancers, diabetes, HIV, and DNA sequence, are also reviewed. In the end, several crit. challenges of FET-based biosensing technol. are discussed to envision next steps in healthcare technologies.
- 12Garzón, V.; Pinacho, D. G.; Bustos, R. H.; Garzón, G.; Bustamante, S. Optical Biosensors for Therapeutic Drug Monitoring. Biosensors 2019, 9, 132 DOI: 10.3390/bios9040132Google Scholar12https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtFOgtbzJ&md5=c6097c01de834ab022d21a603d7db7fcOptical biosensors for therapeutic drug monitoringGarzon, Vivian; Pinacho, Daniel G.; Bustos, Rosa-Helena; Garzon, Gustavo; Bustamante, SandraBiosensors (2019), 9 (4), 132CODEN: BIOSHU; ISSN:2079-6374. (MDPI AG)Therapeutic drug monitoring (TDM) is a fundamental tool when administering drugs that have a limited dosage or high toxicity, which could endanger the lives of patients. To carry out this monitoring, one can use different biol. fluids, including blood, plasma, serum, and urine, among others. The help of specialized methodologies for TDM will allow for the pharmacodynamic and pharmacokinetic anal. of drugs and help adjust the dose before or during their administration. Techniques that are more versatile and label free for the rapid quantification of drugs employ biosensors, devices that consist of one element for biol. recognition coupled to a signal transducer. Among biosensors are those of the optical biosensor type, which have been used for the quantification of different mols. of clin. interest, such as antibiotics, anticonvulsants, anti-cancer drugs, and heart failure. This review presents an overview of TDM at the global level considering various aspects and clin. applications. In addn., we review the contributions of optical biosensors to TDM.
- 13Mejía-Salazar, J. R.; Oliveira, O. N. Plasmonic Biosensing. Chem. Rev. 2018, 118, 10617– 10625, DOI: 10.1021/acs.chemrev.8b00359Google Scholar13https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhslKhtrbP&md5=33112eac9bdb55911c28aa95b098bb8ePlasmonic BiosensingMejia-Salazar, J. R.; Oliveira, Osvaldo N.Chemical Reviews (Washington, DC, United States) (2018), 118 (20), 10617-10625CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review. Plasmonic biosensing has been used for fast, real-time, and label-free probing of biol. relevant analytes, where the main challenges are to detect small mols. at ultralow concns. and produce compact devices for point-of-care (PoC) anal. This review discusses the most recent, or even emerging, trends in plasmonic biosensing, with novel platforms which exploit unique physicochem. properties and versatility of new materials. In addn. to the well-established use of localized surface plasmon resonance (LSPR), three major areas have been identified in these new trends: chiral plasmonics, magnetoplasmonics, and quantum plasmonics. In describing the recent advances, emphasis is placed on the design and manuf. of portable devices working with low loss in different frequency ranges, from the IR to the visible.
- 14Peltomaa, R.; Glahn-Martínez, B.; Benito-Peña, E.; Moreno-Bondi, M. C. Optical Biosensors for Label-Free Detection of Small Molecules. Sensors 2018, 18, 4126 DOI: 10.3390/s18124126Google Scholar14https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhtFagtLzN&md5=8567f91fe7042dc59217b37f021ab506Optical biosensors for label-free detection of small moleculesPeltomaa, Riikka; Glahn-Martinez, Bettina; Benito-Pena, Elena; Moreno-Bondi, Maria C.Sensors (2018), 18 (12), 4126/1-4126/46CODEN: SENSC9; ISSN:1424-8220. (MDPI AG)A review. Label-free optical biosensors are an intriguing option for the analyses of many analytes, as they offer several advantages such as high sensitivity, direct and real-time measurement in addn. to multiplexing capabilities. However, development of label-free optical biosensors for small mols. can be challenging as most of them are not naturally chromogenic or fluorescent, and in some cases, the sensor response is related to the size of the analyte. To overcome some of the limitations assocd. with the anal. of biol., pharmacol., or environmentally relevant compds. of low mol. wt., recent advances in the field have improved the detection of these analytes using outstanding methodol., instrumentation, recognition elements, or immobilization strategies. In this review, we aim to introduce some of the latest developments in the field of label-free optical biosensors with the focus on applications with novel innovations to overcome the challenges related to small mol. detection. Optical label-free methods with different transduction schemes, including evanescent wave and optical fiber sensors, surface plasmon resonance, surface-enhanced Raman spectroscopy, and interferometry, using various biorecognition elements, such as antibodies, aptamers, enzymes, and bioinspired molecularly imprinted polymers, are reviewed.
- 15Juan-Colás, J.; Johnson, S.; Krauss, T. F. Dual-Mode Electro-Optical Techniques for Biosensing Applications: A Review. Sensors 2017, 17, 2047 DOI: 10.3390/s17092047Google Scholar15https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXkt1Cnu7s%253D&md5=8011b1fc0f3ea29f48fd8b35969635ecDual-mode electro-optical techniques for biosensing applications: a reviewJuan-Colas, Jose; Johnson, Steven; Krauss, Thomas F.Sensors (2017), 17 (9), 2047/1-2047/15CODEN: SENSC9; ISSN:1424-8220. (MDPI AG)The monitoring of biomol. interactions is a key requirement for the study of complex biol. processes and the diagnosis of disease. Technologies that are capable of providing label-free, real-time insight into these interactions are of great value for the scientific and clin. communities. Greater understanding of biomol. interactions alongside increased detection accuracy can be achieved using technol. that can provide parallel information about multiple parameters of a single biomol. process. For example, electro-optical techniques combine optical and electrochem. information to provide more accurate and detailed measurements that provide unique insights into mol. structure and function. Here, we present a comparison of the main methods for electro-optical biosensing, namely, electrochem. surface plasmon resonance (EC-SPR), electrochem. optical waveguide lightmode spectroscopy (EC-OWLS), and the recently reported silicon-based electrophotonic approach. The comparison considers different application spaces, such as the detection of low concns. of biomols., integration, the tailoring of light-matter interaction for the understanding of biomol. processes, and 2D imaging of biointeractions on a surface.
- 16Bhalla, N.; Jolly, P.; Formisano, N.; Estrela, P. Introduction to Biosensors. Essays Biochem. 2016, 60, 1– 8, DOI: 10.1042/EBC20150001Google Scholar16https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2s7lvFCitw%253D%253D&md5=322bb5404ea09f2a2b4bd268a1c1780dIntroduction to biosensorsBhalla Nikhil; Jolly Pawan; Formisano Nello; Estrela PedroEssays in biochemistry (2016), 60 (1), 1-8 ISSN:.Biosensors are nowadays ubiquitous in biomedical diagnosis as well as a wide range of other areas such as point-of-care monitoring of treatment and disease progression, environmental monitoring, food control, drug discovery, forensics and biomedical research. A wide range of techniques can be used for the development of biosensors. Their coupling with high-affinity biomolecules allows the sensitive and selective detection of a range of analytes. We give a general introduction to biosensors and biosensing technologies, including a brief historical overview, introducing key developments in the field and illustrating the breadth of biomolecular sensing strategies and the expansion of nanotechnological approaches that are now available.
- 17Grieshaber, D.; MacKenzie, R.; Vörös, J.; Reimhult, E. Electrochemical Biosensors - Sensor Principles and Architectures. Sensors 2008, 8, 1400– 1458, DOI: 10.3390/s80314000Google Scholar17https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXkvVCrt7Y%253D&md5=7243bc3503b45588b401abdfa6021149Electrochemical biosensors - sensor principles and architecturesGrieshaber, Dorothee; MacKenzie, Robert; Voros, Janos; Reimhult, ErikSensors (2008), 8 (3), 1400-1458CODEN: SENSC9; ISSN:1424-8220. (Molecular Diversity Preservation International)A review. Quantification of biol. or biochem. processes are of utmost importance for medical, biol. and biotechnol. applications. However, converting the biol. information to an easily processed electronic signal is challenging due to the complexity of connecting an electronic device directly to a biol. environment. Electrochem. biosensors provide an attractive means to analyze the content of a biol. sample due to the direct conversion of a biol. event to an electronic signal. Over the past decades several sensing concepts and related devices have been developed. In this review, the most common traditional techniques, such as cyclic voltammetry, chronoamperometry, chronopotentiometry, impedance spectroscopy, and various field-effect transistor based methods are presented along with selected promising novel approaches, such as nanowire or magnetic nanoparticle-based biosensing. Addnl. measurement techniques, which have been shown useful in combination with electrochem. detection, are also summarized, such as the electrochem. versions of surface plasmon resonance, optical waveguide lightmode spectroscopy, ellipsometry, quartz crystal microbalance, and scanning probe microscopy. The signal transduction and the general performance of electrochem. sensors are often detd. by the surface architectures that connect the sensing element to the biol. sample at the nanometer scale. The most common surface modification techniques, the various electrochem. transduction mechanisms, and the choice of the recognition receptor mols. all influence the ultimate sensitivity of the sensor. New nanotechnol.-based approaches, such as the use of engineered ion-channels in lipid bilayers, the encapsulation of enzymes into vesicles, polymersomes, or polyelectrolyte capsules provide addnl. possibilities for signal amplification. In particular, this review highlights the importance of the precise control over the delicate interplay between surface nano-architectures, surface functionalization and the chosen sensor transducer principle, as well as the usefulness of complementary characterization tools to interpret and to optimize the sensor response.
- 18Kozma, P.; Kehl, F.; Ehrentreich-förster, E.; Stamm, C.; Bier, F. F. Integrated Planar Optical Waveguide Interferometer Biosensors: A Comparative Review. Biosens. Bioelectron. 2014, 58, 287– 307, DOI: 10.1016/j.bios.2014.02.049Google Scholar18https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXmsFGisLo%253D&md5=02729874ca8e0ff5065399ec57eff348Integrated planar optical waveguide interferometer biosensors: A comparative reviewKozma, Peter; Kehl, Florian; Ehrentreich-Foerster, Eva; Stamm, Christoph; Bier, Frank F.Biosensors & Bioelectronics (2014), 58 (), 287-307CODEN: BBIOE4; ISSN:0956-5663. (Elsevier B.V.)A review. Integrated planar optical waveguide interferometer biosensors are advantageous combinations of evanescent field sensing and optical phase difference measurement methods. By probing the near surface region of a sensor area with the evanescent field, any change of the refractive index of the probed vol. induces a phase shift of the guided mode compared to a ref. field typically of a mode propagating through the ref. arm of the same waveguide structure. The interfering fields of these modes produce an interference signal detected at the sensor's output, whose alteration is proportional to the refractive index change. This signal can be recorded, processed and related to e.g. the concn. of an analyte in the soln. of interest. Although this sensing principle is relatively simple, studies about integrated planar optical waveguide interferometer biosensors can mostly be found in the literature covering the past twenty years. During these two decades, several members of this sensor family have been introduced, which have remarkably advantageous properties. These entail label-free and non-destructive detection, outstandingly good sensitivity and detection limit, cost-effective and simple prodn., ability of multiplexing and miniaturization. Furthermore, these properties lead to low reagent consumption, short anal. time and open prospects for point-of-care applications. The present review collects the most relevant developments of the past twenty years categorizing them into two main groups, such as common- and double path waveguide interferometers. In addn., it tries to maintain the historical order as it is possible and it compares the diverse sensor designs in order to reveal not only the development of this field in time, but to contrast the advantages and disadvantages of the different approaches and sensor families, as well.
- 19Estevez, M. C.; Alvarez, M.; Lechuga, L. M. Integrated Optical Devices for Lab-on-a-Chip Biosensing Applications. Laser Photonics Rev. 2012, 6, 463– 487, DOI: 10.1002/lpor.201100025Google ScholarThere is no corresponding record for this reference.
