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Competitive Upconversion-Linked Immunosorbent Assay for the Sensitive Detection of Diclofenac

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† Institute of Analytical Chemistry, Chemo- and Biosensors, University of Regensburg, 93040 Regensburg, Germany
‡ CEITEC−Central European Institute of Technology, Masaryk University, Brno 625 00, Czech Republic
§ Institute of Analytical Chemistry AS CR, v. v. i., Brno 602 00, Czech Republic
∥ Chair of Analytical Chemistry and Institute of Hydrochemistry, Technical University of Munich, 81377 Munich, Germany
*Phone: +49-941-943-4015. Fax: +49-941-943-4064. E-mail: [email protected]
Cite this: Anal. Chem. 2016, 88, 11, 6011–6017
Publication Date (Web):May 11, 2016
https://doi.org/10.1021/acs.analchem.6b01083

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Abstract

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Photon-upconverting nanoparticles (UCNPs) emit light of shorter wavelength under near-infrared excitation and thus avoid optical background interference. We have exploited this unique photophysical feature to establish a sensitive competitive immunoassay for the detection of the pharmaceutical micropollutant diclofenac (DCF) in water. The so-called upconversion-linked immunosorbent assay (ULISA) was critically dependent on the design of the upconversion luminescent detection label. Silica-coated UCNPs (50 nm in diameter) exposing carboxyl groups on the surface were conjugated to a secondary anti-IgG antibody. We investigated the structure and monodispersity of the nanoconjugates in detail. Using a highly affine anti-DCF primary antibody, the optimized ULISA reached a detection limit of 0.05 ng DCF per mL. This performance came close to a conventional enzyme-linked immunosorbent assay (ELISA) without the need for an enzyme-mediated signal amplification step. The ULISA was further employed for analyzing drinking and surface water samples. The results were consistent with a conventional ELISA as well as liquid chromatography–mass spectrometry (LC–MS).

The enzyme-linked immunosorbent assay (ELISA) is a cost efficient tool for the specific and highly sensitive detection of many toxic analytes in food and environmental samples as well as clinical diagnosis. There are, however, some disadvantages of a classic ELISA such as an inherent instability of enzymes and time-consuming signal development. Consequently, many research efforts have been made to replace the enzymes by using nanoparticles (NPs) as signal amplifiers, e.g., fluorescent dye-doped polymer or silica NPs, (1) metal NPs, (2) magnetic NPs, (3) catalytic NPs, (4) or quantum dots. (5) Recently, photon-upconverting nanoparticles (UCNPs) have been used as a new generation of luminescent labels for sensitive immunochemical detection. UCNPs are lanthanide-doped nanocrystals that can be excited by near-infrared light and emit light of shorter wavelengths (anti-Stokes emission), (6, 7) which strongly reduces autofluorescence and light scattering. Further advantages of UCNPs include (A) a very high photostability, (B) large anti-Stokes shifts allowing for an excellent separation of excitation and detection channels, and (C) multiple and narrow emission bands that can be tuned individually for the multiplexed detection of analytes. (8-10)
These distinct photophysical features of UCNPs have been used for the design of heterogeneous microtiter plate immunoassays, e.g., for the detection of prostate-specific antigen (limit of detection, LOD, 0.15 ng mL–1/6 pM) (11) or human chorionic gonadotropin (LOD, 3.8 ng mL–1/200 pM). (12) The advantages of UCNPs in lateral flow assays, e.g., for the detection of worm parasite antigens (LOD, 0.01 ng mL–1/0.1 pM) (13) have also been well documented. There have been a few reports on the use of homogeneous competitive immunoassays for the detection of small molecules such as estradiol (LOD, ∼0.1 ng mL–1/400 pM) (14) and folate (LOD, 0.4 ng mL–1/1000 pM) (15) in blood and a bead-based immunoassay for the detection of mycotoxins in food samples (LOD, ∼0.01 ng mL–1/50 pM). (16)
The development and widespread availability of more sensitive analytical techniques has resulted in an increasing number of pharmaceuticals that can be detected in the environment after medical or veterinary use. (17, 18) Diclofenac (2-[2-(2,6-dichlorophenyl) aminophenyl] ethanoic acid; DCF) is a widely used nonsteroidal anti-inflammatory drug (NSAID). In the Indian subcontinent, the widespread use of DCF for veterinary treatment of cattle since the 1990s has led to a precipitous decline of the indigenous vulture population because DCF leads to renal failure in vultures that feed on contaminated carcasses. (19) In Europe, DCF belongs to the most frequently detected pharmaceuticals in the water-cycle because it is not easily degraded when passing through sewage treatment plants. DCF has been detected in low μg L–1 amounts in wastewater effluents and also in ng L–1 amounts in surface waters, (20) groundwater, and drinking water. (21) Very low amounts of DCF can be detected by liquid chromatography–time-of-flight-mass spectrometry (LC–TOF-MS) or high-resolution mass spectrometers. (22, 23) These instrumental techniques, however, are expensive, time-consuming, labor intensive and need trained personnel. By contrast, immunoassays are more suitable for on-site testing directly in the field or for the analysis of large numbers of samples in small laboratories. (24)
Here, we have optimized the preparation of monodisperse and stable upconversion reporters for the sensitive detection of DCF in water samples by a competitive upconversion-linked immunosorbent assay (ULISA). Anti-mouse IgG antibodies were conjugated to silica-coated UCNPs exposing carboxyl function on the surface and the conjugates were characterized by gel electrophoresis. (25) The competitive detection of DCF was performed using a monoclonal mouse anti-DCF antibody (Figure 1). This antibody was characterized in detail as described recently (26) and showed about 10% cross-reactivity with DCF metabolites such as 5-OH-DCF, 4′-OH-DCF, and DCF-acyl glucuronide but only less than 1% with other structurally related nonsteroidal anti-inflammatory drugs. The performance of the optimized ULISA was compared with a conventional ELISA as well as LC–MS.

Figure 1

Figure 1. Scheme of the indirect competitive ULISA for the detection of diclofenac (DCF). (A) A microtiter plate is coated with a bovine serum albumin-DCF conjugate (BSA-DCF). (B) Dilution series of DCF are prepared in the microtiter plate followed by the addition of anti-DCF mouse antibody. (C) The attachment of anti-DCF antibody is then detected by an anti-mouse IgG-UCNP secondary antibody conjugate. The upconversion luminescence is recorded under 980 nm laser excitation.

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Experimental Section

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Chemicals

All standard chemicals and diclofenac sodium salt (D6899, purity ≥98%) were obtained from Sigma-Aldrich (Steinheim, Germany). Carboxyethylsilanetriol sodium salt; 25% (w/v) in water was obtained from ABCR GmbH (Karlsruhe, Germany). The horseradish peroxidase-labeled horse anti-mouse IgG was from Axxora (Lörrach, Germany) and horse anti-mouse IgG was from Vector Laboratories (Burlingame). The monoclonal anti-diclofenac antibody 12G5 was generated in mice using a DCF-thyroglobulin conjugate as described previously. (26) An antibody stock solution of 0.45 mg mL–1 was prepared in 20 mM NaH2PO4, 0.1 M Tris-HCl, 0.02% NaN3, pH 7.4 and stored at 4 °C. Buffers and solutions were prepared with ultrapure water, which was obtained by reverse osmosis with UV treatment (Milli-RO 5 Plus, Milli-Q185 Plus, Eschborn, Germany).

Synthesis of Carboxyl-Silica-Coated UCNPs

UCNPs of 42.5 ± 4.9 nm in diameter were synthesized by high-temperature coprecipitation (27) as described in the Supporting Information. The mass concentration was determined by gravimetric analysis and a concentration of 1.0 mg mL–1 of UCNPs was estimated to be equivalent to the molar concentration of 9.8 × 10–9 mol L–1 (Supporting Information).
Carboxyl-silica-coated UCNPs (COOH-UCNPs) were prepared by a reverse microemulsion method: (25) UCNPs (80 mg) were diluted in cyclohexane to a final volume of 23 mL. This dispersion was mixed with 1800 mg of Igepal CO-520 and 100 μL of tetraethyl orthosilicate (TEOS) and stirred intensively for 10 min. A mixture of 55 μL 25% (w/v) of aqueous ammonium hydroxide and 55 μL of water was added to form a microemulsion that was slowly stirred overnight. Then, 25 μL of TEOS were added and the microemulsion was again stirred for 180 min. After adding 50 μL of 25% (w/v) sodium carboxyethylsilanetriol in water, the microemulsion was first sonicated for 15 min and then stirred for 60 min. The COOH-UCNPs were extracted with 1000 μL of dimethylformamide and washed four times with 20 mL of propan-2-ol, three times with 5000 μL of water and finally dispersed in water to yield a final concentration of 150 mg mL–1. The COOH-UCNPs in water were stable at 4 °C for several months.

Conjugation of COOH-UCNP and Secondary Antibody

COOH-UCNPs were first activated by 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide (EDC) and N-hydroxysulfosuccinimide (sulfo-NHS). In a typical synthesis, 0.5 mg (∼5 pmol) of COOH-UCNPs was dispersed in water to a final volume of 200 μL. The volume of 50 μL of a mixture containing 2.1 μmol of EDC and 5.5 μmol of sulfo-NHS in 100 μL of 100 mM sodium 2-(N-morpholino)ethanesulfonate (MES) buffer, pH 6.1 was added and mixed for 30 min. A dispersion of 100 μL of activated COOH-UCNPs (1 mg mL–1 or ∼10 nmol L–1) were mixed with 100 μL of horse anti-mouse IgG in borate buffer (100 mM sodium borate, pH 9.0). Three IgG concentrations were employed and incubated for 90 min at room temperature: (1) 330 nmol L–1 IgG resulting in a ratio 33 IgG molecules per UCNP (sample IgG-UCNP-33:1), (2) 67 nmol L–1 IgG resulting in a ratio of 7 IgG molecules per UCNP (IgG-UCNP-7:1), and (3) 33 nmol L–1 IgG resulting in a ratio of 3 IgG molecules per UCNP (IgG-UCNP-3:1). The bioconjugates were centrifuged for 10 min at 4 000g, dispersed in UCNP assay buffer (50 mM Tris, 150 mM NaCl, 0.05% NaN3, 0.01% Tween 20, 0.05% bovine γ-globulin (BGG), 0.5% bovine serum albumin (BSA), 0.2% poly(vinyl alcohol) 6000 (PVA), pH 7.75) and sonicated for 5 min.

Nanoparticle Characterization

Transmission electron microscopy (TEM) was performed on a Tecnai F20 FEI instrument (Eindhoven, The Netherlands). About 4 μL of UCNPs were deposited on a 400-mesh copper EM grid coated with a continuous carbon layer and negatively stained with 2% (w/v) aqueous solution of uranyl acetate to increase the contrast of the silica shell. The dried grids were then imaged at 50 000× magnification (2.21 Å pixel–1). The size of individual particles in the TEM images was measured by the imaging software ImageJ (http://imagej.nih.gov). (28) The hydrodynamic diameter and zeta potential of UCNP suspensions were determined on a Zetasizer Nano SZ from Malvern Instruments (Malvern, U.K.). FT-IR spectra were recorded on an Alpha FT-IR spectrometer from Bruker (Billerica, MA).

Agarose Gel Electrophoresis

Following our previous work, (25) COOH-UCNPs and their bioconjugates were characterized by agarose gel electrophoresis (0.5% w/v agarose, 45 mM Tris, 45 mM H3BO3 with pH 8.6, 15 min at 100 V). Samples were mixed in a ratio of 10:1 with 50% w/w glycerol and 8 μL aliquots were loaded onto the gel. A custom-built upconversion reader (Chameleon multilabel microplate reader, Hidex, Turku, Finland) equipped with a continuous 980 nm laser (4 W) was used to scan agarose gels with a spatial resolution of 0.5 mm as described earlier. (29)

Conjugation of Diclofenac to BSA

BSA-DCF conjugates were prepared using either 1.5 μmol or 7.5 μmol of DCF and 9.7 μmol of sulfo-NHS added to a mixture of 400 μL of MES buffer and 100 μL of dimethylformamide. DCF was activated by the addition of 47 μmol of EDC and incubation at room temperature for 30 min. After adding 500 μL of 0.15 μmol BSA in water and 250 μL of 50 mM aqueous Na2CO3, the mixture was incubated at room temperature for 4 h and then dialyzed (cellulose membrane, MWcut-off: 14 kDa, D9277, Sigma-Aldrich) three times against 150 mL of 50 mM Na2CO3. BSA-DCF was adjusted to a concentration of 1.6 mg mL–1 by adding 50 mM of Na2CO3 and stored at 4 °C in the presence of 0.05% NaN3. The conjugate was analyzed by matrix-assisted laser desorption ionization (MALDI)-TOF-MS (Bruker, Ultraflex TOF/TOF, N2-laser, 337 nm, positive mode).