- 20Chalyan, T.; Guider, R.; Pasquardini, L.; Zanetti, M.; Falke, F.; Schreuder, E.; Heideman, R. G.; Pederzolli, C.; Pavesi, L. Asymmetric Mach-Zehnder Interferometer Based Biosensors for Aflatoxin M1 Detection. Biosensors 2016, 6, 1– 10, DOI: 10.3390/bios6010001Google Scholar20https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXmtFemsrY%253D&md5=b189b049e0980be28ec5dbb06921c9e0Asymmetric Mach-Zehnder Interferometer based biosensors for Aflatoxin M1 detectionChalyan, Tatevik; Guider, Romain; Pasquardini, Laura; Zanetti, Manuela; Falke, Floris; Schreuder, Erik; Heideman, Rene G.; Pederzolli, Cecilia; Pavesi, LorenzoBiosensors (2016), 6 (1), 1/1-1/10CODEN: BIOSHU; ISSN:2079-6374. (MDPI AG)In this work, we present a study of Aflatoxin M1 detection by photonic biosensors based on Si3N4 Asym. Mach -Zehnder Interferometer (aMZI) functionalized with antibodies fragments (Fab'). We measured a best volumetric sensitivity of 104 rad/RIU, leading to a Limit of Detection below 5 10-7 RIU. On sensors functionalized with Fab', we performed specific and non-specific sensing measurements at various toxin concns. Reproducibility of the measurements and re-usability of the sensor were also investigated.
- 21Fernández-Gavela, A.; Herranz, S.; Chocarro, B.; Falke, F.; Schreuder, E.; Leeuwis, H.; Heideman, R. G.; Lechuga, L. M. Full Integration of Photonic Nanoimmunosensors in Portable Platforms for On-Line Monitoring of Ocean Pollutants. Sens. Actuators, B 2019, 297, 126758 DOI: 10.1016/j.snb.2019.126758Google Scholar21https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhtlKqtb3F&md5=f8d4757591f9fa2fe8467f1604c1d0f3Full integration of photonic nanoimmunosensors in portable platforms for on-line monitoring of ocean pollutantsFernandez-Gavela, Adrian; Herranz, Sonia; Chocarro, Blanca; Falke, Floris; Schreuder, Erik; Leeuwis, Henk; Heideman, Rene G.; Lechuga, Laura M.Sensors and Actuators, B: Chemical (2019), 297 (), 126758CODEN: SABCEB; ISSN:0925-4005. (Elsevier B.V.)A photonic nano-immunosensor platform for the on-site anal. of harmful org. ocean pollutants, intended to be allocated in stand-alone buoys was developed. The main aim was to bring the monitoring tools directly to the contaminated place, resulting in cost and time saving as compared to the std. anal. techniques. As sensor an integrated asym. Mach-Zehnder interferometer (aMZI) of micro/nano dimensions was employed, based on silicon photonic technol. In order to obtain a multiplexed system, a four-channel microfluidic cell was designed, manufd. and incorporated in the miniaturized sensor. Addnl., a microfluidic delivery module enabling automatic sample anal. was designed, evaluated and assembled. Moreover, the optical interconnections of the sensor chip was implemented by fiber optics, as well the electronics and the required software and data processing. Pollutant detection was based on a competitive immunoassay using bioreceptors previously biofunctionalized on the aMZI sensor arms and incubation with a specific antibody. As proof of concept, two types of pollutants were analyzed: the biocide Irgarol 1051, and the antibiotic Tetracycline. Results showed limits of detection in the range of few ng/mL, accomplished the European legislation.
- 22Heideman, R.; Hoekman, M.; Schreuder, E. TriPleX-Based Integrated Optical Ring Resonators for Lab-on-a-Chip and Environmental Detection. J. Sel. Top. Quantum Electron. 2012, 18, 1583– 1596, DOI: 10.1109/JSTQE.2012.2188382Google Scholar22https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhsFyitLfO&md5=30ef97b79efbb78c814647e44f104c53TriPleX-based integrated optical ring resonators for lab-on-a-chip and environmental detectionHeideman, Rene; Hoekman, Marcel; Schreuder, ErikIEEE Journal of Selected Topics in Quantum Electronics (2012), 18 (5), 1583-1596CODEN: IJSQEN; ISSN:1077-260X. (Institute of Electrical and Electronics Engineers)In this paper, we report exptl. results of integrated optics ring resonators (RRs) based on TriPleX waveguide technol. The RRs operate in the near IR enabling the use of very cost effective VCSELs as a light source. The exptl. obtained response of the ring resonators is in good agreement with theory, while the measured through and drop responses show very low on-chip losses. The chips show good coupling efficiencies to external fibers due to integrated spotsize converters. The corresponding signal-to-noise ratio enables for measurements of changes in refractive index (RI) smaller than 1 × 10-6 RIU. The RRs are combined with an 850-nm vertical-cavity surface-emitting laser (VCSEL) as a light source and prototype electronic equipment for signal processing. Several applications are described here, such as RI measurements in fluidic channels, label-free biochem. surface reactions, and gas detection in ambient atm.
- 23Gavela, A. F.; García, D. G.; Ramirez, J. C.; Lechuga, L. M. Last Advances in Silicon-Based Optical Biosensors. Sensors 2016, 16, 285 DOI: 10.3390/s16030285Google ScholarThere is no corresponding record for this reference.
- 24Bastos, A. R.; Vicente, C. M. S.; Oliveira-Silva, R.; Silva, N. J. O.; Tacão, M.; da Costa, J. P.; Lima, M.; André, P. S.; Ferreira, R. A. S. Integrated Optical Mach-Zehnder Interferometer Based on Organic-Inorganic Hybrids for Photonics-on-a-Chip Biosensing Applications. Sensors 2018, 18, 840 DOI: 10.3390/s18030840Google Scholar24https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXisVWgurzI&md5=a2eba6f052e346e25a93a13741dfdb7dIntegrated optical mach-zehnder interferometer based on organic-inorganic hybrids for photonics-on-a-chip biosensing applicationsBastos, Ana R.; Vicente, Carlos M. S.; Oliveira-Silva, Rui; Silva, Nuno J. O.; Tacao, Marta; da Costa, Joao P.; Lima, Mario; Andre, Paulo S.; Ferreira, Rute A. S.Sensors (2018), 18 (3), 840/1-840/11CODEN: SENSC9; ISSN:1424-8220. (MDPI AG)The development of portable low-cost integrated optics-based biosensors for photonics-on-a-chip devices for real-time diagnosis are of great interest, offering significant advantages over current anal. methods. We report the fabrication and characterization of an optical sensor based on a Mach-Zehnder interferometer to monitor the growing concn. of bacteria in a liq. medium. The device pattern was imprinted on transparent self-patternable org.-inorg. di-ureasil hybrid films by direct UV-laser, reducing the complexity and cost prodn. compared with lithog. techniques or three-dimensional (3D) patterning using femtosecond lasers. The sensor performance was evaluated using, as an illustrative example, E. coli cell growth in an aq. medium. The measured sensitivity (2 × 10-4 RIU) and limit of detection (LOD = 2 × 10-4) are among the best values known for low-refractive index contrast sensors. Furthermore, the di-ureasil hybrid used to produce this biosensor has addnl. advantages, such as mech. flexibility, thermal stability, and low insertion losses due to fiber-device refractive index mismatch (∼1.49). Therefore, the proposed sensor constitutes a direct, compact, fast, and cost-effective soln. for monitoring the concn. of lived-cells.
- 25Liu, Q.; Tu, X.; Woo, K.; Sheng, J.; Shin, Y.; Han, K.; Yoon, Y.; Lo, G.; Kyoung, M. Highly Sensitive Mach–Zehnder Interferometer Biosensor Based on Silicon Nitride Slot Waveguide. Sens. Actuators, B 2013, 188, 681– 688, DOI: 10.1016/j.snb.2013.07.053Google Scholar25https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhs1SgurfF&md5=de687567c1d18c24e9aaa13afea147f0Highly sensitive Mach-Zehnder interferometer biosensor based on silicon nitride slot waveguideLiu, Qing; Tu, Xiaoguang; Kim, Kyung Woo; Kee, Jack Sheng; Shin, Yong; Han, Kyungsup; Yoon, Yong-Jin; Lo, Guo-Qiang; Park, Mi KyoungSensors and Actuators, B: Chemical (2013), 188 (), 681-688CODEN: SABCEB; ISSN:0925-4005. (Elsevier B.V.)We demonstrate a highly sensitive label-free Mach-Zehnder interferometer (MZI) biosensor based on silicon nitride slot waveguide. Unlike the conventional MZI sensors, the sensing arm of the sensor consists of a slot waveguide while the ref. arm consists of a strip waveguide. Thanks to the slot waveguide's property to provide high optical intensity in a subwavelength-size low refractive index region (slot region), which allows high light-analyte interaction, higher sensitivity can be obtained as compared to conventional waveguides using the slot waveguide as sensing region. The bulk refractive index sensitivity of the slot waveguide MZI sensor was found to be 1864π/RIU (refractive index unit) with 7 mm long slot waveguide sensing arm, which shows higher sensitivity compared to the conventional MZI device based on silicon nitride. The biosensing capability of the developed slot waveguide MZI was investigated using biotin-streptavidin binding as a model system. The sensitivity of the system was demonstrated down to 18.9 fM or 1 pg/mL of streptavidin soln. and to the best of our knowledge, it is the best reported exptl. value for the limit of detection of a MZI sensor. Furthermore, we investigated the specific detection and quantification of the methylation of DAPK (Death-assocd. protein kinase) gene, which is a widely used biomarker for human cancers. We have shown that methylation sequences of DAPK gene of various methylation densities (100%, 50%, and 0% of methylation sites) can be quantified and discriminated even at a concn. as low as 1 fmol/μl or 1 nM.
- 26Psarouli, A.; Botsialas, A.; Salapatas, A.; Stefanitsis, G.; Nikita, D.; Jobst, G.; Chaniotakis, N.; Goustouridis, D.; Makarona, E.; Petrou, P. S. Fast Label-Free Detection of C-Reactive Protein Using Broad-Band Mach-Zehnder Interferometers Integrated on Silicon Chips. Talanta 2017, 165, 458– 465, DOI: 10.1016/j.talanta.2017.01.001Google Scholar26https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXntlehsg%253D%253D&md5=b8c20b6703144dc34152cc7d9eb93833Fast label-free detection of C-reactive protein using broad-band Mach-Zehnder interferometers integrated on silicon chipsPsarouli, Aimilia; Botsialas, Athanasios; Salapatas, Alexandros; Stefanitsis, Gerasimos; Nikita, Dimitra; Jobst, Gerhard; Chaniotakis, Nikolaos; Goustouridis, Dimitrios; Makarona, Eleni; Petrou, Panagiota S.; Raptis, Ioannis; Misiakos, Konstantinos; Kakabakos, Sotirios E.Talanta (2017), 165 (), 458-465CODEN: TLNTA2; ISSN:0039-9140. (Elsevier B.V.)An immunosensor for fast and accurate detn. of C-reactive protein (CRP) in human serum samples based on an array of all-silicon broad-band Mach-Zehnder interferometers (BB-MZIs) is demonstrated. The detection was based on monitoring the spectral shifts during the binding of CRP on the antibody mols. that have been immobilized on the sensing arms of the BB-MZIs. By employing the reaction rate as the anal. signal the assay time was compressed to few minutes. The detection limit was 2.1 ng/mL, the quantification limit was 4.2 ng/mL and the linear dynamic range extended up to 100 ng/mL. The measurements performed in human serum samples with the developed immunosensor were characterized by high repeatability and accuracy as it was demonstrated by diln. linearity and recovery expts. In addn., the concn. values detd. were in excellent agreement with those detd. for the same samples by a std. clin. lab. method. The compact size of the chip makes the proposed immunosensor attractive for incorporation into miniaturized devices for the detn. of clin. analytes at the point-of-need.
- 27Gauglitz, G.; Ingenhoff, J. Design of New Integrated Optical Substrates for Immuno-Analytical Applications. Fresenius’ J. Anal. Chem. 1994, 349, 355– 359, DOI: 10.1007/BF00326599Google Scholar27https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2cXlt12js70%253D&md5=23e81913db0fa08f97cf43944825b0ceDesign of new integrated optical substrates for immuno-analytical applicationsGauglitz, G.; Ingenhoff, J.Fresenius' Journal of Analytical Chemistry (1994), 349 (5), 355-9CODEN: FJACES; ISSN:0937-0633.Integrated optical Mach-Zehnder interferometers supply information on changes in refractive index and/or thickness of a film placed as a superstrate on top of one of its surface wave-guides. The internal propagation of light is influenced by the evanescent field reaching into the superstrate. This propagating light interferes with an uninfluenced wave in the second arm after recombination. The result is an intensity modulation depending on the refractive index parameters of the substrate, the waveguide itself and the properties of the superstrate. Taking an antigen layer as the superstrate, its interaction with antibodies changes its thickness by several nanometers. This can be obsd. by recording the change in intensity of the signal of the interferometer. The sensitivity of such a device depends on particular values of the optical parameters of substrate and waveguide with respect to the given superstrate properties. Computer calcns. help to select optimum glass and waveguide fabrication conditions. The numerical results of a variety of assumed conditions have been tested exptl. The application to the improved detection of triazines is discussed.