Water Samples

Munich tap water and two surface water samples were collected in Southern Bavaria from Lake Wörthsee and the Würm River. The fresh water samples were filtrated over a glass microfiber filter (GF/C, Whatman catalog no. 1822 047) and stored at 4 °C. The concentrations of Ca2+, Mg2+, and total organic content (TOC) as well as the conductivity and pH were determined (Supporting Information, Table S1). ELISA and ULISA were performed with undiluted and spiked samples. For LC–MS, the samples were subjected to generic solid phase extraction (SPE) and analyzed by an Orbitrap-based Exactive benchtop mass spectrometer (Thermo Scientific, Dreieich, Germany) as described earlier. (26)

Upconversion-Linked Immunosorbent Assay

A transparent 96-well microtiter plate with high protein binding capacity (Corning, Wiesbaden, Germany) was coated with BSA-DCF in coating buffer (optimal concentration, 1 μg mL–1 BSA-DCF in 50 mM NaHCO3/Na2CO3, 0.05% NaN3, pH 9.6; 200 μL per well) at 4 °C overnight. All subsequent steps were carried out at room temperature. The plate was washed manually four times with 250 μL of washing buffer (50 mM NaH2PO4/Na2HPO4, 0.01% Tween 20, 0.05% NaN3, pH 7.4). The free binding sites in each well were blocked with 250 μL of 1% BSA in 50 mM NaH2PO4/Na2HPO4, 0.05% NaN3, pH 7.4 for 1 h. The plate was washed four times with washing buffer. Either standard dilutions of DCF in double distilled water or environmental samples (100 μL per well) were added, immediately followed by the anti-DCF monoclonal mouse antibody (12G5; optimal concentration, 0.225 μg mL–1 in 100 mM NaH2PO4/Na2HPO4, 300 mM NaCl, 100 μL per well) and incubated for 1 h. After four washing steps, the microtiter plate was incubated for 1 h with 100 μL of the IgG-UCNP conjugate (optimal concentration, 10 μg mL–1 in 50 mM Tris, 150 mM NaCl, 0.05% NaN3, 0.01% Tween 20, 0.05% BGG, 0.5% BSA, 0.2% PVA, pH 7.75). After four washing steps, the upconversion luminescence was read out from empty wells using a custom-built upconversion microplate reader (Chameleon multilabel microplate reader, Hidex, Turku, Finland) equipped with a continuous 980 nm laser (4 W). A collimated laser spot of ∼0.8 mm was focused on the bottom of the microtiter wells. Each well was scanned 100 times in a raster with the step size of 0.4 mm and 500 ms signal integration time. The truncated mean was calculated for each well after discarding the 10 highest and 10 lowest measurements of the luminescence intensity to account for local irregularities on the microtiter well surface that result in signal outliers.

Enzyme-Linked Immunosorbent Assay

The ELISA was performed as described earlier. (26) A transparent 96-well microtiter plate with high protein binding capacity (Greiner Bio-one, Frickenhausen, Germany) was coated with 0.5 μg mL–1 of ovalbumin-DCF conjugate in coating buffer (50 mM NaHCO3/Na2CO3, 0.05% NaN3, pH 9.6; 200 μL per well) at 4 °C overnight. All subsequent steps were carried out at room temperature. The plate was automatically washed with a plate washer (ELx405 Select, Bio-Tek Instruments, Bad Friedrichshall, Germany) four times with washing buffer (50 mM KH2PO4/K2HPO4, 146 mM NaCl, 0.05% Tween 20, pH 7.6; PBST). The free binding sites in each well were blocked with 300 μL of 1% BSA in PBST for 1 h. The plate was washed four times with washing buffer. First, standard dilutions of DCF in double distilled water or environmental samples (100 μL per well) were added, immediately followed by the anti-DCF monoclonal mouse antibody (12G5, 0.5 μg mL–1 in PBS; 100 μL per well) and incubated for 30 min. After four washing steps, the secondary horseradish peroxidase-labeled antibody was added (0.2 mg mL–1 in PBS; 200 μL per well) and incubated for 1 h. After final washing, the substrate solution (200 μL per well) was added and the plates were shaken for about 15 min for color development. The substrate solution consisted of 25 mL substrate buffer (prepared with 46.0 mL of potassium dihydrogen citrate and 0.1 g of potassium sorbate in 1 L of water, pH 3.8), 500 μL of 3,3′,5,5′-tetramethylbenzidine stock solution (375 mg in 30 mL of dimethyl sulfoxide), and 100 μL of 1% hydrogen peroxide. The enzyme reaction was stopped by adding 100 μL of 5% sulfuric acid per well. The absorbance was read at 450 nm by a microplate reader (Synergy HT, Bio-Tek Instruments).

Data Analysis

A four-parameter logistic function (eq 1) was used for a regression analysis of the calibration curves:(1)where [DCF] is the concentration of diclofenac, and Y is either the upconversion luminescence or the absorbance at 450 nm. Equation 1 yields the maximum (Ymax) and background (Ybg) signal, the DCF concentration that reduces (Ymax – Ybg) by 50% (IC50) and the slope at the inflection point (s). All measurements were made at least in triplicate. The concentration of DCF in real water samples was determined by utilizing an inverse function of eq 1 and the limit of detection (LOD) was defined as before: (26)(2)

Results and Discussion

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Surface Modification and Characterization of UCNPs

The development of a competitive upconversion immunoassay (ULISA) for the detection of DCF (Figure 1) critically depends on the design of the luminescent reporter that replaces the conventional enzyme amplification steps. (30) Oleic acid-capped UCNPs were coated with a silica shell exposing carboxylic acid functional groups on the surface. The carboxyl groups improve the dispersibility in water and serve as attachment sites for subsequent conjugation steps. We previously described a one-step water-in-oil microemulsion protocol for coating the surface of small UCNPs (∼12 nm in diameter) with a carboxylated silica shell that showed only a weak upconversion luminescence. (25) For the immunoassay, we have synthesized larger UCNPs of 42.5 ± 4.9 nm in diameter (Supporting Information Figure S1) that are much brighter because they are less affected by surface quenching effects. (31) The one step silica-coating protocol, however, resulted in aggregation when directly applied to bigger nanoparticles. Therefore, we developed a two-step protocol to prepare a thicker, compact, and more stable silica shell on the surface of UCNPs. (32) First, TEOS was added to the microemulsion to generate a thin layer of bare silica (2.4 ± 0.4 nm, Supporting Information Figure S2). This step alone was not sufficient to prevent aggregation. Therefore, TEOS was added for a second time, which changed the thickness of the silica shell only slightly. The second carboxylation step ensured an excellent dispersibility of COOH-UCNP in water. (33) The total diameter of COOH-UCNPs was consistent as determined by transmission electron microscopy (TEM, 46.9 ± 5.0 nm; Supporting Information Figure S3 and Figure 2A) and atomic force microscopy (AFM, 45.4 ± 7.6 nm; Supporting Information Figure S4). Dynamic light scattering measurements confirmed an increase of the hydrodynamic diameter from 55 to 65 nm after silica coating (Supporting Information Figure S5).

Figure 2

Figure 2. Preparation and characterization of IgG-UCNP conjugates. (A) TEM image of silica-coated UCNPs exposing carboxyl groups on the surface (COOH-UCNPs, Supporting Information Figure S3). (B) The carboxyl groups are activated by EDC/sulfo-NHS and conjugated to anti-mouse IgG. (C) The conjugates are prepared by using different ratios of anti-mouse IgG and COOH-UCNPs (I/II, 33 to 1; III/IV, 7 to 1; V/VI, 3 to 1; VII/VIII, no IgG). Each sample is centrifuged either with 4 000g (I, III, V, VII) or with 10 000g (II, IV, VI, VIII) and characterized by agarose gel electrophoresis. The migration distance (Δ) is indicated with red lines. (D) The relative electrophoretic mobility (Δratio[x]/Δno IgG) of the conjugates is linearly dependent on the ratio of IgG molecules per UCNP.

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The optimized COOH-UCNPs were then conjugated to a secondary anti-IgG antibody via standard EDC/sulfo-NHS chemistry (Figure 2B). (34, 35) A low concentration of COOH-UCNP was utilized to prevent that one antibody molecule binds to several UCNPs, which would lead to aggregation. The conjugates were characterized by agarose gel electrophoresis (Figure 2C), dynamic light scattering (DLS), zeta potential measurements, and FT-IR spectroscopy (Supporting Information Figures S6–S8). The lowest degree of aggregation was observed when the concentration of COOH-UCNPs in the reaction mixture was 1 mg mL–1. The conjugation of the secondary antibody reduced the negative surface potential of the COOH-UCNPs as shown by zeta potential measurements and led to a stronger retardation in the agarose gel. (36) The shift of the electrophoretic mobility was linearly dependent on the ratio of IgG molecules per UCNP and indicated the degree of surface modification (Figure 2D). Additionally, larger aggregates of nanoparticles remained in the gel pockets and could not enter the agarose matrix. Sample IgG-UCNP-33:1 shows a main fraction of monodisperse bioconjugates separated as a distinct band and a smaller fraction of slowly moving components, which are probably partially aggregated and cross-linked bioconjugates. This result is consistent with a bimodal particle distribution and a higher polydispersity index observed in the DLS measurement.
The IgG-UCNP conjugates were purified from an excess of unbound secondary anti-mouse IgG and components of the reaction mixture by differential centrifugation. At first, the bioconjugates were centrifuged at 10 000g, which however, led to strong nanoparticle aggregation (Figure 2C). When the centrifugal speed was reduced to 4 000g followed by short sonication, purified, and monodisperse IgG-UCNP were obtained. Further lowering of the centrifugal field was not efficient since the sedimentation of IgG-UCNP was too slow. The small retardation coefficient of UCNPs prepared with the lowest amount of IgG (IgG-UCNP-3:1, Figure 2C, lane V) indicated an insufficient surface modification. Therefore, this bioconjugate was not used for the following ULISA experiments.

Design of Upconversion-Linked Immunosorbent Assay

In a competitive immunoassay, a low concentration of coating antigen ensures that the free analyte can compete efficiently for the binding sites of the detection antibodies. On the other hand, the signal generation has to be strong enough for a reliable readout. Here, we prepared two different coating conjugates consisting of BSA-DCF. The conjugates were analyzed by MALDI-TOF mass spectrometry, which showed a coupling density of either 5.7 or 10 DCF residues per BSA molecule (Supporting Information Figures S9–S11). When the conjugate with the higher degree of derivatization was used for coating in the immunoassay, the signals were, as expected, about twice as high but also showed stronger signal fluctuation and a hook effect (Figure 3A), which may be the consequence of two binding sites of IgG molecules forming cyclic complexes (Supporting Information Figure S12). (37) By contrast, the conjugate exposing 5.7 DCF residues per BSA molecule yielded more stable signals and a slightly lower IC50 value (1.2 ng mL–1 compared to 1.5 ng mL–1) and a lower detection limit for DCF. Consequently, this coating conjugate was used in all further experiments. An optimal signal generation was observed with a coating concentration of 1 μg mL–1 (Supporting Information Figure S13).

Figure 3

Figure 3. ULISA optimization. (A) Microtiter plates are coated with 1 μg mL–1 of BSA carrying either 10 (red □) or 5.7 (○) DCF residues. (B) The upconversion luminescent (UCL) signal is generated by using 10 μg mL–1 of IgG-UCNP-33:1 (○) or IgG-UCNP-7:1 (red □), respectively. (C) The detection of DCF is optimized by using the monoclonal anti-DCF antibody in concentrations of 0.5 μg mL–1 (○) (IC50, 0.68 ng mL–1), 0.25 μg mL–1 (red □) (IC50, 0.23 ng mL–1), 0.1 μg mL–1 (blue △) (IC50, 0.13 ng mL–1) or 0.02 μg mL–1 (green ◇) (IC50, 0.08 ng mL–1). Error bars represent standard deviations in upconversion signals from three replicate wells.