- 28Brosinger, F.; Freimuth, H.; Lacher, M.; Ehrfeld, W.; Gedig, E.; Katerkamp, A.; Spener, F.; Cammann, K. A Label-Free Affinity Sensor with Compensation of Unspecific Protein Interaction by a Highly Sensitive Integrated Optical Mach-Zehnder Interferometer on Silicon. Sens. Actuators, B 1997, 44, 350– 355, DOI: 10.1016/S0925-4005(97)00226-8Google Scholar28https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK1cXosFGnug%253D%253D&md5=18eabe5f89fc387ac72dc09869cb3c5fA label-free affinity sensor with compensation of unspecific protein interaction by a highly sensitive integrated optical Mach-Zehnder interferometer on siliconBrosinger, Franz; Freimuth, Herbert; Lacher, Manfred; Ehrfield, Wolfgang; Gedig, Erk; Katerkamp, Andreas; Spener, Friedrich; Cammann, KarlSensors and Actuators, B: Chemical (1997), 44 (1-3), 350-355CODEN: SABCEB; ISSN:0925-4005. (Elsevier Science S.A.)An integrated optical Mach-Zehnder interferometer (IO-MZI) on silicon was specially designed and tested for application as an affinity sensor. In order to obtain the necessary sensitivity, an optimization of the refractive index and the thickness of the wave-guiding layer was carried out. Refractive measurements with ethanol/water mixts. show a sensitivity of about one order of magnitude higher than the IO-MZIs previously described. The compensation of unspecific protein interaction in an affinity sensor set-up was demonstrated by using both branches of the IO-MZI. One branch was coated with a antigenic structure and sensor set-up was demonstrated by using both branches of the IO-MZI. One branch was coated with a antigenic structure and blocked with a protein mixt. whereas the other was only blocked. A sample with a high background of serum proteins was applied and only the sample contg. the specific antibody gave a measurable signal.
- 29Song, B.; Zhang, H.; Liu, B.; Lin, W.; Wu, J. Label-Free in-Situ Real-Time DNA Hybridization Kinetics Detection Employing Microfiber-Assisted Mach-Zehnder Interferometer. Biosens. Bioelectron. 2016, 81, 151– 158, DOI: 10.1016/j.bios.2016.02.065Google Scholar29https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XjsFKgu7c%253D&md5=f57f16586bae648c2bc1855c8e080cbdLabel-free in-situ real-time DNA hybridization kinetics detection employing microfiber-assisted mach-Zehnder interferometerSong, Binbin; Zhang, Hao; Liu, Bo; Lin, Wei; Wu, JixuanBiosensors & Bioelectronics (2016), 81 (), 151-158CODEN: BBIOE4; ISSN:0956-5663. (Elsevier B.V.)A label-free DNA biosensor based on microfiber-assisted Mach-Zehnder interferometer (MAMZI) for in-situ real-time DNA hybridization kinetics detection has been proposed and exptl. demonstrated. A microfiber of hundreds of microns in length is fabricated by tapering a segment of std. single-mode fiber (SMF) to construct the U-shaped microcavity between the lead-in and lead-out SMFs. Thanks to the mode field mismatching between the SMF and microfiber, the incident guided mode light would sep. into two beams that resp. propagate in the air microcavity and the microfiber. Consequently, interference between different light modes would occur at the joint between the microfiber and the lead-out SMF. Exptl. results indicate that owing to the participation of opening cavity modes in the modal interference process, the interferometric spectrum of our proposed microcavity sensor is highly sensitive to the variation of environmental refractive index (RI), esp. for the RI range around 1.34 which is useful for most biol. applications. The microfiber functionalization is achieved by stepwise modifying the microfiber with monolayer Poly-L-lysine (PLL) and single-stranded DNA (ssDNA) probes to produce the sensitive surface that could uniquely attach specific target ssDNAs. The fiber surface functionalization as well as DNA hybridization processes have been exptl. investigated for different target ssDNA solns. in real time. The interferometric transmission spectrum shows large wavelength shift for different biol. phases, and a detection limit conservatively down to 0.0001 pmol/μL has been acquired by employing the U-shaped microcavity of 176.88 μm in length. Our proposed DNA biosensor possesses several advantages such as compact size, ease of fabrication, and strong response for DNA hybridization, which make it a promising candidate for potential applications in such rapidly expanding areas as medical diagnosis, cancer screenings, medicine examn. and environmental engineering, etc.
- 30Movilli, J.; Rozzi, A.; Ricciardi, R.; Corradini, R.; Huskens, J. Control of Probe Density at DNA Biosensor Surfaces Using Poly-l-Lysine with Appended Reactive Groups. Bioconjugate Chem. 2018, 29, 4110– 4118, DOI: 10.1021/acs.bioconjchem.8b00733Google Scholar30https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXitFeku7%252FP&md5=5b63b9dd577f904a65d9542c11b4aa6dControl of Probe Density at DNA Biosensor Surfaces Using Poly(L-lysine) with Appended Reactive GroupsMovilli, Jacopo; Rozzi, Andrea; Ricciardi, Roberto; Corradini, Roberto; Huskens, JurriaanBioconjugate Chemistry (2018), 29 (12), 4110-4118CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)Biosensors and materials for biomedical applications generally require chem. functionalization to bestow their surfaces with desired properties, such as specific mol. recognition and antifouling properties. The use of modified poly(L-lysine) (PLL) polymers with appended oligo(ethylene glycol) (OEG) and thiol-reactive maleimide (Mal) moieties (PLL-OEG-Mal) offers control over the presentation of functional groups. These reactive groups can readily be conjugated to, for example, probes for DNA detection. Here we demonstrate the reliable conjugation of thiol-functionalized peptide nucleic acid (PNA) probes onto predeposited layers of PLL-OEG-Mal and the control over their surface d. in the preceding synthetic step of the PLL modification with Mal groups. By monitoring the quartz crystal microbalance (QCM) frequency shifts of the binding of complementary DNA vs. the d. of Mal moieties grafted to the PLL, a linear relationship between probe d. and PLL grafting d. was found. Cyclic voltammetry expts. using Methylene Blue-functionalized DNA were performed to establish the abs. probe d. values at the biosensor surfaces. These data provided a d. of 1.2 × 1012 probes per cm2 per % of grafted Mal, thus confirming the validity of the d. control in the synthetic PLL modification step without the need of further surface characterization.
- 31Di Iorio, D.; Marti, A.; Koeman, S.; Huskens, J. Clickable Poly-l-Lysine for the Formation of Biorecognition Surfaces. RSC Adv. 2019, 9, 35608– 35613, DOI: 10.1039/C9RA08714AGoogle Scholar31https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXitVygsb%252FM&md5=cab61dc322381a730fc643d237519527Clickable poly-L-lysine for the formation of biorecognition surfacesDi Iorio, Daniele; Marti, Almudena; Koeman, Sander; Huskens, JurriaanRSC Advances (2019), 9 (61), 35608-35613CODEN: RSCACL; ISSN:2046-2069. (Royal Society of Chemistry)Biomols. are immobilized onto surfaces employing the fast and stable adsorption of poly-L-lysine (PLL) polymers and the versatile copper-free click chem. reactions. This method provides the combined advantages of versatile surface adsorption with d. control using polyelectrolytes and of the covalent and orthogonal immobilization of biomols. with higher reaction rates and improved yields of click chem. Using DNA attachment as a proof of concept, control over the DNA probe d. and applicability in electrochem. detection are presented.
- 32Sauerbrey, G. Verwendung von Schwingquarzen Zur Wägung Dünner Schichten Und Zur Mikrowägung. Z. Phys. 1959, 155, 206– 222, DOI: 10.1007/BF01337937Google Scholar32https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaG1MXoslSjtQ%253D%253D&md5=ff97a9cc63637eb9823aebfeb57a367bThe use of quartz oscillators for weighing thin layers and for microweighingSauerbrey, GuntherZeitschrift fuer Physik (1959), 155 (), 206-22CODEN: ZEPYAA; ISSN:0044-3328.The frequency of a quartz plate is altered if a layer of foreign material is deposited on the quartz, e.g. by evapn. Since changes in frequency can be measured very accurately, the phenomenon can be used for weighing thin layers. The change in frequency is proportional to the d. of the foreign layer and the proportionality const. can be calcd. from the characteristic frequency of the quartz plate. The accuracy of the method is limited by the temp. variation of the characteristic frequency of the quartz oscillator. For a temp. fluctuation of 1° the accuracy is ±4.10-9 g./cm. This corresponds to a mean thickness of the layer of 0.4 A. at a d. of 1 g./cc. The method can also be used for direct microweighing, e.g. by evapg. a drop of a soln. on the quartz plate.
- 33Larsson, C.; Rodahl, M.; Höök, F. Characterization of DNA Immobilization and Subsequent Hybridization on a 2D Arrangement of Streptavidin on a Biotin-Modified Lipid Bilayer Supported on SiO2. Anal. Chem. 2003, 75, 5080– 5087, DOI: 10.1021/ac034269nGoogle Scholar33https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXms1aqsbY%253D&md5=90361694a37d1e2314cab0865ef2c656Characterization of DNA immobilization and subsequent hybridization on a 2D arrangement of streptavidin on a biotin-modified lipid bilayer supported on SiO2Larsson, Charlotte; Rodahl, Michael; Hoeoek, FredrikAnalytical Chemistry (2003), 75 (19), 5080-5087CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)We show how the water content (and effective d.) of thin adsorbed films composed of biomols. can be detd. using combined quartz crystal microbalance with dissipation monitoring (QCM-D) and surface plasmon resonance (SPR) anal. In particular, these techniques, combined with theor. treatment using a Voigt-based viscoelastic model, were applied to analyze the state of surface immobilized single stranded biotin-modified probe DNA (b-DNA) coupled via streptavidin to a biotin-doped supported phospholipid bilayer (b-SPB). From a proper anal., it is demonstrated how changes in effective thickness, δf, and the viscoelastic components (shear viscosity, ηf, and shear elasticity, μf) can be obtained during both DNA immobilization and hybridization with single stranded fully complementary target DNA. In particular, it is demonstrated how this type of anal. can be used to control the state of streptavidin arrangement for improved measurements of DNA hybridization kinetics. The latter is demonstrated by identifying a surface-coverage dependent viscoelastic behavior of immobilized b-DNA, which is shown to influence the hybridization efficiency.
- 34Seifert, M.; Rinke, M. T.; Galla, H. J. Characterization of Streptavidin Binding to Biotinylated, Binary Self-Assembled Thiol Monolayers - Influence of Component Ratio and Solvent.. Langmuir 2010, 26, 6386– 6393, DOI: 10.1021/la904087sGoogle Scholar34https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhvFKhsr8%253D&md5=a9ba964b7d4170d369a90b060632efa9Characterization of Streptavidin Binding to Biotinylated, Binary Self-Assembled Thiol Monolayers - Influence of Component Ratio and SolventSeifert, Michael; Rinke, Matthias T.; Galla, Hans-JoachimLangmuir (2010), 26 (9), 6386-6393CODEN: LANGD5; ISSN:0743-7463. (American Chemical Society)Many biosensor applications are based on streptavidin (SA) binding to partially biotinylated self-assembled thiol monolayers (SAMs). In the authors' study, binary SAMs on gold were prepd. from solns. contg. 16-mercapto-1-hexadecanol (thiol I) and N-(8-biotinyl-3,6-dioxa-octanamidyl)-16-mercaptohexadecanamide (thiol II) in varying component ratios. Either chloroform or ethanol was used as solvent. After 24 h thiol incubation, SA was immobilized on the resulting SAMs using the strong SA-biotin interaction. The SA binding process was monitored by QCM-D (quartz crystal microbalance monitoring dissipation factor). It is shown that the Sauerbrey equation is valid to calc. the mass quantities of the immobilized SA layers. Under the chosen incubation conditions, marginal fractions of the biotinylated component II in chloroform ((nI/nII)solution ≈ 1000) lead to SAMs which ensure a maximal SA binding quantity of mSauerbrey SA ≈ 400 ng/cm-2, being equiv. to a SA single-layer arrangement on the SAM surface. In case of incubations from ethanolic solns., a complete SA layer formation needs significantly higher amts. of the biotinylated component II during SAM prepn. ((nI/nII)solution ≈ 50). XPS data show that the fraction of biotinylated thiol II in the SAM dets. the amt. of surface-bound SA. The SAM thiol ratio ((nI/nII)SAM) not only depends on the corresponding component ratio in the incubation soln., but is also strongly influenced by the solvent. Using chloroform as solvent during SAM prepn. significantly increased the fraction of biotinylated thiol II in the SAMs compared to ethanol.