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The competition step including free DCF and anti-DCF detection antibody was performed in analogy to a sensitive conventional ELISA. (26) Only the enzyme-mediated color generation was replaced by an IgG-UCNP conjugate as a direct luminescent reporter (Figure 3B). The higher degree of UCNP surface coverage (IgG-UCNP ratio of 33:1 compared to 7:1) increased the maximum signal intensity by a factor of 5 although both conjugates were prepared with a molar excess of IgG molecules per nanoparticle. This difference can be explained because not every surface-conjugated antibody may have the right orientation or be fully functional in order to bind efficiently to the primary antibody. Consequently, a higher degree of derivatization resulted in a proportionally higher number of functional antibodies. On the downside, using IgG-UCNP-33:1 resulted in strong signal fluctuations as well as a hook effect, which impedes the reproducible determination of DCF. It should also be noted that the degree of surface substitution did not significantly affect IC50 or the LOD, and a concentration of 10 μg mL–1 IgG-UCNP-7:1 resulted in the most reproducible upconversion signal generation (Supporting Information Figure S14).
In contrast to the UCNP-bound secondary antibody, the primary anti-DCF antibody is directly involved in the competition step. Figure 3C shows that both the upconversion signal intensity and the IC50/LOD for DCF strongly depend on the antibody concentration. A higher primary antibody concentration leads to a higher signal intensity because more antibodies can bind to the DCF-BSA coating conjugate, but they also consume a larger amount of free DCF and thus deteriorate the assay sensitivity. A concentration of 0.25 μg mL–1 primary anti-DCF antibody yielded an optimal balance between signal generation and sensitivity for the determination of DCF and was used in all further experiments.

Calibration and Sensitivity of ULISA and ELISA

For each type of competitive immunoassay, it is necessary to find the optimal balance between detection sensitivity for an analyte and signal development. It should also be noted that a high affinity and a low cross-reactivity of the primary antibody are the most distinctive features that determine the sensitivity and specificity of the analyte detection. Figure 4 shows calibration curves of ULISA and ELISA recorded under similar conditions and using the same anti-DCF primary antibody. In both cases a signal to background ratio (Ymax/Ybg) of 5:1 was adjusted to achieve the most sensitive detection of DCF but also to obtain a reliable signal generation. The competitive ULISA (LOD, 0.05 ng mL–1/170 pM) has a 5 times higher detection limit than a conventional ELISA (LOD, 0.01 ng mL–1/ 34 pM) but allows for an easier and faster signal generation. As the detection sensitivity is ultimately dependent on the anti-DCF antibody, it can be expected that the ULISA can be further optimized by developing brighter UCNPs reporter conjugates.

Figure 4

Figure 4. Normalized calibration curves of ULISA (red □, replotted red curve from Figure 3C; IC50, 0.23 ng mL–1; LOD, 0.05 ng mL–1) and ELISA (○, IC50, 0.05 ng mL–1; LOD, 0.01 ng mL–1). Error bars represent standard deviations of three replicate wells.

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Competitive immunoassays for small molecules are typically less sensitive than sandwich immunoassays where the signal generation is directly proportional to the analyte concentration. The highest sensitivity was described for the detection of Schistosoma circulating anodic antigen by using micrometer-sized upconversion particles in a lateral flow assay (LOD, 0.01 ng mL–1/0.1 pM). (13) This particular analyte displays repetitive surface epitopes and facilitates binding of several primary antibodies per analyte molecule. The competitive immunoassay for DCF affords a similar sensitivity as a magnetic bead-based competitive immunoassay for the detection of aflatoxin that was reported to reach an LOD of 0.01 ng mL–1 (50 pM) under optimal conditions. (16) The additional magnetic separation step, however, demands a more sophisticated instrumentation and is more time-consuming.

Detection of Diclofenac in Real Water Samples

Two surface water samples and drinking water were collected in Southern Bavaria and the matrix was analyzed (Supporting Information Table S1) to assess possible interferences with the detection of DCF. These interferences should be as low as possible because matrix effects can suppress the immunoassay signal and lead to an overestimation of analyte concentrations. The monoclonal primary antibody 12G5 is resistant to matrix interferences over a wide pH range, humic acid concentrations up 20 mg L–1, and Ca2+ concentrations up to 75 mg L–1 as described earlier. (26) The drinking water sample from Munich, however, contained relatively high Ca2+ and Mg2+ concentrations of 110 mg L–1 in total, which is probably the reason for a signal suppression (defined as 100 × (Ysample – Ybg)/(Ymax – Ybg)) to 60 ± 7% in the ULISA and 73 ± 10% in the ELISA in the undiluted samples without DCF. By contrast, the surface water samples contained less Ca2+ and Mg2+ and were less affected by signal suppression.
The concentration of DCF was too low to be detectable in the unspiked water samples. Thus, each sample was additionally spiked with either 1 ng mL–1 or 10 ng mL–1 of DCF. The spiked samples were typically diluted at least by a factor of 3 prior to the immunoassay to keep matrix effects to a minimum. Table 1 shows the concentrations of DCF as determined by ULISA, ELISA, and LC–MS. The ULISA led to slightly stronger deviations from the spiking concentration compared to the ELISA because the matrix may also have an impact on the binding of the nanoparticulate luminescent reporter unit, which is relatively large compared to the enzyme antibody conjugate used for the ELISA. These differences in the immunoassay performance are subject to further investigation and will be optimized to unfold the full potential of the ULISA for the background-free detection of analytes.
Table 1. Detection of DCF in Unspiked and Spiked Real Water Samples
samplespiked (ng mL–1)ULISA (ng mL–1)ELISA (ng mL–1)LC–MS (ng mL–1)
  <LOD<LOD<LOD
Lake Wörthsee11.81 ± 0.061.11 ± 0.261.1 ± 0.09
 1010.2 ± 3.89.9 ± 1.58.2 ± 0.7
     
  <LOD<LOD<LOD
Würm River11.05 ± 0.261.16 ± 0.041.30 ± 0.35
 1010.9 ± 1.611.9 ± 1.58.7 ± 0.8
     
  <LOD<LOD<LOD
Munich tap water11.53 ± 0.281.06 ± 0.011.32 ± 0.10
 1015.0 ± 5.410.3 ± 1.68.9 ± 0.2

Conclusion

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The first immunoassays employed radionuclides that are very small, can be directly attached to the tracer or detection antibody, and generate a signal without background interference. Radioimmunoassays, however, have been largely replaced by ELISAs because of shorter signal acquisition times, lower costs, and safety considerations. Compared to the fluorescent immunoassay (FIA), the ELISA is typically preferred because the enzyme-mediated signal amplification results in a lower background signal. As a new assay format, the competitive ULISA can achieve simultaneously a highly sensitive and background-free detection of analytes without the need for enzyme-mediated signal amplification. The design of the luminescent IgG-UCNP conjugate turned out to be critical in order to yield the most robust readout and the lowest detection limit for the environmental pollutant DCF (0.05 ng mL–1). It is expected that further control over nanoparticle bioconjugation, e.g., by optimizing the orientation of IgG molecules on the nanoparticle surface, and enhancing the brightness of UCNPs will allow to reach (or even surpass) the detection limit of conventional ELISAs.

Supporting Information

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The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.analchem.6b01083.

  • Synthesis of UCNPs, calculation of nanoparticle concentrations, TEM and AFM images, DLS and zeta potential measurement, FT-IR spectra, MALDI-TOF analyses, explanation of the hook effect, optimization of the ULISA, and characterization of water samples (PDF)

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Author Information

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  • Corresponding Author
    • Hans H. Gorris - Institute of Analytical Chemistry, Chemo- and Biosensors, University of Regensburg, 93040 Regensburg, Germany;  Email: [email protected]
  • Authors
    • Antonín Hlaváček - Institute of Analytical Chemistry, Chemo- and Biosensors, University of Regensburg, 93040 Regensburg, Germany;  CEITEC−Central European Institute of Technology, Masaryk University, Brno 625 00, Czech Republic;  Institute of Analytical Chemistry AS CR, v. v. i., Brno 602 00, Czech Republic
    • Zdeněk Farka - Institute of Analytical Chemistry, Chemo- and Biosensors, University of Regensburg, 93040 Regensburg, Germany;  CEITEC−Central European Institute of Technology, Masaryk University, Brno 625 00, Czech Republic
    • Maria Hübner - Chair of Analytical Chemistry and Institute of Hydrochemistry, Technical University of Munich, 81377 Munich, Germany
    • Veronika Horňáková - CEITEC−Central European Institute of Technology, Masaryk University, Brno 625 00, Czech Republic
    • Daniel Němeček - CEITEC−Central European Institute of Technology, Masaryk University, Brno 625 00, Czech Republic
    • Reinhard Niessner - Chair of Analytical Chemistry and Institute of Hydrochemistry, Technical University of Munich, 81377 Munich, Germany
    • Petr Skládal - CEITEC−Central European Institute of Technology, Masaryk University, Brno 625 00, Czech Republic
    • Dietmar Knopp - Chair of Analytical Chemistry and Institute of Hydrochemistry, Technical University of Munich, 81377 Munich, Germany
  • Notes
    The authors declare no competing financial interest.

Acknowledgment

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We thank Prof. Rainer Deutzmann for performing MALDI-TOF experiments and Manuel Schrottenbaum for supporting the nanoparticle bioconjugation. We acknowledge financial support from the COST Action CM1403 “The European Upconversion Network: From the Design of Photon-Upconverting Nanomaterials to Biomedical Applications”. H.H.G. acknowledges funding from the German Research Foundation for a Heisenberg Fellowship (DFG, Grant GO 1968/5-1). The project was further funded by the Program of “Employment of Newly Graduated Doctors of Science for Scientific Excellence” (Grant CZ.1.07/2.3.00/30.0009), the Czech Ministry of Education, Youth and Sports (COST CZ Project LD15023), ANR-DFG program (Project NArBioS, Grant No. ANR-11-INTB-1013), and the German Academic Exchange Service (DAAD). At the Institute of Analytical Chemistry AS CR, v. v. i, the project was supported by Grant Agency of the Czech Republic (Grant Number 14-28254S).

References

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This article references 37 other publications.