- 35Vogt, B. D.; Soles, C. L.; Lee, H. J.; Lin, E. K.; Wu, W. L. Moisture Absorption and Absorption Kinetics in Polyelectrolyte Films: Influence of Film Thickness. Langmuir 2004, 20, 1453– 1458, DOI: 10.1021/la035239iGoogle Scholar35https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXjslaiug%253D%253D&md5=4f1ba3c81a9df7467efd40b749ddd64eMoisture Absorption and Absorption Kinetics in Polyelectrolyte Films: Influence of Film ThicknessVogt, Bryan D.; Soles, Christopher L.; Lee, Hae-Jeong; Lin, Eric K.; Wu, Wen-liLangmuir (2004), 20 (4), 1453-1458CODEN: LANGD5; ISSN:0743-7463. (American Chemical Society)Specular X-ray reflectivity (XR) and quartz crystal microbalance (QCM) measurements were used to det. the absorption of water into thin poly(ammonium 4-styrenesulfonic acid) films from satd. vapor at 25 °C. The effect of film thickness on the absorption kinetics and overall absorption was investigated in the range of thickness from (3 to 200) nm. The equil. swelling of all the films irresp. of film thickness was (0.57 ± 0.03) vol. fraction. Although the equil. absorption is independent of thickness, the absorption rate substantially decreases for film thickness < 100 nm. For the thinnest film (3 nm), there is a 5 orders of magnitude decrease in the diffusion coeff. for water.
- 36Besselink, G. A. J.; Heideman, R. G.; Schreuder, E.; Wevers, L. S.; Falke, F.; van den Vlekkert, H. H. Performance of Arrayed Microring Resonator Sensors with the TriPleX Platform. J. Biosens. Bioelectron. 2016, 7, 1000209 DOI: 10.4172/2155-6210.1000209Google ScholarThere is no corresponding record for this reference.
- 37Duan, X.; Mu, L.; Sawtelle, S. D.; Rajan, N. K.; Han, Z.; Wang, Y.; Qu, H.; Reed, M. A. Functionalized Polyelectrolytes Assembling on Nano-BioFETs for Biosensing Applications. Adv. Funct. Mater. 2015, 25, 2279– 2286, DOI: 10.1002/adfm.201500002Google Scholar37https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXkvF2gtb0%253D&md5=3b2c1c95f9423fecb79aba5632a93092Functionalized Polyelectrolytes Assembling on Nano-BioFETs for Biosensing ApplicationsDuan, Xuexin; Mu, Luye; Sawtelle, Sonya D.; Rajan, Nitin K.; Han, Ziyu; Wang, Yanyan; Qu, Hemi; Reed, Mark A.Advanced Functional Materials (2015), 25 (15), 2279-2286CODEN: AFMDC6; ISSN:1616-301X. (Wiley-VCH Verlag GmbH & Co. KGaA)A new surface functionalization scheme for nano-Bio field effect transistors (FETs) using biocompatible polyelectrolyte thin films (PET) is developed. PET assemblies on Si nanowires (Si-NWs) are driven by electrostatic interactions between the pos. charged polymer backbone and neg. charged Si/SiO2 surface. Such assemblies can be directly coated from PET aq. solns. and result in a uniform nanoscale thin film, which is more stable compared to the conventional amine silanization. Short oligo-ethylene glycol chains are grafted on the PETs to prevent nonspecific protein binding. Moreover, the reactive groups of the polymer chains can be further functionalized to other chem. groups in specific stoichiometry for biomols. detection. Therefore, it opens a new strategy to precisely control the functional group densities on various biosensor surfaces at the mol. level. In addn., such assemblies of the polymers together with the bound analytes can be removed with the pH stimulation resulting in regeneration of a bare sensor surface without compromising the integrity and performance of the Si-NWs. Thus, it is believed that the developed PET coating and sensing systems on Si-NW FETs represent a versatile, promising approach for regenerative biosensors which can be applied to other biosensors and will benefit real device applications, enhancing sensor lifetime, reliability, and repeatability.
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Abstract
Figure 1
Figure 1. Photograph of an aMZI chip with lithographically defined Si3N4 waveguides showing the six parallel aMZI devices (arranged top to bottom). Each aMZI device consists of a reference channel (left), which is closed (covered by SiO2), and an analyte channel (right), which is open to the flow of liquids.
Figure 2
Figure 2. (a) Schematic of the adsorption of PLL-biotin and PLL-OEG, and the subsequent binding of streptavidin to the biotin moieties. (b) Structures of PLL-OEG (left) and PLL-biotin (right).
Figure 3
Figure 3. QCM-D (frequency, left axis, and dissipation, right axis) data of increasing concentrations of streptavidin (values given in the graph; buffer flow when no concentration is given) at substrates coated with (a) PLL-OEG and (b) PLL-biotin.
Figure 4
Figure 4. aMZI data showing the binding of streptavidin (values given in the graph; buffer flow when no concentration is given) to PLL-biotin: (a) raw data and (b) data with reference subtracted.
Figure 5
Figure 5. Photograph of the aMZI setup with the fluidic system and the piezoelectric auto-alignment stage.
References
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- 3Neethirajan, S.; Ragavan, V.; Weng, X.; Chand, R. Biosensors for Sustainable Food Engineering: Challenges and Perspectives. Biosensors 2018, 8, 23 DOI: 10.3390/bios80100233https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhsVKmt7%252FM&md5=d19b62f44ad958fe23083f8bfe7b5925Biosensors for sustainable food engineering: challenges and perspectivesNeethirajan, Suresh; Ragavan, Vasanth; Weng, Xuan; Chand, RohitBiosensors (2018), 8 (1), 23/1-23/34CODEN: BIOSHU; ISSN:2079-6374. (MDPI AG)Current food prodn. faces tremendous challenges from growing human population, maintaining clean resources and food qualities, and protecting climate and environment. Food sustainability is mostly a cooperative effort resulting in technol. development supported by both governments and enterprises. Multiple attempts have been promoted in tackling challenges and enhancing drivers in food prodn. Biosensors and biosensing technologies with their applications, are being widely applied to tackling top challenges in food prodn. and its sustainability. Consequently, a growing demand in biosensing technologies exists in food sustainability. Microfluidics represents a technol. system integrating multiple technologies. Nanomaterials, with its technol. in biosensing, is thought to be the most promising tool in dealing with health, energy, and environmental issues closely related to world populations. The demand of point of care (POC) technologies in this area focus on rapid, simple, accurate, portable, and low-cost anal. instruments. This review provides current viewpoints from the literature on biosensing in food prodn., food processing, safety and security, food packaging and supply chain, food waste processing, food quality assurance, and food engineering. The current understanding of progress, soln., and future challenges, as well as the commercialization of biosensors are summarized.
- 4Yoo, E. H.; Lee, S. Y. Glucose Biosensors: An Overview of Use in Clinical Practice. Sensors 2010, 10, 4558– 4576, DOI: 10.3390/s1005045584https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC383ps1Wgsg%253D%253D&md5=cfcc8dd4d944e63a772f3c181314e37bGlucose biosensors: an overview of use in clinical practiceYoo Eun-Hyung; Lee Soo-YounSensors (Basel, Switzerland) (2010), 10 (5), 4558-76 ISSN:.Blood glucose monitoring has been established as a valuable tool in the management of diabetes. Since maintaining normal blood glucose levels is recommended, a series of suitable glucose biosensors have been developed. During the last 50 years, glucose biosensor technology including point-of-care devices, continuous glucose monitoring systems and noninvasive glucose monitoring systems has been significantly improved. However, there continues to be several challenges related to the achievement of accurate and reliable glucose monitoring. Further technical improvements in glucose biosensors, standardization of the analytical goals for their performance, and continuously assessing and training lay users are required. This article reviews the brief history, basic principles, analytical performance, and the present status of glucose biosensors in the clinical practice.
- 5Khanmohammadi, A.; Aghaie, A.; Vahedi, E.; Qazvini, A.; Ghanei, M.; Afkhami, A.; Hajian, A.; Bagheri, H. Electrochemical Biosensors for the Detection of Lung Cancer Biomarkers: A Review. Talanta 2020, 206, 120251 DOI: 10.1016/j.talanta.2019.1202515https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhsF2msb7L&md5=84f559a8344e3839fd6e976b67dd439cElectrochemical biosensors for the detection of lung cancer biomarkers: A reviewKhanmohammadi, Akbar; Aghaie, Ali; Vahedi, Ensieh; Qazvini, Ali; Ghanei, Mostafa; Afkhami, Abbas; Hajian, Ali; Bagheri, HasanTalanta (2020), 206 (), 120251CODEN: TLNTA2; ISSN:0039-9140. (Elsevier B.V.)A review. Cancer is one of the most widespread challenges and important diseases, which has the highest mortality rate. Lung cancer is the most common type of cancer, so that ∼25% of all cancer deaths are related to the lung cancer. The lung cancer is classified as two different types with different treatment methodol.: the small cell lung carcinoma and nonsmall cell lung carcinoma are two categories of the lung cancer. Since the lung cancer is often in the latent period in its early stages, therefore, early diagnosis of lung cancer has many challenges. Hence, there is a need for sensitive and reliable tools for preclin. diagnosis of lung cancer. Therefore, many detection methods have been employed for early detection of lung cancer. As lung cancer tumors growth in the body, the cancerous cells release numerous DNA, proteins, and metabolites as special biomarkers of the lung cancer. The levels of these biomarkers show the stages of the lung cancer. Therefore, detection of the biomarkers can be used for screening and clin. diagnosis of the lung cancer. There are numerous biomarkers for the lung cancer such as EGFR, CEA, CYFRA 21-1, ENO1, NSE, CA 19-9, CA 125 and VEGF. Nowadays, electrochem. methods are very attractive and useful in the lung cancer detections. So, the recent advances and improvements (2010-2018) in the electrochem. detection of the lung cancer biomarkers have been reviewed.
- 6Qian, L.; Li, Q.; Baryeh, K.; Qiu, W.; Li, K.; Zhang, J.; Yu, Q.; Xu, D.; Liu, W.; Brand, R. E. Biosensors for Early Diagnosis of Pancreatic Cancer: A Review. Transl. Res. 2019, 213, 67– 89, DOI: 10.1016/j.trsl.2019.08.0026https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhs1WisL7N&md5=9f74ee2b04e7feb57c0e40bf58c700b5Biosensors for early diagnosis of pancreatic cancer: a reviewQian, Lisheng; Li, Qiaobin; Baryeh, Kwaku; Qiu, Wanwei; Li, Kun; Zhang, Jing; Yu, Qingcai; Xu, Dongqin; Liu, Wenju; Brand, Randall E.; Zhang, Xueji; Chen, Wei; Liu, GuodongTranslational Research (2019), 213 (), 67-89CODEN: TRRECL; ISSN:1878-1810. (Elsevier B.V.)A review. Pancreatic cancer is characterized by extremely high mortality and poor prognosis and is projected to be the leading cause of cancer deaths by 2030. Due to the lack of early symptoms and appropriate methods to detect pancreatic carcinoma at an early stage as well as its aggressive progression, the disease is often quite advanced by the time a definite diagnosis is established. The 5-yr relative survival rate for all stages is approx. 8%. Therefore, detection of pancreatic cancer at an early surgically resectable stage is the key to decrease mortality and to improve survival. The traditional methods for diagnosing pancreatic cancer involve an imaging test, such as ultrasound or magnetic resonance imaging, paired with a biopsy of the mass in question. These methods are often expensive, time consuming, and require trained professionals to use the instruments and analyze the imaging. To overcome these issues, biosensors have been proposed as a promising tool for the early diagnosis of pancreatic cancer. The present critically discusses the latest developments in biosensors for the early diagnosis of pancreatic cancer. Protein and microRNA biomarkers of pancreatic cancer and corresponding biosensors for pancreatic cancer diagnosis have been ed, and all these cases demonstrate that the emerging biosensors are becoming an increasingly relevant alternative to traditional techniques. In addn., we discuss the existing problems in biosensors and future challenges.