  1. 1
    Wang, L.; Wang, K. M.; Santra, S.; Zhao, X. J.; Hilliard, L. R.; Smith, J. E.; Wu, J. R.; Tan, W. H. Anal. Chem. 2006, 78, 646– 654 DOI: 10.1021/ac0693619
    Google Scholar
    There is no corresponding record for this reference.
  2. 2
    Jans, H.; Huo, Q. Chem. Soc. Rev. 2012, 41, 2849– 2866 DOI: 10.1039/C1CS15280G
    Google Scholar
    There is no corresponding record for this reference.
  3. 3
    Osterfeld, S. J.; Yu, H.; Gaster, R. S.; Caramuta, S.; Xu, L.; Han, S. J.; Hall, D. A.; Wilson, R. J.; Sun, S. H.; White, R. L.; Davis, R. W.; Pourmand, N.; Wang, S. X. Proc. Natl. Acad. Sci. U. S. A. 2008, 105, 20637– 20640 DOI: 10.1073/pnas.0810822105
    Google Scholar
    There is no corresponding record for this reference.
  4. 4
    Čunderlová, V.; Hlaváček, A.; Horňáková, V.; Peterek, M.; Němeček, D.; Hampl, A.; Eyer, L.; Skládal, P. Microchim. Acta 2016, 183, 651– 658 DOI: 10.1007/s00604-015-1697-z
    Google Scholar
    4
    Catalytic nanocrystalline coordination polymers as an efficient peroxidase mimic for labeling and optical immunoassays
    Cunderlova, Veronika; Hlavacek, Antonin; Hornakova, Veronika; Peterek, Miroslav; Nemecek, Daniel; Hampl, Ales; Eyer, Ludek; Skladal, Petr
    Microchimica Acta (2016), 183 (2), 651-658CODEN: MIACAQ; ISSN:0026-3672. (Springer-Verlag GmbH)
    We report that nanocryst. Prussian blue of the type Fe4[Fe(CN)6]3 is a powerful peroxidase mimic for use in labeling of biomols. The cubic nanocrystals typically have a diam. of 15 nm and are capable of catalyzing the oxidn. of colorless 3,3,5,5-tetramethylbenzidine in the presence of H2O2 to form an intensively colored product with an absorption max. at 662 nm. The detd. pseudo turnover no. is ∼20,000 s-1 which is the highest value reported for nanoparticles of a size comparable to common proteins. We also present a method for the biotinylation of the surface of these nanocrystals, and show their use in competitive bioaffinity based assays of biotin and human serum albumin. The limits of detection are 0.35 and 0.27μg mL-1, resp. The results prove the applicability of coordination polymers for signal amplification and also their compatibility with the format of enzyme linked immunosorbent assays.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXitVagtbjN&md5=aba8a56c6dba25e54b186016f1a9fe12
  5. 5
    Hlaváček, A.; Bouchal, P.; Skládal, P. Microchim. Acta 2012, 176, 287– 293 DOI: 10.1007/s00604-011-0729-6
    Google Scholar
    5
    Biotinylation of quantum dots for application in fluoroimmunoassays with biotin-avidin amplification
    Hlavacek, Antonin; Bouchal, Pavel; Skladal, Petr
    Microchimica Acta (2012), 176 (3-4), 287-293CODEN: MIACAQ; ISSN:0026-3672. (SpringerWienNewYork)
    A competitive microplate fluoroimmunoassay was developed for the detn. of human serum albumin in urine. It is based on the use of biotinylated CdTe quantum dots (QDs) whose synthesis is optimized in terms of storage stability, purifn., and signal-to-noise ratio. The bioconjugated QDs were characterised by gel chromatog. and gel electrophoresis. Storage stability and quantum yield were investigated. The excitation/emission wavelengths are 360/620 nm. The immunoassay of human serum albumin in urine has a working range from 1.7 to 10 μg.mL-1, and the limit of detection is 1.0 μg.mL-1.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhsVWktL8%253D&md5=ec11aa982b187d8ce48097a304ea98a2
  6. 6
    Auzel, F. Chem. Rev. 2004, 104, 139– 173 DOI: 10.1021/cr020357g
    Google Scholar
    6
    Upconversion and Anti-Stokes Processes with f and d Ions in Solids
    Auzel, Francois
    Chemical Reviews (Washington, DC, United States) (2004), 104 (1), 139-173CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)
    A review. Topics include: role of energy diffusion in up and down-conversion in energy transfers between rare earth ions; upconversion in a single-ion level description for APTE (i.e., energy transfer upconversion) or excited state absorption (ESA) and in a pair-level one; upconversion studies in lanthanide and actinide ion-doped solids and transition-metal ion-doped solids with APTE and ESA processes; cross-relaxation and the photon avalanche effect; APTE for display and IR detection; APTE and ESA pumped lasers; perspective and future advances in upconversion UV-tunable lasers, in IR imaging, bistability, hot emission and avalanche like codoped systems, and biol. applications.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXovFOhtb4%253D&md5=64dd0339b3dcfa5ef4dc4c7072dc3992
  7. 7
    Haase, M.; Schäfer, H. Angew. Chem., Int. Ed. 2011, 50, 5808– 5829 DOI: 10.1002/anie.201005159
    Google Scholar
    7
    Upconverting Nanoparticles
    Haase, Markus; Schaefer, Helmut
    Angewandte Chemie, International Edition (2011), 50 (26), 5808-5829CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
    A review. Upconversion (UC) refers to nonlinear optical processes in which the sequential absorption of two or more photons leads to the emission of light at shorter wavelength than the excitation wavelength (anti-Stokes type emission). In contrast to other emission processes based on multiphoton absorption, upconversion can be efficiently excited even at low excitation densities. The most efficient UC mechanisms are present in solid-state materials doped with rare-earth ions. The development of nanocrystal research has evoked increasing interest in the development of synthesis routes which allow the synthesis of highly efficient, small UC particles with narrow size distribution able to form transparent solns. in a wide range of solvents. Meanwhile, high-quality UC nanocrystals can be routinely synthesized and their soly., particle size, crystallog. phase, optical properties and shape can be controlled. In recent years, these particles have been discussed as promising alternatives to org. fluorophosphors and quantum dots in the field of medical imaging.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXmvVent74%253D&md5=6ca41c83f4d6c6f3e9193ae6f07c344a
  8. 8
    Ehlert, O.; Thomann, R.; Darbandi, M.; Nann, T. ACS Nano 2008, 2, 120– 124 DOI: 10.1021/nn7002458
    Google Scholar
    There is no corresponding record for this reference.
  9. 9
    Li, X. M.; Zhang, F.; Zhao, D. Y. Chem. Soc. Rev. 2015, 44, 1346– 1378 DOI: 10.1039/C4CS00163J
    Google Scholar
    9
    Lab on upconversion nanoparticles: optical properties and applications engineering via designed nanostructure
    Li, Xiaomin; Zhang, Fan; Zhao, Dongyuan
    Chemical Society Reviews (2015), 44 (6), 1346-1378CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)
    A review. Over the past decade, high-quality lanthanide doped upconverting nanoparticles (UCNPs) have been successfully synthesized with the rapid development of nanotechnol. Due to the unique electron configuration of lanthanide ions, there are rich energy level structures in the near-IR, visible and UV spectral range. However, for UCNPs, only a limited no. of efficient upconversion excitation and emission have been generated due to the limited no. of sensitizer (Yb3+) and activator (Tm3+, Er3+, and Ho3+) ions, and the application is mainly focused on the bio-imaging by using the upconversion luminescence of UCNPs. Recently, more and more researchers have started to focus on tuning of upconversion optical properties and developing of multi-functional UCNPs by using the combination of sub-lattice mediated energy migration, core@shell structural engineering and UCNPs based nanocomposites which greatly expands the range of applications for lanthanide-doped UCNPs. Therefore, a "nanolab" can be created on UCNPs, where the property modulation can be realized via the designed host-dopants combinations, core@shell nanostructure, energy exchange with "alien species" (org. dyes, quantum dots, etc.), and so on. In this paper, we provide a comprehensive survey of the latest advances made in developing lanthanide-doped UCNPs, which include excitation and emission energy levels guided designing of the UCNP nanostructure, the synthesis techniques to fabricate the nanostructure with optimum energy level structure and optical properties, the fabrication of UCNPs-based nanocomposites to extend the applications by introducing the addnl. functional components, or integrating the functional moiety into one nanocomposite.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXht1SlurbJ&md5=33edd049727843cc45b056f366a2931a
  10. 10
    Gorris, H. H.; Ali, R.; Saleh, S. M.; Wolfbeis, O. S. Adv. Mater. 2011, 23, 1652– 1655 DOI: 10.1002/adma.201004697
    Google Scholar
    There is no corresponding record for this reference.
  11. 11
    Päkkilä, H.; Ylihärsilä, M.; Lahtinen, S.; Hattara, L.; Salminen, N.; Arppe, R.; Lastusaari, M.; Saviranta, P.; Soukka, T. Anal. Chem. 2012, 84, 8628– 8634 DOI: 10.1021/ac301719p
    Google Scholar
    There is no corresponding record for this reference.
  12. 12
    Huang, P.; Zheng, W.; Zhou, S. Y.; Tu, D. T.; Chen, Z.; Zhu, H. M.; Li, R. F.; Ma, E.; Huang, M. D.; Chen, X. Y. Angew. Chem., Int. Ed. 2014, 53, 1252– 1257 DOI: 10.1002/anie.201309503
    Google Scholar
    There is no corresponding record for this reference.
  13. 13
    Corstjens, P. L. A. M.; van Lieshout, L.; Zuiderwijk, M.; Kornelis, D.; Tanke, H. J.; Deelder, A. M.; van Dam, G. J. J. Clin. Microbiol. 2008, 46, 171– 176 DOI: 10.1128/JCM.00877-07
    Google Scholar
    13
    Up-converting phosphor technology-based lateral flow assay for detection of Schistosoma Circulating anodic antigen in serum
    Corstjens, Paul L. A. M.; van Lieshout, Lisette; Zuiderwijk, Michael; Kornelis, Dieuwke; Tanke, Hans J.; Deelder, Andre M.; van Dam, Govert J.
    Journal of Clinical Microbiology (2008), 46 (1), 171-176CODEN: JCMIDW; ISSN:0095-1137. (American Society for Microbiology)
    Schistosoma sp. circular anodic antigen (CAA) serum concns. reflect actual worm burden in a patient and are a valuable tool for population screening and epidemiol. research. However, for the diagnosis of individual imported schistosomiasis cases, the current ELISA lacks sensitivity and robustness. Therefore, a lateral flow (LF) assay was developed to test CAA in serum for individual diagnosis of imported active schistosome infections. Application of fluorescent submicron-sized up-converting phosphor technol. (UPT) reporter particles increased anal. sensitivity compared to that of the std. ELISA method. Evaluation of the UPT-LF test with a selection of 40 characterized epidemiol. samples indicated a good correlation between signal intensity and infection intensity. Subsequently, the UPT-LF assay was applied to 166 serum samples of Dutch residents (immigrants and travelers) suspected of schistosomiasis, a case in which group routine antibody detection frequently fails straightforward diagnosis. The UPT-LF assay identified 36 CAA-pos. samples, compared to 15 detected by CAA-ELISA. In conclusion, the UPT-LF assay is a low-complexity test with higher sensitivity than the CAA-ELISA, well suited for lab. diagnosis of individual active Schistosoma infections.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXhs1aqtb0%253D&md5=d94369811b333fb839727192b91b4b05
  14. 14
    Kuningas, K.; Päkkilä, H.; Ukonaho, T.; Rantanen, T.; Lövgren, T.; Soukka, T. Clin. Chem. 2007, 53, 145– 146 DOI: 10.1373/clinchem.2006.076687
    Google Scholar
    14
    Upconversion fluorescence enables homogeneous immunoassay in whole blood
    Kuningas, Katri; Pakkila, Henna; Ukonaho, Telle; Rantanen, Terhi; Lovgren, Timo; Soukka, Tero
    Clinical Chemistry (Washington, DC, United States) (2007), 53 (1), 145-146CODEN: CLCHAU; ISSN:0009-9147. (American Association for Clinical Chemistry)
    A competitive homogeneous immunoassay for 17β-estradiol was employed in whole blood as a model to demonstrate the application of upconversion fluorescence resonance energy transfer (FRET) using a near-IR fluorescent acceptor dye. Because of the relatively transparency of blood to light at wavelengths above 650 nm, the excitation of the up-converting phosphor (UCP) was not attenuated. The measurement of the sensitized acceptor emission above 700 nm completely eliminates the background arising from blood and from possible donor emission, even without temporal resoln. in fluorescence detection. Moreover, in the upconversion FRET-based assay, no emission from the acceptor alone is produced upon IR excitation. The assay is relatively simple and can be performed in a std. microtiter plate assay format using uncomplicated detection instrument.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXmsFGhtA%253D%253D&md5=e098335f71b587b1175f3b25fa1df759
  15. 15
    Arppe, R.; Mattsson, L.; Korpi, K.; Blom, S.; Wang, Q.; Riuttamaki, T.; Soukka, T. Anal. Chem. 2015, 87, 1782– 1788 DOI: 10.1021/ac503691m
    Google Scholar
    There is no corresponding record for this reference.
  16. 16
    Wu, S. J.; Duan, N.; Zhu, C. Q.; Ma, X. Y.; Wang, M.; Wang, Z. P. Biosens. Bioelectron. 2011, 30, 35– 42 DOI: 10.1016/j.bios.2011.08.023
    Google Scholar
    There is no corresponding record for this reference.
  17. 17
    Ternes, T. A. TrAC, Trends Anal. Chem. 2001, 20, 419– 434 DOI: 10.1016/S0165-9936(01)00078-4
    Google Scholar
    There is no corresponding record for this reference.
  18. 18
    Perez, S.; Barcelo, D. TrAC, Trends Anal. Chem. 2007, 26, 494– 514 DOI: 10.1016/j.trac.2007.05.004
    Google Scholar
    There is no corresponding record for this reference.
  19. 19
    Oaks, J. L.; Gilbert, M.; Virani, M. Z.; Watson, R. T.; Meteyer, C. U.; Rideout, B. A.; Shivaprasad, H. L.; Ahmed, S.; Chaudhry, M. J. I.; Arshad, M.; Mahmood, S.; Ali, A.; Khan, A. A. Nature 2004, 427, 630– 633 DOI: 10.1038/nature02317