- 7Sanati, A.; Jalali, M.; Raeissi, K.; Karimzadeh, F.; Kharaziha, M.; Mahshid, S. S.; Mahshid, S. A Review on Recent Advancements in Electrochemical Biosensing Using Carbonaceous Nanomaterials. Microchim. Acta 2019, 186, 773 DOI: 10.1007/s00604-019-3854-27https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXitFKrsb3I&md5=2c4aed6e2ccb9bba62f152a8329499c9A review on recent advancements in electrochemical biosensing using carbonaceous nanomaterialsSanati, Alireza; Jalali, Mahsa; Raeissi, Keyvan; Karimzadeh, Fathallah; Kharaziha, Mahshid; Mahshid, Sahar Sadat; Mahshid, SaraMicrochimica Acta (2019), 186 (12), 773CODEN: MIACAQ; ISSN:0026-3672. (Springer-Verlag GmbH)This review, with 201 refs., describes the recent advancement in the application of carbonaceous nanomaterials as highly conductive platforms in electrochem. biosensing. The electrochem. biosensing is described in introduction by classifying biosensors into catalytic-based and affinity-based biosensors and statistically demonstrates the most recent published works in each category. The introduction is followed by sections on electrochem. biosensors configurations and common carbonaceous nanomaterials applied in electrochem. biosensing, including graphene and its derivs., carbon nanotubes, mesoporous carbon, carbon nanofibers and carbon nanospheres. In the following sections, carbonaceous catalytic-based and affinity-based biosensors are discussed in detail. In the category of catalytic-based biosensors, a comparison between enzymic biosensors and non-enzymic electrochem. sensors is carried out. Regarding the affinity-based biosensors, scholarly articles related to biol. elements such as antibodies, DNAs (DNAs) and aptamers are discussed in sep. sections. The last section discusses recent advancements in carbonaceous screen-printed electrodes as a growing field in electrochem. biosensing. Tables are presented that give an overview on the diversity of analytes, type of materials and the sensors performance. Ultimately, general considerations, challenges and future perspectives in this field of science are discussed. Recent findings suggest that interests towards 2D nanostructured electrodes based on graphene and its derivs. are still growing in the field of electrochem. biosensing. That is because of their exceptional elec. cond., active surface area and more convenient prodn. methods compared to carbon nanotubes. [Figure not available: see fulltext.].
- 8Blair, E. O.; Corrigan, D. K. A Review of Microfabricated Electrochemical Biosensors for DNA Detection. Biosens. Bioelectron. 2019, 134, 57– 67, DOI: 10.1016/j.bios.2019.03.0558https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXmvFSnu74%253D&md5=38386a96b0e01854791460963cbb5464A review of microfabricated electrochemical biosensors for DNA detectionBlair, Ewen O.; Corrigan, Damion K.Biosensors & Bioelectronics (2019), 134 (), 57-67CODEN: BBIOE4; ISSN:0956-5663. (Elsevier B.V.)This review article presents an overview of recent work on electrochem. biosensors developed using microfabrication processes, particularly sensors used to achieve sensitive and specific detection of DNA sequences. Such devices are important as they lend themselves to miniaturization, reproducible mass-manuf., and integration with other previously existing technologies and prodn. methods. The review describes the current state of these biosensors, novel methods used to produce them or enhance their sensing properties, and pathways to deployment of a complete point-of-care biosensing system in a clin. setting.
- 9Batool, R.; Rhouati, A.; Nawaz, M. H.; Hayat, A.; Marty, J. L. A Review of the Construction of Nano-Hybrids for Electrochemical Biosensing of Glucose. Biosensors 2019, 9, 46 DOI: 10.3390/bios90100469https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXisVGru7bE&md5=3b6d1879d8b2eb77b68f75a3e6029bb2A review of the construction of nano-hybrids for electrochemical biosensing of glucoseBatool, Razia; Rhouati, Amina; Nawaz, Mian Hasnain; Hayat, Akhtar; Marty, Jean LouisBiosensors (2019), 9 (1), 46CODEN: BIOSHU; ISSN:2079-6374. (MDPI AG)Continuous progress in the domain of nano and material science has led to modulation of the properties of nanomaterials in a controlled and desired fashion. In this sense, nanomaterials, including carbon-based materials, metals and metal oxides, and composite/hybrid materials have attracted extensive interest with regard to the construction of electrochem. biosensors. The modification of a working electrode with a combination of two or three nanomaterials in the form of nano-composite/nano-hybrids has revealed good results with very good reproducibility, stability, and improved sensitivity. This review paper is focused on discussing the possible constructs of nano-hybrids and their subsequent use in the construction of electrochem. glucose biosensors.
- 10Wang, W.; Su, H.; Wu, Y.; Zhou, T.; Li, T. Review-Biosensing and Biomedical Applications of Graphene: A Review of Current Progress and Future Prospect. J. Electrochem. Soc. 2019, 166, B505– B520, DOI: 10.1149/2.1231906jes10https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXpvFSltbk%253D&md5=7e099789cee74c6b66bc716ef3b1a831Review-biosensing and biomedical applications of graphene: a review of current progress and future prospectWang, Weiran; Su, Hengjie; Wu, Yuxiang; Zhou, Teng; Li, TingJournal of the Electrochemical Society (2019), 166 (6), B505-B520CODEN: JESOAN; ISSN:0013-4651. (Electrochemical Society)Graphene has generated widely interest in biosensor study because it had a large surface area, excellent elec. and thermal cond., high mech. strength and other unique phys. and chem. properties. In this paper, graphene was reviewed from three aspects. Firstly, several common fabrication methods and characteristics of graphene were introduced. Secondly, applications of the nanosized graphene (NG) and nanosized graphene oxide (NGO) in biosensor and medical imaging were discussed. The NG and NGO had the characteristics of photoluminescence. Based on the fluorescence quenching nature of the graphene surface, the targeting mols. could be confirmed by detecting the fluorescent substance. In addn., the graphene oxide (GO) had a promising prospect in the field of surface-enhanced Raman imaging. In the field of electrochem., graphene and its derivs. could be modified on the surface to couple with ligands and antigens and were able to detect specific biomols., such as glucose, DNA, proteins and etc. Thirdly, this paper introduced graphene applications in medical treatment. Due to the inherent high near-IR (NIR) absorbance, graphene materials were widely used in the treatment of in vivo cancer photothermal therapy. The combination of the graphene, anticancer drugs, and specific antigens was highly efficient for drug delivery. This paper summarized the achievements of graphene materials in the medical diagnostics, the presents challenges, and the future prospect.
- 11Syu, Y. C.; Hsu, W. E.; Lin, C. T. Review-Field-Effect Transistor Biosensing: Devices and Clinical Applications. ECS J. Solid State Sci. Technol. 2018, 7, Q3196– Q3207, DOI: 10.1149/2.0291807jss11https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhsVKju73J&md5=21c12f2b74737b49e7bc2d84288e092fReview-Field-Effect Transistor Biosensing: Devices and Clinical ApplicationsSyu, Yu-Cheng; Hsu, Wei-En; Lin, Chih-TingECS Journal of Solid State Science and Technology (2018), 7 (7), Q3196-Q3207CODEN: EJSSBG; ISSN:2162-8769. (Electrochemical Society)A review. Biosensor research has been addressed as an interested field recently. Within different kinds of developed biosensing technologies, field-effect transistor (FET) based biosensors stand out due to their attractive features, such as ultra-sensitivity detection, mass-prodn. capability, and low-cost manufg. To promote understandings of the FET based biosensing technol., in this review, its sensing mechanism is introduced, as well as major FET-based biosensing devices: ion sensitive field-effect transistor (ISFET), silicon nanowire, org. FET, graphene FET, and compd.-semiconductor FET. In addn. to FET-based biosensing devices, clin. applications, such as cardiovascular diseases (CVDs), cancers, diabetes, HIV, and DNA sequence, are also reviewed. In the end, several crit. challenges of FET-based biosensing technol. are discussed to envision next steps in healthcare technologies.
- 12Garzón, V.; Pinacho, D. G.; Bustos, R. H.; Garzón, G.; Bustamante, S. Optical Biosensors for Therapeutic Drug Monitoring. Biosensors 2019, 9, 132 DOI: 10.3390/bios904013212https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtFOgtbzJ&md5=c6097c01de834ab022d21a603d7db7fcOptical biosensors for therapeutic drug monitoringGarzon, Vivian; Pinacho, Daniel G.; Bustos, Rosa-Helena; Garzon, Gustavo; Bustamante, SandraBiosensors (2019), 9 (4), 132CODEN: BIOSHU; ISSN:2079-6374. (MDPI AG)Therapeutic drug monitoring (TDM) is a fundamental tool when administering drugs that have a limited dosage or high toxicity, which could endanger the lives of patients. To carry out this monitoring, one can use different biol. fluids, including blood, plasma, serum, and urine, among others. The help of specialized methodologies for TDM will allow for the pharmacodynamic and pharmacokinetic anal. of drugs and help adjust the dose before or during their administration. Techniques that are more versatile and label free for the rapid quantification of drugs employ biosensors, devices that consist of one element for biol. recognition coupled to a signal transducer. Among biosensors are those of the optical biosensor type, which have been used for the quantification of different mols. of clin. interest, such as antibiotics, anticonvulsants, anti-cancer drugs, and heart failure. This review presents an overview of TDM at the global level considering various aspects and clin. applications. In addn., we review the contributions of optical biosensors to TDM.
- 13Mejía-Salazar, J. R.; Oliveira, O. N. Plasmonic Biosensing. Chem. Rev. 2018, 118, 10617– 10625, DOI: 10.1021/acs.chemrev.8b0035913https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhslKhtrbP&md5=33112eac9bdb55911c28aa95b098bb8ePlasmonic BiosensingMejia-Salazar, J. R.; Oliveira, Osvaldo N.Chemical Reviews (Washington, DC, United States) (2018), 118 (20), 10617-10625CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review. Plasmonic biosensing has been used for fast, real-time, and label-free probing of biol. relevant analytes, where the main challenges are to detect small mols. at ultralow concns. and produce compact devices for point-of-care (PoC) anal. This review discusses the most recent, or even emerging, trends in plasmonic biosensing, with novel platforms which exploit unique physicochem. properties and versatility of new materials. In addn. to the well-established use of localized surface plasmon resonance (LSPR), three major areas have been identified in these new trends: chiral plasmonics, magnetoplasmonics, and quantum plasmonics. In describing the recent advances, emphasis is placed on the design and manuf. of portable devices working with low loss in different frequency ranges, from the IR to the visible.
- 14Peltomaa, R.; Glahn-Martínez, B.; Benito-Peña, E.; Moreno-Bondi, M. C. Optical Biosensors for Label-Free Detection of Small Molecules. Sensors 2018, 18, 4126 DOI: 10.3390/s1812412614https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhtFagtLzN&md5=8567f91fe7042dc59217b37f021ab506Optical biosensors for label-free detection of small moleculesPeltomaa, Riikka; Glahn-Martinez, Bettina; Benito-Pena, Elena; Moreno-Bondi, Maria C.Sensors (2018), 18 (12), 4126/1-4126/46CODEN: SENSC9; ISSN:1424-8220. (MDPI AG)A review. Label-free optical biosensors are an intriguing option for the analyses of many analytes, as they offer several advantages such as high sensitivity, direct and real-time measurement in addn. to multiplexing capabilities. However, development of label-free optical biosensors for small mols. can be challenging as most of them are not naturally chromogenic or fluorescent, and in some cases, the sensor response is related to the size of the analyte. To overcome some of the limitations assocd. with the anal. of biol., pharmacol., or environmentally relevant compds. of low mol. wt., recent advances in the field have improved the detection of these analytes using outstanding methodol., instrumentation, recognition elements, or immobilization strategies. In this review, we aim to introduce some of the latest developments in the field of label-free optical biosensors with the focus on applications with novel innovations to overcome the challenges related to small mol. detection. Optical label-free methods with different transduction schemes, including evanescent wave and optical fiber sensors, surface plasmon resonance, surface-enhanced Raman spectroscopy, and interferometry, using various biorecognition elements, such as antibodies, aptamers, enzymes, and bioinspired molecularly imprinted polymers, are reviewed.
- 15Juan-Colás, J.; Johnson, S.; Krauss, T. F. Dual-Mode Electro-Optical Techniques for Biosensing Applications: A Review. Sensors 2017, 17, 2047 DOI: 10.3390/s1709204715https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXkt1Cnu7s%253D&md5=8011b1fc0f3ea29f48fd8b35969635ecDual-mode electro-optical techniques for biosensing applications: a reviewJuan-Colas, Jose; Johnson, Steven; Krauss, Thomas F.Sensors (2017), 17 (9), 2047/1-2047/15CODEN: SENSC9; ISSN:1424-8220. (MDPI AG)The monitoring of biomol. interactions is a key requirement for the study of complex biol. processes and the diagnosis of disease. Technologies that are capable of providing label-free, real-time insight into these interactions are of great value for the scientific and clin. communities. Greater understanding of biomol. interactions alongside increased detection accuracy can be achieved using technol. that can provide parallel information about multiple parameters of a single biomol. process. For example, electro-optical techniques combine optical and electrochem. information to provide more accurate and detailed measurements that provide unique insights into mol. structure and function. Here, we present a comparison of the main methods for electro-optical biosensing, namely, electrochem. surface plasmon resonance (EC-SPR), electrochem. optical waveguide lightmode spectroscopy (EC-OWLS), and the recently reported silicon-based electrophotonic approach. The comparison considers different application spaces, such as the detection of low concns. of biomols., integration, the tailoring of light-matter interaction for the understanding of biomol. processes, and 2D imaging of biointeractions on a surface.
- 16Bhalla, N.; Jolly, P.; Formisano, N.; Estrela, P. Introduction to Biosensors. Essays Biochem. 2016, 60, 1– 8, DOI: 10.1042/EBC2015000116https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2s7lvFCitw%253D%253D&md5=322bb5404ea09f2a2b4bd268a1c1780dIntroduction to biosensorsBhalla Nikhil; Jolly Pawan; Formisano Nello; Estrela PedroEssays in biochemistry (2016), 60 (1), 1-8 ISSN:.Biosensors are nowadays ubiquitous in biomedical diagnosis as well as a wide range of other areas such as point-of-care monitoring of treatment and disease progression, environmental monitoring, food control, drug discovery, forensics and biomedical research. A wide range of techniques can be used for the development of biosensors. Their coupling with high-affinity biomolecules allows the sensitive and selective detection of a range of analytes. We give a general introduction to biosensors and biosensing technologies, including a brief historical overview, introducing key developments in the field and illustrating the breadth of biomolecular sensing strategies and the expansion of nanotechnological approaches that are now available.
- 17Grieshaber, D.; MacKenzie, R.; Vörös, J.; Reimhult, E. Electrochemical Biosensors - Sensor Principles and Architectures. Sensors 2008, 8, 1400– 1458, DOI: 10.3390/s8031400017https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXkvVCrt7Y%253D&md5=7243bc3503b45588b401abdfa6021149Electrochemical biosensors - sensor principles and architecturesGrieshaber, Dorothee; MacKenzie, Robert; Voros, Janos; Reimhult, ErikSensors (2008), 8 (3), 1400-1458CODEN: SENSC9; ISSN:1424-8220. (Molecular Diversity Preservation International)A review. Quantification of biol. or biochem. processes are of utmost importance for medical, biol. and biotechnol. applications. However, converting the biol. information to an easily processed electronic signal is challenging due to the complexity of connecting an electronic device directly to a biol. environment. Electrochem. biosensors provide an attractive means to analyze the content of a biol. sample due to the direct conversion of a biol. event to an electronic signal. Over the past decades several sensing concepts and related devices have been developed. In this review, the most common traditional techniques, such as cyclic voltammetry, chronoamperometry, chronopotentiometry, impedance spectroscopy, and various field-effect transistor based methods are presented along with selected promising novel approaches, such as nanowire or magnetic nanoparticle-based biosensing. Addnl. measurement techniques, which have been shown useful in combination with electrochem. detection, are also summarized, such as the electrochem. versions of surface plasmon resonance, optical waveguide lightmode spectroscopy, ellipsometry, quartz crystal microbalance, and scanning probe microscopy. The signal transduction and the general performance of electrochem. sensors are often detd. by the surface architectures that connect the sensing element to the biol. sample at the nanometer scale. The most common surface modification techniques, the various electrochem. transduction mechanisms, and the choice of the recognition receptor mols. all influence the ultimate sensitivity of the sensor. New nanotechnol.-based approaches, such as the use of engineered ion-channels in lipid bilayers, the encapsulation of enzymes into vesicles, polymersomes, or polyelectrolyte capsules provide addnl. possibilities for signal amplification. In particular, this review highlights the importance of the precise control over the delicate interplay between surface nano-architectures, surface functionalization and the chosen sensor transducer principle, as well as the usefulness of complementary characterization tools to interpret and to optimize the sensor response.
- 18Kozma, P.; Kehl, F.; Ehrentreich-förster, E.; Stamm, C.; Bier, F. F. Integrated Planar Optical Waveguide Interferometer Biosensors: A Comparative Review. Biosens. Bioelectron. 2014, 58, 287– 307, DOI: 10.1016/j.bios.2014.02.04918https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXmsFGisLo%253D&md5=02729874ca8e0ff5065399ec57eff348Integrated planar optical waveguide interferometer biosensors: A comparative reviewKozma, Peter; Kehl, Florian; Ehrentreich-Foerster, Eva; Stamm, Christoph; Bier, Frank F.Biosensors & Bioelectronics (2014), 58 (), 287-307CODEN: BBIOE4; ISSN:0956-5663. (Elsevier B.V.)A review. Integrated planar optical waveguide interferometer biosensors are advantageous combinations of evanescent field sensing and optical phase difference measurement methods. By probing the near surface region of a sensor area with the evanescent field, any change of the refractive index of the probed vol. induces a phase shift of the guided mode compared to a ref. field typically of a mode propagating through the ref. arm of the same waveguide structure. The interfering fields of these modes produce an interference signal detected at the sensor's output, whose alteration is proportional to the refractive index change. This signal can be recorded, processed and related to e.g. the concn. of an analyte in the soln. of interest. Although this sensing principle is relatively simple, studies about integrated planar optical waveguide interferometer biosensors can mostly be found in the literature covering the past twenty years. During these two decades, several members of this sensor family have been introduced, which have remarkably advantageous properties. These entail label-free and non-destructive detection, outstandingly good sensitivity and detection limit, cost-effective and simple prodn., ability of multiplexing and miniaturization. Furthermore, these properties lead to low reagent consumption, short anal. time and open prospects for point-of-care applications. The present review collects the most relevant developments of the past twenty years categorizing them into two main groups, such as common- and double path waveguide interferometers. In addn., it tries to maintain the historical order as it is possible and it compares the diverse sensor designs in order to reveal not only the development of this field in time, but to contrast the advantages and disadvantages of the different approaches and sensor families, as well.
- 19Estevez, M. C.; Alvarez, M.; Lechuga, L. M. Integrated Optical Devices for Lab-on-a-Chip Biosensing Applications. Laser Photonics Rev. 2012, 6, 463– 487, DOI: 10.1002/lpor.201100025There is no corresponding record for this reference.
- 20Chalyan, T.; Guider, R.; Pasquardini, L.; Zanetti, M.; Falke, F.; Schreuder, E.; Heideman, R. G.; Pederzolli, C.; Pavesi, L. Asymmetric Mach-Zehnder Interferometer Based Biosensors for Aflatoxin M1 Detection. Biosensors 2016, 6, 1– 10, DOI: 10.3390/bios601000120https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXmtFemsrY%253D&md5=b189b049e0980be28ec5dbb06921c9e0Asymmetric Mach-Zehnder Interferometer based biosensors for Aflatoxin M1 detectionChalyan, Tatevik; Guider, Romain; Pasquardini, Laura; Zanetti, Manuela; Falke, Floris; Schreuder, Erik; Heideman, Rene G.; Pederzolli, Cecilia; Pavesi, LorenzoBiosensors (2016), 6 (1), 1/1-1/10CODEN: BIOSHU; ISSN:2079-6374. (MDPI AG)In this work, we present a study of Aflatoxin M1 detection by photonic biosensors based on Si3N4 Asym. Mach -Zehnder Interferometer (aMZI) functionalized with antibodies fragments (Fab'). We measured a best volumetric sensitivity of 104 rad/RIU, leading to a Limit of Detection below 5 10-7 RIU. On sensors functionalized with Fab', we performed specific and non-specific sensing measurements at various toxin concns. Reproducibility of the measurements and re-usability of the sensor were also investigated.
- 21Fernández-Gavela, A.; Herranz, S.; Chocarro, B.; Falke, F.; Schreuder, E.; Leeuwis, H.; Heideman, R. G.; Lechuga, L. M. Full Integration of Photonic Nanoimmunosensors in Portable Platforms for On-Line Monitoring of Ocean Pollutants. Sens. Actuators, B 2019, 297, 126758 DOI: 10.1016/j.snb.2019.12675821https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhtlKqtb3F&md5=f8d4757591f9fa2fe8467f1604c1d0f3Full integration of photonic nanoimmunosensors in portable platforms for on-line monitoring of ocean pollutantsFernandez-Gavela, Adrian; Herranz, Sonia; Chocarro, Blanca; Falke, Floris; Schreuder, Erik; Leeuwis, Henk; Heideman, Rene G.; Lechuga, Laura M.Sensors and Actuators, B: Chemical (2019), 297 (), 126758CODEN: SABCEB; ISSN:0925-4005. (Elsevier B.V.)A photonic nano-immunosensor platform for the on-site anal. of harmful org. ocean pollutants, intended to be allocated in stand-alone buoys was developed. The main aim was to bring the monitoring tools directly to the contaminated place, resulting in cost and time saving as compared to the std. anal. techniques. As sensor an integrated asym. Mach-Zehnder interferometer (aMZI) of micro/nano dimensions was employed, based on silicon photonic technol. In order to obtain a multiplexed system, a four-channel microfluidic cell was designed, manufd. and incorporated in the miniaturized sensor. Addnl., a microfluidic delivery module enabling automatic sample anal. was designed, evaluated and assembled. Moreover, the optical interconnections of the sensor chip was implemented by fiber optics, as well the electronics and the required software and data processing. Pollutant detection was based on a competitive immunoassay using bioreceptors previously biofunctionalized on the aMZI sensor arms and incubation with a specific antibody. As proof of concept, two types of pollutants were analyzed: the biocide Irgarol 1051, and the antibiotic Tetracycline. Results showed limits of detection in the range of few ng/mL, accomplished the European legislation.
- 22Heideman, R.; Hoekman, M.; Schreuder, E. TriPleX-Based Integrated Optical Ring Resonators for Lab-on-a-Chip and Environmental Detection. J. Sel. Top. Quantum Electron. 2012, 18, 1583– 1596, DOI: 10.1109/JSTQE.2012.218838222https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhsFyitLfO&md5=30ef97b79efbb78c814647e44f104c53TriPleX-based integrated optical ring resonators for lab-on-a-chip and environmental detectionHeideman, Rene; Hoekman, Marcel; Schreuder, ErikIEEE Journal of Selected Topics in Quantum Electronics (2012), 18 (5), 1583-1596CODEN: IJSQEN; ISSN:1077-260X. (Institute of Electrical and Electronics Engineers)In this paper, we report exptl. results of integrated optics ring resonators (RRs) based on TriPleX waveguide technol. The RRs operate in the near IR enabling the use of very cost effective VCSELs as a light source. The exptl. obtained response of the ring resonators is in good agreement with theory, while the measured through and drop responses show very low on-chip losses. The chips show good coupling efficiencies to external fibers due to integrated spotsize converters. The corresponding signal-to-noise ratio enables for measurements of changes in refractive index (RI) smaller than 1 × 10-6 RIU. The RRs are combined with an 850-nm vertical-cavity surface-emitting laser (VCSEL) as a light source and prototype electronic equipment for signal processing. Several applications are described here, such as RI measurements in fluidic channels, label-free biochem. surface reactions, and gas detection in ambient atm.