    Google Scholar
    There is no corresponding record for this reference.
  20. 20
    Koutsouba, V.; Heberer, T.; Fuhrmann, B.; Schmidt-Baumler, K.; Tsipi, D.; Hiskia, A. Chemosphere 2003, 51, 69– 75 DOI: 10.1016/S0045-6535(02)00819-6
    Google Scholar
    There is no corresponding record for this reference.
  21. 21
    Heberer, T. Toxicol. Lett. 2002, 131, 5– 17 DOI: 10.1016/S0378-4274(02)00041-3
    Google Scholar
    21
    Occurrence, fate, and removal of pharmaceutical residues in the aquatic environment: a review of recent research data
    Heberer, Thomas
    Toxicology Letters (2002), 131 (1-2), 5-17CODEN: TOLED5; ISSN:0378-4274. (Elsevier Science Ireland Ltd.)
    A review is given. The occurrence and fate of pharmaceutically active compds. (PhACs) in the aquatic environment has been recognized as one of the emerging issues in environmental chem. In some studies carried out in Austria, Brazil, Canada, Croatia, England, Germany, Greece, Italy, Spain, Switzerland, the Netherlands, and the US, >80 compds., pharmaceuticals and several drug metabolites, have been detected in the aquatic environment. Several PhACs from various prescription classes have been found at concns. up to the μg/L-level in sewage influent and effluent samples and also in several surface waters located downstream from municipal sewage treatment plants (STPs). The studies show that some PhACs originating from human therapy are not eliminated completely in the municipal STPs and are, thus, discharged as contaminants into the receiving waters. Under recharge conditions, polar PhACs such as clofibric acid, carbamazepine, primidone or iodinated contrast agents can leach through the subsoil and have also been detected in several groundwater samples in Germany. Pos. findings of PhACs have, however, also been reported in groundwater contaminated by landfill leachates or manufg. residues. To date, only in a few cases PhACs have also been detected at trace-levels in drinking water samples.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38Xjt1Wju7s%253D&md5=e7d40a736848a1ebfac9df2188a27891
  22. 22
    Sacher, F.; Lange, F. T.; Brauch, H. J.; Blankenhorn, I. J. Chromatogr. A 2001, 938, 199– 210 DOI: 10.1016/S0021-9673(01)01266-3
    Google Scholar
    There is no corresponding record for this reference.
  23. 23
    Petrovic, M.; Hernando, M. D.; Diaz-Cruz, M. S.; Barcelo, D. J. Chromatogr. A 2005, 1067, 1– 14 DOI: 10.1016/j.chroma.2004.10.110
    Google Scholar
    There is no corresponding record for this reference.
  24. 24
    Deng, A. P.; Himmelsbach, M.; Zhu, Q. Z.; Frey, S.; Sengl, M.; Buchberger, W.; Niessner, R.; Knopp, D. Environ. Sci. Technol. 2003, 37, 3422– 3429 DOI: 10.1021/es0341945
    Google Scholar
    There is no corresponding record for this reference.
  25. 25
    Hlaváček, A.; Sedlmeier, A.; Skládal, P.; Gorris, H. H. ACS Appl. Mater. Interfaces 2014, 6, 6930– 6935 DOI: 10.1021/am500732y
    Google Scholar
    There is no corresponding record for this reference.
  26. 26
    Huebner, M.; Weber, E.; Niessner, R.; Boujday, S.; Knopp, D. Anal. Bioanal. Chem. 2015, 407, 8873– 8882 DOI: 10.1007/s00216-015-9048-9
    Google Scholar
    26
    Rapid analysis of diclofenac in freshwater and wastewater by a monoclonal antibody-based highly sensitive ELISA
    Huebner, Maria; Weber, Ekkehard; Niessner, Reinhard; Boujday, Souhir; Knopp, Dietmar
    Analytical and Bioanalytical Chemistry (2015), 407 (29), 8873-8882CODEN: ABCNBP; ISSN:1618-2642. (Springer)
    The non-steroidal anti-inflammatory drug (NSAID) diclofenac (DCF) is found worldwide in the aq. environment. Therefore, it has raised increased public concern on potential long-term impact on human health and wildlife. The importance of DCF has been emphasized by the European Union recently by including this pharmaceutical in the first watch list of priority hazardous substances in order to gather Union-wide monitoring data. Rapid and cheap methods of anal. are therefore required for fresh and wastewater monitoring with high sample load. Here, for the first time, well-characterized monoclonal antibodies (mAbs) against DCF were generated and a highly sensitive ELISA developed. The best antibody (mAb 12G5) is highly affine (KD = 1.5 × 10-10 M), stable to potential matrix interferences such as pH value (pH range 5.2-9.2), calcium ion concn. (up to 75 mg/L), and humic acid content (up to 20 mg/L). The limit of detection (LOD, S/N = 3) and IC50 of the ELISA calibration curve were 7.8 and 44 ng/L, resp. The working range was defined between 11 and 180 ng/L. On av., about 10 % cross-reactivity (CR) was found for DCF metabolites 5-OH-DCF, 4'-OH-DCF, and DCF-acyl glucuronide, but other structurally related NSAIDs showed binding <1 % compared to the parent compd. While DCF concns. at the low ppt range were measured in river and lake water, higher values of 2.9 and 2.1 μg/L were found in wastewater influents and effluents, resp. These results could be confirmed by solid phase extn. combined with LC-MS.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhs1elsLvE&md5=03a86d51982229a7eeef982e2741f4d7
  27. 27
    Wang, F.; Han, Y.; Lim, C. S.; Lu, Y. H.; Wang, J.; Xu, J.; Chen, H. Y.; Zhang, C.; Hong, M. H.; Liu, X. G. Nature 2010, 463, 1061– 1065 DOI: 10.1038/nature08777
    Google Scholar
    There is no corresponding record for this reference.
  28. 28
    Schneider, C. A.; Rasband, W. S.; Eliceiri, K. W. Nat. Methods 2012, 9, 671– 675 DOI: 10.1038/nmeth.2089
    Google Scholar
    28
    NIH Image to ImageJ: 25 years of image analysis
    Schneider, Caroline A.; Rasband, Wayne S.; Eliceiri, Kevin W.
    Nature Methods (2012), 9 (7_part1), 671-675CODEN: NMAEA3; ISSN:1548-7091. (Nature Publishing Group)
    For the past 25 years NIH Image and ImageJ software have been pioneers as open tools for the anal. of scientific images. We discuss the origins, challenges and solns. of these two programs, and how their history can serve to advise and inform other software projects.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtVKntb7P&md5=85ab928cd79f1e2f2351c834c0c600f0
  29. 29
    Sedlmeier, A.; Hlavacek, A.; Birner, L.; Mickert, M. J.; Muhr, V.; Hirsch, T.; Corstjens, P. L.; Tanke, H. J.; Soukka, T.; Gorris, H. H. Anal. Chem. 2016, 88, 1835– 1841 DOI: 10.1021/acs.analchem.5b04147
    Google Scholar
    There is no corresponding record for this reference.
  30. 30
    Liebherr, R. B.; Soukka, T.; Wolfbeis, O. S.; Gorris, H. H. Nanotechnology 2012, 23, 485103 DOI: 10.1088/0957-4484/23/48/485103
    Google Scholar
    There is no corresponding record for this reference.
  31. 31
    Arppe, R.; Hyppänen, I.; Perälä, N.; Peltomaa, R.; Kaiser, M.; Würth, C.; Christ, S.; Resch-Genger, U.; Schäferling, M.; Soukka, T. Nanoscale 2015, 7, 11746– 11757 DOI: 10.1039/C5NR02100F
    Google Scholar
    There is no corresponding record for this reference.
  32. 32
    Wong, Y. J.; Zhu, L.; Teo, W. S.; Tan, Y. W.; Yang, Y.; Wang, C.; Chen, H. J. Am. Chem. Soc. 2011, 133, 11422– 11425 DOI: 10.1021/ja203316q
    Google Scholar
    32
    Revisiting the Stober Method: Inhomogeneity in Silica Shells
    Wong, Yi Jian; Zhu, Liangfang; Teo, Wei Shan; Tan, Yan Wen; Yang, Yanhui; Wang, Chuan; Chen, Hongyu
    Journal of the American Chemical Society (2011), 133 (30), 11422-11425CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
    The SiO2 shell on nanoparticles formed by a typical Stober method is inhomogeneous. The outer layer of the shell is chem. more robust than the inner layer, which can be selectively etched by hot H2O. Methods are developed to harden the soft SiO2 shells. These new understandings are exploited to develop versatile and template-free approaches for fabricating sophisticated yolk-shell nanostructures.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXovVehurY%253D&md5=efdd335fea50aac6298b8c3ca73cbb95
  33. 33
    Bagwe, R. P.; Hilliard, L. R.; Tan, W. H. Langmuir 2006, 22, 4357– 4362 DOI: 10.1021/la052797j
    Google Scholar
    There is no corresponding record for this reference.
  34. 34
    Algar, W. R.; Prasuhn, D. E.; Stewart, M. H.; Jennings, T. L.; Blanco-Canosa, J. B.; Dawson, P. E.; Medintz, I. L. Bioconjugate Chem. 2011, 22, 825– 858 DOI: 10.1021/bc200065z
    Google Scholar
    34
    The Controlled Display of Biomolecules on Nanoparticles: A Challenge Suited to Bioorthogonal Chemistry
    Algar, W. Russ; Prasuhn, Duane E.; Stewart, Michael H.; Jennings, Travis L.; Blanco-Canosa, Juan B.; Dawson, Philip E.; Medintz, Igor L.
    Bioconjugate Chemistry (2011), 22 (5), 825-858CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
    A review. Interest in developing diverse nanoparticle (NP)-biol. composite materials continues to grow almost unabated. This is motivated primarily by the desire to simultaneously exploit the properties of both NP and biol. components in new hybrid devices or materials that can be applied in areas ranging from energy harvesting and nanoscale electronics to biomedical diagnostics. The utility and effectiveness of these composites will be predicated on the ability to assemble these structures with control over NP/biomol. ratio, biomol. orientation, biomol. activity, and the sepn. distance within the NP-bioconjugate architecture. This degree of control will be esp. crit. in creating theranostic NP-bioconjugates that, as a single vector, are capable of multiple functions in vivo, including targeting, image contrast, biosensing, and drug delivery. In this review, a perspective is given on current and developing chemistries that can provide improved control in the prepn. of NP-bioconjugates. The nanoscale properties intrinsic to several prominent NP materials are briefly described to highlight the motivation behind their use. NP materials of interest include quantum dots, carbon nanotubes, viral capsids, liposomes, and NPs composed of gold, lanthanides, silica, polymers, or magnetic materials. This review includes a crit. discussion on the design considerations for NP-bioconjugates and the unique challenges assocd. with chem. at the biol.-nanoscale interface-the liabilities of traditional bioconjugation chemistries being particularly prominent therein. Select bioorthogonal chemistries that can address these challenges are reviewed in detail, and include chemoselective ligations (e.g., hydrazone and Staudinger ligation), cycloaddn. reactions in click chem. (e.g., azide-alkyne cyclyoaddn., tetrazine ligation), metal-affinity coordination (e.g., polyhistidine), enzyme driven modifications (e.g., HaloTag, biotin ligase), and other site-specific chemistries. The benefits and liabilities of particular chemistries are discussed by highlighting relevant NP-bioconjugation examples from the literature. Potential chemistries that have not yet been applied to NPs are also discussed, and an outlook on future developments in this field is given.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXmtVCntb0%253D&md5=df8646d15ead941699bccc3c174fff98
  35. 35
    Sedlmeier, A.; Gorris, H. H. Chem. Soc. Rev. 2015, 44, 1526– 1560 DOI: 10.1039/C4CS00186A
    Google Scholar
    35
    Surface modification and characterization of photon-upconverting nanoparticles for bioanalytical applications
    Sedlmeier, Andreas; Gorris, Hans H.
    Chemical Society Reviews (2015), 44 (6), 1526-1560CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)
    A review. Photon-upconverting nanoparticles (UCNPs) can be excited by near-IR light and emit visible light (anti-Stokes emission) which prevents autofluorescence and light scattering of biol. samples. The potential for background-free imaging has attracted wide interest in UCNPs in recent years. Small and homogeneous lanthanide-doped UCNPs that display high upconversion efficiency have typically been synthesized in org. solvents. Bioanal. applications, however, require a subsequent phase transfer to aq. solns. Hence, the surface properties of UCNPs must be well designed and characterized to grant both a stable aq. colloidal dispersion and the ability to conjugate biomols. and other ligands on the nanoparticle surface. In this review, we introduce various routes for the surface modification of UCNPs and critically discuss their advantages and disadvantages. The last part covers various anal. methods that enable a thorough examn. of the progress and success of the surface functionalization.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsVGjur7K&md5=103ff17432cb75c8fa71ea384111f65e
  36. 36
    Sapsford, K. E.; Tyner, K. M.; Dair, B. J.; Deschamps, J. R.; Medintz, I. L. Anal. Chem. 2011, 83, 4453– 4488 DOI: 10.1021/ac200853a
    Google Scholar
    36
    Analyzing Nanomaterial Bioconjugates: A Review of Current and Emerging Purification and Characterization Techniques
    Sapsford, Kim E.; Tyner, Katherine M.; Dair, Benita J.; Deschamps, Jeffrey R.; Medintz, Igor L.
    Analytical Chemistry (Washington, DC, United States) (2011), 83 (12), 4453-4488CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)
    A review with major sections on purifn., characterization (sepn. techniques, scattering techniques, microscopy, and spectroscopy), modeling, and emerging technologies and instrumentation.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXls1ekt7w%253D&md5=0a45ab29e7a9e9003899247720acd8e5
  37. 37
    Barbarakis, M. S.; Qaisi, W. G.; Daunert, S.; Bachas, L. G. Anal. Chem. 1993, 65, 457– 460 DOI: 10.1021/ac00052a024
    Google Scholar
    There is no corresponding record for this reference.