- 23Gavela, A. F.; García, D. G.; Ramirez, J. C.; Lechuga, L. M. Last Advances in Silicon-Based Optical Biosensors. Sensors 2016, 16, 285 DOI: 10.3390/s16030285There is no corresponding record for this reference.
- 24Bastos, A. R.; Vicente, C. M. S.; Oliveira-Silva, R.; Silva, N. J. O.; Tacão, M.; da Costa, J. P.; Lima, M.; André, P. S.; Ferreira, R. A. S. Integrated Optical Mach-Zehnder Interferometer Based on Organic-Inorganic Hybrids for Photonics-on-a-Chip Biosensing Applications. Sensors 2018, 18, 840 DOI: 10.3390/s1803084024https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXisVWgurzI&md5=a2eba6f052e346e25a93a13741dfdb7dIntegrated optical mach-zehnder interferometer based on organic-inorganic hybrids for photonics-on-a-chip biosensing applicationsBastos, Ana R.; Vicente, Carlos M. S.; Oliveira-Silva, Rui; Silva, Nuno J. O.; Tacao, Marta; da Costa, Joao P.; Lima, Mario; Andre, Paulo S.; Ferreira, Rute A. S.Sensors (2018), 18 (3), 840/1-840/11CODEN: SENSC9; ISSN:1424-8220. (MDPI AG)The development of portable low-cost integrated optics-based biosensors for photonics-on-a-chip devices for real-time diagnosis are of great interest, offering significant advantages over current anal. methods. We report the fabrication and characterization of an optical sensor based on a Mach-Zehnder interferometer to monitor the growing concn. of bacteria in a liq. medium. The device pattern was imprinted on transparent self-patternable org.-inorg. di-ureasil hybrid films by direct UV-laser, reducing the complexity and cost prodn. compared with lithog. techniques or three-dimensional (3D) patterning using femtosecond lasers. The sensor performance was evaluated using, as an illustrative example, E. coli cell growth in an aq. medium. The measured sensitivity (2 × 10-4 RIU) and limit of detection (LOD = 2 × 10-4) are among the best values known for low-refractive index contrast sensors. Furthermore, the di-ureasil hybrid used to produce this biosensor has addnl. advantages, such as mech. flexibility, thermal stability, and low insertion losses due to fiber-device refractive index mismatch (∼1.49). Therefore, the proposed sensor constitutes a direct, compact, fast, and cost-effective soln. for monitoring the concn. of lived-cells.
- 25Liu, Q.; Tu, X.; Woo, K.; Sheng, J.; Shin, Y.; Han, K.; Yoon, Y.; Lo, G.; Kyoung, M. Highly Sensitive Mach–Zehnder Interferometer Biosensor Based on Silicon Nitride Slot Waveguide. Sens. Actuators, B 2013, 188, 681– 688, DOI: 10.1016/j.snb.2013.07.05325https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhs1SgurfF&md5=de687567c1d18c24e9aaa13afea147f0Highly sensitive Mach-Zehnder interferometer biosensor based on silicon nitride slot waveguideLiu, Qing; Tu, Xiaoguang; Kim, Kyung Woo; Kee, Jack Sheng; Shin, Yong; Han, Kyungsup; Yoon, Yong-Jin; Lo, Guo-Qiang; Park, Mi KyoungSensors and Actuators, B: Chemical (2013), 188 (), 681-688CODEN: SABCEB; ISSN:0925-4005. (Elsevier B.V.)We demonstrate a highly sensitive label-free Mach-Zehnder interferometer (MZI) biosensor based on silicon nitride slot waveguide. Unlike the conventional MZI sensors, the sensing arm of the sensor consists of a slot waveguide while the ref. arm consists of a strip waveguide. Thanks to the slot waveguide's property to provide high optical intensity in a subwavelength-size low refractive index region (slot region), which allows high light-analyte interaction, higher sensitivity can be obtained as compared to conventional waveguides using the slot waveguide as sensing region. The bulk refractive index sensitivity of the slot waveguide MZI sensor was found to be 1864π/RIU (refractive index unit) with 7 mm long slot waveguide sensing arm, which shows higher sensitivity compared to the conventional MZI device based on silicon nitride. The biosensing capability of the developed slot waveguide MZI was investigated using biotin-streptavidin binding as a model system. The sensitivity of the system was demonstrated down to 18.9 fM or 1 pg/mL of streptavidin soln. and to the best of our knowledge, it is the best reported exptl. value for the limit of detection of a MZI sensor. Furthermore, we investigated the specific detection and quantification of the methylation of DAPK (Death-assocd. protein kinase) gene, which is a widely used biomarker for human cancers. We have shown that methylation sequences of DAPK gene of various methylation densities (100%, 50%, and 0% of methylation sites) can be quantified and discriminated even at a concn. as low as 1 fmol/μl or 1 nM.
- 26Psarouli, A.; Botsialas, A.; Salapatas, A.; Stefanitsis, G.; Nikita, D.; Jobst, G.; Chaniotakis, N.; Goustouridis, D.; Makarona, E.; Petrou, P. S. Fast Label-Free Detection of C-Reactive Protein Using Broad-Band Mach-Zehnder Interferometers Integrated on Silicon Chips. Talanta 2017, 165, 458– 465, DOI: 10.1016/j.talanta.2017.01.00126https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXntlehsg%253D%253D&md5=b8c20b6703144dc34152cc7d9eb93833Fast label-free detection of C-reactive protein using broad-band Mach-Zehnder interferometers integrated on silicon chipsPsarouli, Aimilia; Botsialas, Athanasios; Salapatas, Alexandros; Stefanitsis, Gerasimos; Nikita, Dimitra; Jobst, Gerhard; Chaniotakis, Nikolaos; Goustouridis, Dimitrios; Makarona, Eleni; Petrou, Panagiota S.; Raptis, Ioannis; Misiakos, Konstantinos; Kakabakos, Sotirios E.Talanta (2017), 165 (), 458-465CODEN: TLNTA2; ISSN:0039-9140. (Elsevier B.V.)An immunosensor for fast and accurate detn. of C-reactive protein (CRP) in human serum samples based on an array of all-silicon broad-band Mach-Zehnder interferometers (BB-MZIs) is demonstrated. The detection was based on monitoring the spectral shifts during the binding of CRP on the antibody mols. that have been immobilized on the sensing arms of the BB-MZIs. By employing the reaction rate as the anal. signal the assay time was compressed to few minutes. The detection limit was 2.1 ng/mL, the quantification limit was 4.2 ng/mL and the linear dynamic range extended up to 100 ng/mL. The measurements performed in human serum samples with the developed immunosensor were characterized by high repeatability and accuracy as it was demonstrated by diln. linearity and recovery expts. In addn., the concn. values detd. were in excellent agreement with those detd. for the same samples by a std. clin. lab. method. The compact size of the chip makes the proposed immunosensor attractive for incorporation into miniaturized devices for the detn. of clin. analytes at the point-of-need.
- 27Gauglitz, G.; Ingenhoff, J. Design of New Integrated Optical Substrates for Immuno-Analytical Applications. Fresenius’ J. Anal. Chem. 1994, 349, 355– 359, DOI: 10.1007/BF0032659927https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2cXlt12js70%253D&md5=23e81913db0fa08f97cf43944825b0ceDesign of new integrated optical substrates for immuno-analytical applicationsGauglitz, G.; Ingenhoff, J.Fresenius' Journal of Analytical Chemistry (1994), 349 (5), 355-9CODEN: FJACES; ISSN:0937-0633.Integrated optical Mach-Zehnder interferometers supply information on changes in refractive index and/or thickness of a film placed as a superstrate on top of one of its surface wave-guides. The internal propagation of light is influenced by the evanescent field reaching into the superstrate. This propagating light interferes with an uninfluenced wave in the second arm after recombination. The result is an intensity modulation depending on the refractive index parameters of the substrate, the waveguide itself and the properties of the superstrate. Taking an antigen layer as the superstrate, its interaction with antibodies changes its thickness by several nanometers. This can be obsd. by recording the change in intensity of the signal of the interferometer. The sensitivity of such a device depends on particular values of the optical parameters of substrate and waveguide with respect to the given superstrate properties. Computer calcns. help to select optimum glass and waveguide fabrication conditions. The numerical results of a variety of assumed conditions have been tested exptl. The application to the improved detection of triazines is discussed.
- 28Brosinger, F.; Freimuth, H.; Lacher, M.; Ehrfeld, W.; Gedig, E.; Katerkamp, A.; Spener, F.; Cammann, K. A Label-Free Affinity Sensor with Compensation of Unspecific Protein Interaction by a Highly Sensitive Integrated Optical Mach-Zehnder Interferometer on Silicon. Sens. Actuators, B 1997, 44, 350– 355, DOI: 10.1016/S0925-4005(97)00226-828https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK1cXosFGnug%253D%253D&md5=18eabe5f89fc387ac72dc09869cb3c5fA label-free affinity sensor with compensation of unspecific protein interaction by a highly sensitive integrated optical Mach-Zehnder interferometer on siliconBrosinger, Franz; Freimuth, Herbert; Lacher, Manfred; Ehrfield, Wolfgang; Gedig, Erk; Katerkamp, Andreas; Spener, Friedrich; Cammann, KarlSensors and Actuators, B: Chemical (1997), 44 (1-3), 350-355CODEN: SABCEB; ISSN:0925-4005. (Elsevier Science S.A.)An integrated optical Mach-Zehnder interferometer (IO-MZI) on silicon was specially designed and tested for application as an affinity sensor. In order to obtain the necessary sensitivity, an optimization of the refractive index and the thickness of the wave-guiding layer was carried out. Refractive measurements with ethanol/water mixts. show a sensitivity of about one order of magnitude higher than the IO-MZIs previously described. The compensation of unspecific protein interaction in an affinity sensor set-up was demonstrated by using both branches of the IO-MZI. One branch was coated with a antigenic structure and sensor set-up was demonstrated by using both branches of the IO-MZI. One branch was coated with a antigenic structure and blocked with a protein mixt. whereas the other was only blocked. A sample with a high background of serum proteins was applied and only the sample contg. the specific antibody gave a measurable signal.
- 29Song, B.; Zhang, H.; Liu, B.; Lin, W.; Wu, J. Label-Free in-Situ Real-Time DNA Hybridization Kinetics Detection Employing Microfiber-Assisted Mach-Zehnder Interferometer. Biosens. Bioelectron. 2016, 81, 151– 158, DOI: 10.1016/j.bios.2016.02.06529https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XjsFKgu7c%253D&md5=f57f16586bae648c2bc1855c8e080cbdLabel-free in-situ real-time DNA hybridization kinetics detection employing microfiber-assisted mach-Zehnder interferometerSong, Binbin; Zhang, Hao; Liu, Bo; Lin, Wei; Wu, JixuanBiosensors & Bioelectronics (2016), 81 (), 151-158CODEN: BBIOE4; ISSN:0956-5663. (Elsevier B.V.)A label-free DNA biosensor based on microfiber-assisted Mach-Zehnder interferometer (MAMZI) for in-situ real-time DNA hybridization kinetics detection has been proposed and exptl. demonstrated. A microfiber of hundreds of microns in length is fabricated by tapering a segment of std. single-mode fiber (SMF) to construct the U-shaped microcavity between the lead-in and lead-out SMFs. Thanks to the mode field mismatching between the SMF and microfiber, the incident guided mode light would sep. into two beams that resp. propagate in the air microcavity and the microfiber. Consequently, interference between different light modes would occur at the joint between the microfiber and the lead-out SMF. Exptl. results indicate that owing to the participation of opening cavity modes in the modal interference process, the interferometric spectrum of our proposed microcavity sensor is highly sensitive to the variation of environmental refractive index (RI), esp. for the RI range around 1.34 which is useful for most biol. applications. The microfiber functionalization is achieved by stepwise modifying the microfiber with monolayer Poly-L-lysine (PLL) and single-stranded DNA (ssDNA) probes to produce the sensitive surface that could uniquely attach specific target ssDNAs. The fiber surface functionalization as well as DNA hybridization processes have been exptl. investigated for different target ssDNA solns. in real time. The interferometric transmission spectrum shows large wavelength shift for different biol. phases, and a detection limit conservatively down to 0.0001 pmol/μL has been acquired by employing the U-shaped microcavity of 176.88 μm in length. Our proposed DNA biosensor possesses several advantages such as compact size, ease of fabrication, and strong response for DNA hybridization, which make it a promising candidate for potential applications in such rapidly expanding areas as medical diagnosis, cancer screenings, medicine examn. and environmental engineering, etc.
- 30Movilli, J.; Rozzi, A.; Ricciardi, R.; Corradini, R.; Huskens, J. Control of Probe Density at DNA Biosensor Surfaces Using Poly-l-Lysine with Appended Reactive Groups. Bioconjugate Chem. 2018, 29, 4110– 4118, DOI: 10.1021/acs.bioconjchem.8b0073330https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXitFeku7%252FP&md5=5b63b9dd577f904a65d9542c11b4aa6dControl of Probe Density at DNA Biosensor Surfaces Using Poly(L-lysine) with Appended Reactive GroupsMovilli, Jacopo; Rozzi, Andrea; Ricciardi, Roberto; Corradini, Roberto; Huskens, JurriaanBioconjugate Chemistry (2018), 29 (12), 4110-4118CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)Biosensors and materials for biomedical applications generally require chem. functionalization to bestow their surfaces with desired properties, such as specific mol. recognition and antifouling properties. The use of modified poly(L-lysine) (PLL) polymers with appended oligo(ethylene glycol) (OEG) and thiol-reactive maleimide (Mal) moieties (PLL-OEG-Mal) offers control over the presentation of functional groups. These reactive groups can readily be conjugated to, for example, probes for DNA detection. Here we demonstrate the reliable conjugation of thiol-functionalized peptide nucleic acid (PNA) probes onto predeposited layers of PLL-OEG-Mal and the control over their surface d. in the preceding synthetic step of the PLL modification with Mal groups. By monitoring the quartz crystal microbalance (QCM) frequency shifts of the binding of complementary DNA vs. the d. of Mal moieties grafted to the PLL, a linear relationship between probe d. and PLL grafting d. was found. Cyclic voltammetry expts. using Methylene Blue-functionalized DNA were performed to establish the abs. probe d. values at the biosensor surfaces. These data provided a d. of 1.2 × 1012 probes per cm2 per % of grafted Mal, thus confirming the validity of the d. control in the synthetic PLL modification step without the need of further surface characterization.
- 31Di Iorio, D.; Marti, A.; Koeman, S.; Huskens, J. Clickable Poly-l-Lysine for the Formation of Biorecognition Surfaces. RSC Adv. 2019, 9, 35608– 35613, DOI: 10.1039/C9RA08714A31https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXitVygsb%252FM&md5=cab61dc322381a730fc643d237519527Clickable poly-L-lysine for the formation of biorecognition surfacesDi Iorio, Daniele; Marti, Almudena; Koeman, Sander; Huskens, JurriaanRSC Advances (2019), 9 (61), 35608-35613CODEN: RSCACL; ISSN:2046-2069. (Royal Society of Chemistry)Biomols. are immobilized onto surfaces employing the fast and stable adsorption of poly-L-lysine (PLL) polymers and the versatile copper-free click chem. reactions. This method provides the combined advantages of versatile surface adsorption with d. control using polyelectrolytes and of the covalent and orthogonal immobilization of biomols. with higher reaction rates and improved yields of click chem. Using DNA attachment as a proof of concept, control over the DNA probe d. and applicability in electrochem. detection are presented.
- 32Sauerbrey, G. Verwendung von Schwingquarzen Zur Wägung Dünner Schichten Und Zur Mikrowägung. Z. Phys. 1959, 155, 206– 222, DOI: 10.1007/BF0133793732https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaG1MXoslSjtQ%253D%253D&md5=ff97a9cc63637eb9823aebfeb57a367bThe use of quartz oscillators for weighing thin layers and for microweighingSauerbrey, GuntherZeitschrift fuer Physik (1959), 155 (), 206-22CODEN: ZEPYAA; ISSN:0044-3328.The frequency of a quartz plate is altered if a layer of foreign material is deposited on the quartz, e.g. by evapn. Since changes in frequency can be measured very accurately, the phenomenon can be used for weighing thin layers. The change in frequency is proportional to the d. of the foreign layer and the proportionality const. can be calcd. from the characteristic frequency of the quartz plate. The accuracy of the method is limited by the temp. variation of the characteristic frequency of the quartz oscillator. For a temp. fluctuation of 1° the accuracy is ±4.10-9 g./cm. This corresponds to a mean thickness of the layer of 0.4 A. at a d. of 1 g./cc. The method can also be used for direct microweighing, e.g. by evapg. a drop of a soln. on the quartz plate.
- 33Larsson, C.; Rodahl, M.; Höök, F. Characterization of DNA Immobilization and Subsequent Hybridization on a 2D Arrangement of Streptavidin on a Biotin-Modified Lipid Bilayer Supported on SiO2. Anal. Chem. 2003, 75, 5080– 5087, DOI: 10.1021/ac034269n33https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXms1aqsbY%253D&md5=90361694a37d1e2314cab0865ef2c656Characterization of DNA immobilization and subsequent hybridization on a 2D arrangement of streptavidin on a biotin-modified lipid bilayer supported on SiO2Larsson, Charlotte; Rodahl, Michael; Hoeoek, FredrikAnalytical Chemistry (2003), 75 (19), 5080-5087CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)We show how the water content (and effective d.) of thin adsorbed films composed of biomols. can be detd. using combined quartz crystal microbalance with dissipation monitoring (QCM-D) and surface plasmon resonance (SPR) anal. In particular, these techniques, combined with theor. treatment using a Voigt-based viscoelastic model, were applied to analyze the state of surface immobilized single stranded biotin-modified probe DNA (b-DNA) coupled via streptavidin to a biotin-doped supported phospholipid bilayer (b-SPB). From a proper anal., it is demonstrated how changes in effective thickness, δf, and the viscoelastic components (shear viscosity, ηf, and shear elasticity, μf) can be obtained during both DNA immobilization and hybridization with single stranded fully complementary target DNA. In particular, it is demonstrated how this type of anal. can be used to control the state of streptavidin arrangement for improved measurements of DNA hybridization kinetics. The latter is demonstrated by identifying a surface-coverage dependent viscoelastic behavior of immobilized b-DNA, which is shown to influence the hybridization efficiency.
- 34Seifert, M.; Rinke, M. T.; Galla, H. J. Characterization of Streptavidin Binding to Biotinylated, Binary Self-Assembled Thiol Monolayers - Influence of Component Ratio and Solvent.. Langmuir 2010, 26, 6386– 6393, DOI: 10.1021/la904087s34https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhvFKhsr8%253D&md5=a9ba964b7d4170d369a90b060632efa9Characterization of Streptavidin Binding to Biotinylated, Binary Self-Assembled Thiol Monolayers - Influence of Component Ratio and SolventSeifert, Michael; Rinke, Matthias T.; Galla, Hans-JoachimLangmuir (2010), 26 (9), 6386-6393CODEN: LANGD5; ISSN:0743-7463. (American Chemical Society)Many biosensor applications are based on streptavidin (SA) binding to partially biotinylated self-assembled thiol monolayers (SAMs). In the authors' study, binary SAMs on gold were prepd. from solns. contg. 16-mercapto-1-hexadecanol (thiol I) and N-(8-biotinyl-3,6-dioxa-octanamidyl)-16-mercaptohexadecanamide (thiol II) in varying component ratios. Either chloroform or ethanol was used as solvent. After 24 h thiol incubation, SA was immobilized on the resulting SAMs using the strong SA-biotin interaction. The SA binding process was monitored by QCM-D (quartz crystal microbalance monitoring dissipation factor). It is shown that the Sauerbrey equation is valid to calc. the mass quantities of the immobilized SA layers. Under the chosen incubation conditions, marginal fractions of the biotinylated component II in chloroform ((nI/nII)solution ≈ 1000) lead to SAMs which ensure a maximal SA binding quantity of mSauerbrey SA ≈ 400 ng/cm-2, being equiv. to a SA single-layer arrangement on the SAM surface. In case of incubations from ethanolic solns., a complete SA layer formation needs significantly higher amts. of the biotinylated component II during SAM prepn. ((nI/nII)solution ≈ 50). XPS data show that the fraction of biotinylated thiol II in the SAM dets. the amt. of surface-bound SA. The SAM thiol ratio ((nI/nII)SAM) not only depends on the corresponding component ratio in the incubation soln., but is also strongly influenced by the solvent. Using chloroform as solvent during SAM prepn. significantly increased the fraction of biotinylated thiol II in the SAMs compared to ethanol.
- 35Vogt, B. D.; Soles, C. L.; Lee, H. J.; Lin, E. K.; Wu, W. L. Moisture Absorption and Absorption Kinetics in Polyelectrolyte Films: Influence of Film Thickness. Langmuir 2004, 20, 1453– 1458, DOI: 10.1021/la035239i35https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXjslaiug%253D%253D&md5=4f1ba3c81a9df7467efd40b749ddd64eMoisture Absorption and Absorption Kinetics in Polyelectrolyte Films: Influence of Film ThicknessVogt, Bryan D.; Soles, Christopher L.; Lee, Hae-Jeong; Lin, Eric K.; Wu, Wen-liLangmuir (2004), 20 (4), 1453-1458CODEN: LANGD5; ISSN:0743-7463. (American Chemical Society)Specular X-ray reflectivity (XR) and quartz crystal microbalance (QCM) measurements were used to det. the absorption of water into thin poly(ammonium 4-styrenesulfonic acid) films from satd. vapor at 25 °C. The effect of film thickness on the absorption kinetics and overall absorption was investigated in the range of thickness from (3 to 200) nm. The equil. swelling of all the films irresp. of film thickness was (0.57 ± 0.03) vol. fraction. Although the equil. absorption is independent of thickness, the absorption rate substantially decreases for film thickness < 100 nm. For the thinnest film (3 nm), there is a 5 orders of magnitude decrease in the diffusion coeff. for water.
- 36Besselink, G. A. J.; Heideman, R. G.; Schreuder, E.; Wevers, L. S.; Falke, F.; van den Vlekkert, H. H. Performance of Arrayed Microring Resonator Sensors with the TriPleX Platform. J. Biosens. Bioelectron. 2016, 7, 1000209 DOI: 10.4172/2155-6210.1000209There is no corresponding record for this reference.
- 37Duan, X.; Mu, L.; Sawtelle, S. D.; Rajan, N. K.; Han, Z.; Wang, Y.; Qu, H.; Reed, M. A. Functionalized Polyelectrolytes Assembling on Nano-BioFETs for Biosensing Applications. Adv. Funct. Mater. 2015, 25, 2279– 2286, DOI: 10.1002/adfm.20150000237https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXkvF2gtb0%253D&md5=3b2c1c95f9423fecb79aba5632a93092Functionalized Polyelectrolytes Assembling on Nano-BioFETs for Biosensing ApplicationsDuan, Xuexin; Mu, Luye; Sawtelle, Sonya D.; Rajan, Nitin K.; Han, Ziyu; Wang, Yanyan; Qu, Hemi; Reed, Mark A.Advanced Functional Materials (2015), 25 (15), 2279-2286CODEN: AFMDC6; ISSN:1616-301X. (Wiley-VCH Verlag GmbH & Co. KGaA)A new surface functionalization scheme for nano-Bio field effect transistors (FETs) using biocompatible polyelectrolyte thin films (PET) is developed. PET assemblies on Si nanowires (Si-NWs) are driven by electrostatic interactions between the pos. charged polymer backbone and neg. charged Si/SiO2 surface. Such assemblies can be directly coated from PET aq. solns. and result in a uniform nanoscale thin film, which is more stable compared to the conventional amine silanization. Short oligo-ethylene glycol chains are grafted on the PETs to prevent nonspecific protein binding. Moreover, the reactive groups of the polymer chains can be further functionalized to other chem. groups in specific stoichiometry for biomols. detection. Therefore, it opens a new strategy to precisely control the functional group densities on various biosensor surfaces at the mol. level. In addn., such assemblies of the polymers together with the bound analytes can be removed with the pH stimulation resulting in regeneration of a bare sensor surface without compromising the integrity and performance of the Si-NWs. Thus, it is believed that the developed PET coating and sensing systems on Si-NW FETs represent a versatile, promising approach for regenerative biosensors which can be applied to other biosensors and will benefit real device applications, enhancing sensor lifetime, reliability, and repeatability.