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  19. Xiuli Fu, Lingxin Chen, and Jaebum Choo . Optical Nanoprobes for Ultrasensitive Immunoassay. Analytical Chemistry 2017, 89 (1) , 124-137. https://doi.org/10.1021/acs.analchem.6b02251
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  31. Abhijit Hazra, Amita Mondal, Suparna Paul, Sourav Bej, Udayan Mondal, Somrita Nag, Priyabrata Banerjee. Chemosensing technology for rapid detection of emerging contaminants. 2022, 407-464. https://doi.org/10.1016/B978-0-323-85160-2.00013-5
  32. Simone Rink, Axel Duerkop, Axel Jacobi von Wangelin, Michael Seidel, Antje J. Baeumner. Next generation luminol derivative as powerful benchmark probe for chemiluminescence assays. Analytica Chimica Acta 2021, 1188 , 339161. https://doi.org/10.1016/j.aca.2021.339161
  33. Sruthi Prasood Usha, Hariharan Manoharan, Rehan Deshmukh, Ruslan Álvarez-Diduk, Enric Calucho, V. V. R. Sai, Arben Merkoçi. Attomolar analyte sensing techniques (AttoSens): a review on a decade of progress on chemical and biosensing nanoplatforms. Chemical Society Reviews 2021, 50 (23) , 13012-13089. https://doi.org/10.1039/D1CS00137J
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  42. Gaofeng Liang, Haojie Wang, Hao Shi, Haitao Wang, Mengxi Zhu, Aihua Jing, Jinghua Li, Guangda Li. Recent progress in the development of upconversion nanomaterials in bioimaging and disease treatment. Journal of Nanobiotechnology 2020, 18 (1) https://doi.org/10.1186/s12951-020-00713-3
  43. Antonín Hlaváček, Jana Křivánková, Naděžda Pizúrová, Tomáš Václavek, František Foret. Photon-upconversion barcode for monitoring an enzymatic reaction with a fluorescence reporter in droplet microfluidics. The Analyst 2020, 145 (23) , 7718-7723. https://doi.org/10.1039/D0AN01667E
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  45. N. Xin, D. Wei, Y. Zhu, M. Yang, S. Ramakrishna, O. Lee, H. Luo, H. Fan. Upconversion nanomaterials: a platform for biosensing, theranostic and photoregulation. Materials Today Chemistry 2020, 17 , 100329. https://doi.org/10.1016/j.mtchem.2020.100329
  46. Ying Xiong, Yuankui Leng, Xiangmin Li, Xiaolin Huang, Yonghua Xiong. Emerging strategies to enhance the sensitivity of competitive ELISA for detection of chemical contaminants in food samples. TrAC Trends in Analytical Chemistry 2020, 126 , 115861. https://doi.org/10.1016/j.trac.2020.115861
  47. Dongkyu Kang, Eunyoung Jeon, Suyeon Kim, Joonseok Lee. Lanthanide-Doped Upconversion Nanomaterials: Recent Advances and Applications. BioChip Journal 2020, 14 (1) , 124-135. https://doi.org/10.1007/s13206-020-4111-9
  48. Weijie Wu, Mengfei Shen, Xinyi Liu, Lisong Shen, Xing Ke, Wanwan Li. Highly sensitive fluorescence-linked immunosorbent assay based on aggregation-induced emission luminogens incorporated nanobeads. Biosensors and Bioelectronics 2020, 150 , 111912. https://doi.org/10.1016/j.bios.2019.111912
  49. Irshad Mohiuddin, Aman Grover, Jatinder Singh Aulakh, Sang-Soo Lee, Ashok Kumar Malik, Ki-Hyun Kim. Porous molecularly-imprinted polymer for detecting diclofenac in aqueous pharmaceutical compounds. Chemical Engineering Journal 2020, 382 , 123002. https://doi.org/10.1016/j.cej.2019.123002
  50. Mohammad Ramezani, Seyed Mohammad Taghdisi, Rezvan Yazdian-Robati, Fatemeh Oroojalian, Khalil Abnous, Mona Alibolandi. Nanosensors for water safety. 2020, 285-301. https://doi.org/10.1016/B978-0-12-819870-4.00016-5
  51. Xingdong Yang, Yinbiao Wang, Jifei Yang, Zhongke Sun, Cuiwei Chu, Zonghao Yue, Lili Li, Xiaofei Hu. Development of an immunochromatographic lateral flow strip test for the rapid detection of diclofenac in medicinal wine. Food and Agricultural Immunology 2020, 31 (1) , 205-216. https://doi.org/10.1080/09540105.2020.1712331
  52. Pavlína Modlitbová, Antonín Hlaváček, Tereza Švestková, Pavel Pořízka, Lucie Šimoníková, Karel Novotný, Jozef Kaiser. The effects of photon-upconversion nanoparticles on the growth of radish and duckweed: Bioaccumulation, imaging, and spectroscopic studies. Chemosphere 2019, 225 , 723-734. https://doi.org/10.1016/j.chemosphere.2019.03.074
  53. Yejing Jia, Bing Zhang, Honghong Chang, Feiyan Yu, Zhihuan Zhao. TiO2/SnO -Au nanocomposite catalyzed photochromic reaction for colorimetric immunoassay of tumor marker. Journal of Pharmaceutical and Biomedical Analysis 2019, 169 , 75-81. https://doi.org/10.1016/j.jpba.2019.02.040
  54. Veronika Poláchová, Matěj Pastucha, Zuzana Mikušová, Matthias J. Mickert, Antonín Hlaváček, Hans H. Gorris, Petr Skládal, Zdeněk Farka. Click-conjugated photon-upconversion nanoparticles in an immunoassay for honeybee pathogen Melissococcus plutonius. Nanoscale 2019, 11 (17) , 8343-8351. https://doi.org/10.1039/C9NR01246J
  55. Wenbo Yu, Ying Li, Bing Xie, Mingfang Ma, Chaochao Chen, Chenglong Li, Xuezhi Yu, Zhanhui Wang, Kai Wen, Ben Zhong Tang, Jianzhong Shen. An Aggregation-Induced Emission-Based Indirect Competitive Immunoassay for Fluorescence “Turn-On” Detection of Drug Residues in Foodstuffs. Frontiers in Chemistry 2019, 7 https://doi.org/10.3389/fchem.2019.00228
  56. Kewei Wang, Yanli Li, Haijie Li, Mingyuan Yin, Huilin Liu, Qiliang Deng, Shuo Wang. Upconversion fluorescent nanoparticles based-sensor array for discrimination of the same variety red grape wines. RSC Advances 2019, 9 (13) , 7349-7355. https://doi.org/10.1039/C8RA09959F
  57. Diandian Deng, Hong Yang, Chang Liu, Kang Zhao, Jianguo Li, Anping Deng. Ultrasensitive detection of diclofenac in water samples by a novel surface-enhanced Raman scattering (SERS)-based immunochromatographic assay using AgMBA@SiO2-Ab as immunoprobe. Sensors and Actuators B: Chemical 2019, 283 , 563-570. https://doi.org/10.1016/j.snb.2018.12.076
  58. Kexin Wang, Yadan Ding, Xia Hong, Yichun Liu. An infrared IgG immunoassay based on the use of a nanocomposite consisting of silica coated Fe3O4 superparticles. Microchimica Acta 2019, 186 (2) https://doi.org/10.1007/s00604-018-3219-2
  59. Margarita Guenther, Falko Altenkirch, Kai Ostermann, Gerhard Rödel, Ingo Tobehn-Steinhäuser, Steffen Herbst, Stefan Görlandt, Gerald Gerlach. Optical and impedimetric study of genetically modified cells for diclofenac sensing. Journal of Sensors and Sensor Systems 2019, 8 (1) , 215-222. https://doi.org/10.5194/jsss-8-215-2019
  60. Xiaohuan Sun, Ping Liu, Fabrizio Mancin. Sensor arrays made by self-organized nanoreceptors for detection and discrimination of carboxylate drugs. The Analyst 2018, 143 (23) , 5754-5763. https://doi.org/10.1039/C8AN01756E
  61. Stephan Schmidt, Holger Hoffmann, Leif-Alexander Garbe, Rudolf J. Schneider. Liquid chromatography–tandem mass spectrometry detection of diclofenac and related compounds in water samples. Journal of Chromatography A 2018, 1538 , 112-116. https://doi.org/10.1016/j.chroma.2018.01.037
  62. Ming-Kiu Tsang, Yuen-Ting Wong, Jianhua Hao. Upconversion Nanomaterials for Biodetection and Multimodal Bioimaging Using Photoluminescence. 2018, 249-275. https://doi.org/10.1007/978-3-662-56333-5_6
  63. Nadja Steinke, Marisa Rio, Roland Wuchrer, Christiane Schuster, Evgenij Ljasenko, Dietmar Knopp, Gerald Gerlach, Thomas Härtling. Detection of diclofenac molecules by planar and nanostructured plasmonic sensor substrates. Sensors and Actuators B: Chemical 2018, 254 , 749-754. https://doi.org/10.1016/j.snb.2017.07.123
  64. T.T.K. Nguyen, T.T. Vu, G. Anquetin, H.V. Tran, S. Reisberg, V. Noël, G. Mattana, Q.V. Nguyen, Tran Dai Lam, M.C. Pham, B. Piro. Enzyme-less electrochemical displacement heterogeneous immunosensor for diclofenac detection. Biosensors and Bioelectronics 2017, 97 , 246-252. https://doi.org/10.1016/j.bios.2017.06.010
  65. Diego Mendez-Gonzalez, Enrique Lopez-Cabarcos, Jorge Rubio-Retama, Marco Laurenti. Sensors and bioassays powered by upconverting materials. Advances in Colloid and Interface Science 2017, 249 , 66-87. https://doi.org/10.1016/j.cis.2017.06.003
  66. Hans H. Gorris, Ute Resch-Genger. Perspectives and challenges of photon-upconversion nanoparticles - Part II: bioanalytical applications. Analytical and Bioanalytical Chemistry 2017, 409 (25) , 5875-5890. https://doi.org/10.1007/s00216-017-0482-8
  67. Antonín Hlaváček, Miroslav Peterek, Zdeněk Farka, Matthias J. Mickert, Leonhard Prechtl, Dietmar Knopp, Hans H. Gorris. Rapid single-step upconversion-linked immunosorbent assay for diclofenac. Microchimica Acta 2017, 184 (10) , 4159-4165. https://doi.org/10.1007/s00604-017-2456-0
  68. Yiwei Tang, Min Li, Xue Gao, Xiuying Liu, Jinwen Gao, Tao Ma, Jianrong Li. A NIR-responsive up-conversion nanoparticle probe of the NaYF4:Er,Yb type and coated with a molecularly imprinted polymer for fluorometric determination of enrofloxacin. Microchimica Acta 2017, 184 (9) , 3469-3475. https://doi.org/10.1007/s00604-017-2387-9
  69. Bing Zhang, Xue Wang, Yanling Zhao, Jia Lv, Hongyun Meng, Honghong Chang, Hui Zhang, Wenlong Wei. Highly photosensitive colorimetric immunoassay for tumor marker detection based on Cu 2+ doped Ag-AgI nanocomposite. Talanta 2017, 167 , 111-117. https://doi.org/10.1016/j.talanta.2017.02.013
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  • Abstract

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    Figure 1

    Figure 1. Scheme of the indirect competitive ULISA for the detection of diclofenac (DCF). (A) A microtiter plate is coated with a bovine serum albumin-DCF conjugate (BSA-DCF). (B) Dilution series of DCF are prepared in the microtiter plate followed by the addition of anti-DCF mouse antibody. (C) The attachment of anti-DCF antibody is then detected by an anti-mouse IgG-UCNP secondary antibody conjugate. The upconversion luminescence is recorded under 980 nm laser excitation.

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    Figure 2

    Figure 2. Preparation and characterization of IgG-UCNP conjugates. (A) TEM image of silica-coated UCNPs exposing carboxyl groups on the surface (COOH-UCNPs, Supporting Information Figure S3). (B) The carboxyl groups are activated by EDC/sulfo-NHS and conjugated to anti-mouse IgG. (C) The conjugates are prepared by using different ratios of anti-mouse IgG and COOH-UCNPs (I/II, 33 to 1; III/IV, 7 to 1; V/VI, 3 to 1; VII/VIII, no IgG). Each sample is centrifuged either with 4 000g (I, III, V, VII) or with 10 000g (II, IV, VI, VIII) and characterized by agarose gel electrophoresis. The migration distance (Δ) is indicated with red lines. (D) The relative electrophoretic mobility (Δratio[x]/Δno IgG) of the conjugates is linearly dependent on the ratio of IgG molecules per UCNP.

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    Figure 3

    Figure 3. ULISA optimization. (A) Microtiter plates are coated with 1 μg mL–1 of BSA carrying either 10 (red □) or 5.7 (○) DCF residues. (B) The upconversion luminescent (UCL) signal is generated by using 10 μg mL–1 of IgG-UCNP-33:1 (○) or IgG-UCNP-7:1 (red □), respectively. (C) The detection of DCF is optimized by using the monoclonal anti-DCF antibody in concentrations of 0.5 μg mL–1 (○) (IC50, 0.68 ng mL–1), 0.25 μg mL–1 (red □) (IC50, 0.23 ng mL–1), 0.1 μg mL–1 (blue △) (IC50, 0.13 ng mL–1) or 0.02 μg mL–1 (green ◇) (IC50, 0.08 ng mL–1). Error bars represent standard deviations in upconversion signals from three replicate wells.

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    Figure 4

    Figure 4. Normalized calibration curves of ULISA (red □, replotted red curve from Figure 3C; IC50, 0.23 ng mL–1; LOD, 0.05 ng mL–1) and ELISA (○, IC50, 0.05 ng mL–1; LOD, 0.01 ng mL–1). Error bars represent standard deviations of three replicate wells.

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    This article references 37 other publications.

    1. 1
      Wang, L.; Wang, K. M.; Santra, S.; Zhao, X. J.; Hilliard, L. R.; Smith, J. E.; Wu, J. R.; Tan, W. H. Anal. Chem. 2006, 78, 646– 654 DOI: 10.1021/ac0693619
      Google Scholar
      There is no corresponding record for this reference.
    2. 2
      Jans, H.; Huo, Q. Chem. Soc. Rev. 2012, 41, 2849– 2866 DOI: 10.1039/C1CS15280G
      Google Scholar
      There is no corresponding record for this reference.
    3. 3
      Osterfeld, S. J.; Yu, H.; Gaster, R. S.; Caramuta, S.; Xu, L.; Han, S. J.; Hall, D. A.; Wilson, R. J.; Sun, S. H.; White, R. L.; Davis, R. W.; Pourmand, N.; Wang, S. X. Proc. Natl. Acad. Sci. U. S. A. 2008, 105, 20637– 20640 DOI: 10.1073/pnas.0810822105
      Google Scholar
      There is no corresponding record for this reference.
    4. 4
      Čunderlová, V.; Hlaváček, A.; Horňáková, V.; Peterek, M.; Němeček, D.; Hampl, A.; Eyer, L.; Skládal, P. Microchim. Acta 2016, 183, 651– 658 DOI: 10.1007/s00604-015-1697-z
      Google Scholar
      4
      Catalytic nanocrystalline coordination polymers as an efficient peroxidase mimic for labeling and optical immunoassays
      Cunderlova, Veronika; Hlavacek, Antonin; Hornakova, Veronika; Peterek, Miroslav; Nemecek, Daniel; Hampl, Ales; Eyer, Ludek; Skladal, Petr
      Microchimica Acta (2016), 183 (2), 651-658CODEN: MIACAQ; ISSN:0026-3672. (Springer-Verlag GmbH)
      We report that nanocryst. Prussian blue of the type Fe4[Fe(CN)6]3 is a powerful peroxidase mimic for use in labeling of biomols. The cubic nanocrystals typically have a diam. of 15 nm and are capable of catalyzing the oxidn. of colorless 3,3,5,5-tetramethylbenzidine in the presence of H2O2 to form an intensively colored product with an absorption max. at 662 nm. The detd. pseudo turnover no. is ∼20,000 s-1 which is the highest value reported for nanoparticles of a size comparable to common proteins. We also present a method for the biotinylation of the surface of these nanocrystals, and show their use in competitive bioaffinity based assays of biotin and human serum albumin. The limits of detection are 0.35 and 0.27μg mL-1, resp. The results prove the applicability of coordination polymers for signal amplification and also their compatibility with the format of enzyme linked immunosorbent assays.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXitVagtbjN&md5=aba8a56c6dba25e54b186016f1a9fe12
    5. 5
      Hlaváček, A.; Bouchal, P.; Skládal, P. Microchim. Acta 2012, 176, 287– 293 DOI: 10.1007/s00604-011-0729-6
      Google Scholar
      5
      Biotinylation of quantum dots for application in fluoroimmunoassays with biotin-avidin amplification
      Hlavacek, Antonin; Bouchal, Pavel; Skladal, Petr
      Microchimica Acta (2012), 176 (3-4), 287-293CODEN: MIACAQ; ISSN:0026-3672. (SpringerWienNewYork)
      A competitive microplate fluoroimmunoassay was developed for the detn. of human serum albumin in urine. It is based on the use of biotinylated CdTe quantum dots (QDs) whose synthesis is optimized in terms of storage stability, purifn., and signal-to-noise ratio. The bioconjugated QDs were characterised by gel chromatog. and gel electrophoresis. Storage stability and quantum yield were investigated. The excitation/emission wavelengths are 360/620 nm. The immunoassay of human serum albumin in urine has a working range from 1.7 to 10 μg.mL-1, and the limit of detection is 1.0 μg.mL-1.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhsVWktL8%253D&md5=ec11aa982b187d8ce48097a304ea98a2
    6. 6
      Auzel, F. Chem. Rev. 2004, 104, 139– 173 DOI: 10.1021/cr020357g
      Google Scholar
      6
      Upconversion and Anti-Stokes Processes with f and d Ions in Solids
      Auzel, Francois
      Chemical Reviews (Washington, DC, United States) (2004), 104 (1), 139-173CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)
      A review. Topics include: role of energy diffusion in up and down-conversion in energy transfers between rare earth ions; upconversion in a single-ion level description for APTE (i.e., energy transfer upconversion) or excited state absorption (ESA) and in a pair-level one; upconversion studies in lanthanide and actinide ion-doped solids and transition-metal ion-doped solids with APTE and ESA processes; cross-relaxation and the photon avalanche effect; APTE for display and IR detection; APTE and ESA pumped lasers; perspective and future advances in upconversion UV-tunable lasers, in IR imaging, bistability, hot emission and avalanche like codoped systems, and biol. applications.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXovFOhtb4%253D&md5=64dd0339b3dcfa5ef4dc4c7072dc3992
    7. 7
      Haase, M.; Schäfer, H. Angew. Chem., Int. Ed. 2011, 50, 5808– 5829 DOI: 10.1002/anie.201005159
      Google Scholar
      7
      Upconverting Nanoparticles
      Haase, Markus; Schaefer, Helmut
      Angewandte Chemie, International Edition (2011), 50 (26), 5808-5829CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
      A review. Upconversion (UC) refers to nonlinear optical processes in which the sequential absorption of two or more photons leads to the emission of light at shorter wavelength than the excitation wavelength (anti-Stokes type emission). In contrast to other emission processes based on multiphoton absorption, upconversion can be efficiently excited even at low excitation densities. The most efficient UC mechanisms are present in solid-state materials doped with rare-earth ions. The development of nanocrystal research has evoked increasing interest in the development of synthesis routes which allow the synthesis of highly efficient, small UC particles with narrow size distribution able to form transparent solns. in a wide range of solvents. Meanwhile, high-quality UC nanocrystals can be routinely synthesized and their soly., particle size, crystallog. phase, optical properties and shape can be controlled. In recent years, these particles have been discussed as promising alternatives to org. fluorophosphors and quantum dots in the field of medical imaging.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXmvVent74%253D&md5=6ca41c83f4d6c6f3e9193ae6f07c344a
    8. 8
      Ehlert, O.; Thomann, R.; Darbandi, M.; Nann, T. ACS Nano 2008, 2, 120– 124 DOI: 10.1021/nn7002458
      Google Scholar
      There is no corresponding record for this reference.
    9. 9
      Li, X. M.; Zhang, F.; Zhao, D. Y. Chem. Soc. Rev. 2015, 44, 1346– 1378 DOI: 10.1039/C4CS00163J
      Google Scholar
      9
      Lab on upconversion nanoparticles: optical properties and applications engineering via designed nanostructure
      Li, Xiaomin; Zhang, Fan; Zhao, Dongyuan
      Chemical Society Reviews (2015), 44 (6), 1346-1378CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)
      A review. Over the past decade, high-quality lanthanide doped upconverting nanoparticles (UCNPs) have been successfully synthesized with the rapid development of nanotechnol. Due to the unique electron configuration of lanthanide ions, there are rich energy level structures in the near-IR, visible and UV spectral range. However, for UCNPs, only a limited no. of efficient upconversion excitation and emission have been generated due to the limited no. of sensitizer (Yb3+) and activator (Tm3+, Er3+, and Ho3+) ions, and the application is mainly focused on the bio-imaging by using the upconversion luminescence of UCNPs. Recently, more and more researchers have started to focus on tuning of upconversion optical properties and developing of multi-functional UCNPs by using the combination of sub-lattice mediated energy migration, core@shell structural engineering and UCNPs based nanocomposites which greatly expands the range of applications for lanthanide-doped UCNPs. Therefore, a "nanolab" can be created on UCNPs, where the property modulation can be realized via the designed host-dopants combinations, core@shell nanostructure, energy exchange with "alien species" (org. dyes, quantum dots, etc.), and so on. In this paper, we provide a comprehensive survey of the latest advances made in developing lanthanide-doped UCNPs, which include excitation and emission energy levels guided designing of the UCNP nanostructure, the synthesis techniques to fabricate the nanostructure with optimum energy level structure and optical properties, the fabrication of UCNPs-based nanocomposites to extend the applications by introducing the addnl. functional components, or integrating the functional moiety into one nanocomposite.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXht1SlurbJ&md5=33edd049727843cc45b056f366a2931a
    10. 10
      Gorris, H. H.; Ali, R.; Saleh, S. M.; Wolfbeis, O. S. Adv. Mater. 2011, 23, 1652– 1655 DOI: 10.1002/adma.201004697
      Google Scholar
      There is no corresponding record for this reference.
    11. 11
      Päkkilä, H.; Ylihärsilä, M.; Lahtinen, S.; Hattara, L.; Salminen, N.; Arppe, R.; Lastusaari, M.; Saviranta, P.; Soukka, T. Anal. Chem. 2012, 84, 8628– 8634 DOI: 10.1021/ac301719p
      Google Scholar
      There is no corresponding record for this reference.
    12. 12
      Huang, P.; Zheng, W.; Zhou, S. Y.; Tu, D. T.; Chen, Z.; Zhu, H. M.; Li, R. F.; Ma, E.; Huang, M. D.; Chen, X. Y. Angew. Chem., Int. Ed. 2014, 53, 1252– 1257 DOI: 10.1002/anie.201309503
      Google Scholar
      There is no corresponding record for this reference.
    13. 13
      Corstjens, P. L. A. M.; van Lieshout, L.; Zuiderwijk, M.; Kornelis, D.; Tanke, H. J.; Deelder, A. M.; van Dam, G. J. J. Clin. Microbiol. 2008, 46, 171– 176 DOI: 10.1128/JCM.00877-07
      Google Scholar
      13
      Up-converting phosphor technology-based lateral flow assay for detection of Schistosoma Circulating anodic antigen in serum
      Corstjens, Paul L. A. M.; van Lieshout, Lisette; Zuiderwijk, Michael; Kornelis, Dieuwke; Tanke, Hans J.; Deelder, Andre M.; van Dam, Govert J.
      Journal of Clinical Microbiology (2008), 46 (1), 171-176CODEN: JCMIDW; ISSN:0095-1137. (American Society for Microbiology)
      Schistosoma sp. circular anodic antigen (CAA) serum concns. reflect actual worm burden in a patient and are a valuable tool for population screening and epidemiol. research. However, for the diagnosis of individual imported schistosomiasis cases, the current ELISA lacks sensitivity and robustness. Therefore, a lateral flow (LF) assay was developed to test CAA in serum for individual diagnosis of imported active schistosome infections. Application of fluorescent submicron-sized up-converting phosphor technol. (UPT) reporter particles increased anal. sensitivity compared to that of the std. ELISA method. Evaluation of the UPT-LF test with a selection of 40 characterized epidemiol. samples indicated a good correlation between signal intensity and infection intensity. Subsequently, the UPT-LF assay was applied to 166 serum samples of Dutch residents (immigrants and travelers) suspected of schistosomiasis, a case in which group routine antibody detection frequently fails straightforward diagnosis. The UPT-LF assay identified 36 CAA-pos. samples, compared to 15 detected by CAA-ELISA. In conclusion, the UPT-LF assay is a low-complexity test with higher sensitivity than the CAA-ELISA, well suited for lab. diagnosis of individual active Schistosoma infections.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXhs1aqtb0%253D&md5=d94369811b333fb839727192b91b4b05
    14. 14
      Kuningas, K.; Päkkilä, H.; Ukonaho, T.; Rantanen, T.; Lövgren, T.; Soukka, T. Clin. Chem. 2007, 53, 145– 146 DOI: 10.1373/clinchem.2006.076687
      Google Scholar
      14
      Upconversion fluorescence enables homogeneous immunoassay in whole blood
      Kuningas, Katri; Pakkila, Henna; Ukonaho, Telle; Rantanen, Terhi; Lovgren, Timo; Soukka, Tero
      Clinical Chemistry (Washington, DC, United States) (2007), 53 (1), 145-146CODEN: CLCHAU; ISSN:0009-9147. (American Association for Clinical Chemistry)
      A competitive homogeneous immunoassay for 17β-estradiol was employed in whole blood as a model to demonstrate the application of upconversion fluorescence resonance energy transfer (FRET) using a near-IR fluorescent acceptor dye. Because of the relatively transparency of blood to light at wavelengths above 650 nm, the excitation of the up-converting phosphor (UCP) was not attenuated. The measurement of the sensitized acceptor emission above 700 nm completely eliminates the background arising from blood and from possible donor emission, even without temporal resoln. in fluorescence detection. Moreover, in the upconversion FRET-based assay, no emission from the acceptor alone is produced upon IR excitation. The assay is relatively simple and can be performed in a std. microtiter plate assay format using uncomplicated detection instrument.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXmsFGhtA%253D%253D&md5=e098335f71b587b1175f3b25fa1df759
    15. 15
      Arppe, R.; Mattsson, L.; Korpi, K.; Blom, S.; Wang, Q.; Riuttamaki, T.; Soukka, T. Anal. Chem. 2015, 87, 1782– 1788 DOI: 10.1021/ac503691m
      Google Scholar
      There is no corresponding record for this reference.
    16. 16
      Wu, S. J.; Duan, N.; Zhu, C. Q.; Ma, X. Y.; Wang, M.; Wang, Z. P. Biosens. Bioelectron. 2011, 30, 35– 42 DOI: 10.1016/j.bios.2011.08.023
      Google Scholar
      There is no corresponding record for this reference.
    17. 17
      Ternes, T. A. TrAC, Trends Anal. Chem. 2001, 20, 419– 434 DOI: 10.1016/S0165-9936(01)00078-4
      Google Scholar
      There is no corresponding record for this reference.
    18. 18
      Perez, S.; Barcelo, D. TrAC, Trends Anal. Chem. 2007, 26, 494– 514 DOI: 10.1016/j.trac.2007.05.004
      Google Scholar
      There is no corresponding record for this reference.
    19. 19
      Oaks, J. L.; Gilbert, M.; Virani, M. Z.; Watson, R. T.; Meteyer, C. U.; Rideout, B. A.; Shivaprasad, H. L.; Ahmed, S.; Chaudhry, M. J. I.; Arshad, M.; Mahmood, S.; Ali, A.; Khan, A. A. Nature 2004, 427, 630– 633 DOI: 10.1038/nature02317
      Google Scholar
      There is no corresponding record for this reference.
    20. 20
      Koutsouba, V.; Heberer, T.; Fuhrmann, B.; Schmidt-Baumler, K.; Tsipi, D.; Hiskia, A. Chemosphere 2003, 51, 69– 75 DOI: 10.1016/S0045-6535(02)00819-6
      Google Scholar
      There is no corresponding record for this reference.
    21. 21
      Heberer, T. Toxicol. Lett. 2002, 131, 5– 17 DOI: 10.1016/S0378-4274(02)00041-3
      Google Scholar
      21
      Occurrence, fate, and removal of pharmaceutical residues in the aquatic environment: a review of recent research data
      Heberer, Thomas
      Toxicology Letters (2002), 131 (1-2), 5-17CODEN: TOLED5; ISSN:0378-4274. (Elsevier Science Ireland Ltd.)
      A review is given. The occurrence and fate of pharmaceutically active compds. (PhACs) in the aquatic environment has been recognized as one of the emerging issues in environmental chem. In some studies carried out in Austria, Brazil, Canada, Croatia, England, Germany, Greece, Italy, Spain, Switzerland, the Netherlands, and the US, >80 compds., pharmaceuticals and several drug metabolites, have been detected in the aquatic environment. Several PhACs from various prescription classes have been found at concns. up to the μg/L-level in sewage influent and effluent samples and also in several surface waters located downstream from municipal sewage treatment plants (STPs). The studies show that some PhACs originating from human therapy are not eliminated completely in the municipal STPs and are, thus, discharged as contaminants into the receiving waters. Under recharge conditions, polar PhACs such as clofibric acid, carbamazepine, primidone or iodinated contrast agents can leach through the subsoil and have also been detected in several groundwater samples in Germany. Pos. findings of PhACs have, however, also been reported in groundwater contaminated by landfill leachates or manufg. residues. To date, only in a few cases PhACs have also been detected at trace-levels in drinking water samples.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38Xjt1Wju7s%253D&md5=e7d40a736848a1ebfac9df2188a27891
    22. 22
      Sacher, F.; Lange, F. T.; Brauch, H. J.; Blankenhorn, I. J. Chromatogr. A 2001, 938, 199– 210 DOI: 10.1016/S0021-9673(01)01266-3
      Google Scholar
      There is no corresponding record for this reference.
    23. 23
      Petrovic, M.; Hernando, M. D.; Diaz-Cruz, M. S.; Barcelo, D. J. Chromatogr. A 2005, 1067, 1– 14 DOI: 10.1016/j.chroma.2004.10.110
      Google Scholar
      There is no corresponding record for this reference.
    24. 24
      Deng, A. P.; Himmelsbach, M.; Zhu, Q. Z.; Frey, S.; Sengl, M.; Buchberger, W.; Niessner, R.; Knopp, D. Environ. Sci. Technol. 2003, 37, 3422– 3429 DOI: 10.1021/es0341945
      Google Scholar
      There is no corresponding record for this reference.
    25. 25
      Hlaváček, A.; Sedlmeier, A.; Skládal, P.; Gorris, H. H. ACS Appl. Mater. Interfaces 2014, 6, 6930– 6935 DOI: 10.1021/am500732y
      Google Scholar
      There is no corresponding record for this reference.
    26. 26
      Huebner, M.; Weber, E.; Niessner, R.; Boujday, S.; Knopp, D. Anal. Bioanal. Chem. 2015, 407, 8873– 8882 DOI: 10.1007/s00216-015-9048-9
      Google Scholar
      26
      Rapid analysis of diclofenac in freshwater and wastewater by a monoclonal antibody-based highly sensitive ELISA
      Huebner, Maria; Weber, Ekkehard; Niessner, Reinhard; Boujday, Souhir; Knopp, Dietmar
      Analytical and Bioanalytical Chemistry (2015), 407 (29), 8873-8882CODEN: ABCNBP; ISSN:1618-2642. (Springer)
      The non-steroidal anti-inflammatory drug (NSAID) diclofenac (DCF) is found worldwide in the aq. environment. Therefore, it has raised increased public concern on potential long-term impact on human health and wildlife. The importance of DCF has been emphasized by the European Union recently by including this pharmaceutical in the first watch list of priority hazardous substances in order to gather Union-wide monitoring data. Rapid and cheap methods of anal. are therefore required for fresh and wastewater monitoring with high sample load. Here, for the first time, well-characterized monoclonal antibodies (mAbs) against DCF were generated and a highly sensitive ELISA developed. The best antibody (mAb 12G5) is highly affine (KD = 1.5 × 10-10 M), stable to potential matrix interferences such as pH value (pH range 5.2-9.2), calcium ion concn. (up to 75 mg/L), and humic acid content (up to 20 mg/L). The limit of detection (LOD, S/N = 3) and IC50 of the ELISA calibration curve were 7.8 and 44 ng/L, resp. The working range was defined between 11 and 180 ng/L. On av., about 10 % cross-reactivity (CR) was found for DCF metabolites 5-OH-DCF, 4'-OH-DCF, and DCF-acyl glucuronide, but other structurally related NSAIDs showed binding <1 % compared to the parent compd. While DCF concns. at the low ppt range were measured in river and lake water, higher values of 2.9 and 2.1 μg/L were found in wastewater influents and effluents, resp. These results could be confirmed by solid phase extn. combined with LC-MS.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhs1elsLvE&md5=03a86d51982229a7eeef982e2741f4d7
    27. 27
      Wang, F.; Han, Y.; Lim, C. S.; Lu, Y. H.; Wang, J.; Xu, J.; Chen, H. Y.; Zhang, C.; Hong, M. H.; Liu, X. G. Nature 2010, 463, 1061– 1065 DOI: 10.1038/nature08777
      Google Scholar
      There is no corresponding record for this reference.
    28. 28
      Schneider, C. A.; Rasband, W. S.; Eliceiri, K. W. Nat. Methods 2012, 9, 671– 675 DOI: 10.1038/nmeth.2089
      Google Scholar
      28
      NIH Image to ImageJ: 25 years of image analysis
      Schneider, Caroline A.; Rasband, Wayne S.; Eliceiri, Kevin W.
      Nature Methods (2012), 9 (7_part1), 671-675CODEN: NMAEA3; ISSN:1548-7091. (Nature Publishing Group)
      For the past 25 years NIH Image and ImageJ software have been pioneers as open tools for the anal. of scientific images. We discuss the origins, challenges and solns. of these two programs, and how their history can serve to advise and inform other software projects.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtVKntb7P&md5=85ab928cd79f1e2f2351c834c0c600f0
    29. 29
      Sedlmeier, A.; Hlavacek, A.; Birner, L.; Mickert, M. J.; Muhr, V.; Hirsch, T.; Corstjens, P. L.; Tanke, H. J.; Soukka, T.; Gorris, H. H. Anal. Chem. 2016, 88, 1835– 1841 DOI: 10.1021/acs.analchem.5b04147
      Google Scholar
      There is no corresponding record for this reference.
    30. 30
      Liebherr, R. B.; Soukka, T.; Wolfbeis, O. S.; Gorris, H. H. Nanotechnology 2012, 23, 485103 DOI: 10.1088/0957-4484/23/48/485103
      Google Scholar
      There is no corresponding record for this reference.
    31. 31
      Arppe, R.; Hyppänen, I.; Perälä, N.; Peltomaa, R.; Kaiser, M.; Würth, C.; Christ, S.; Resch-Genger, U.; Schäferling, M.; Soukka, T. Nanoscale 2015, 7, 11746– 11757 DOI: 10.1039/C5NR02100F
      Google Scholar
      There is no corresponding record for this reference.
    32. 32
      Wong, Y. J.; Zhu, L.; Teo, W. S.; Tan, Y. W.; Yang, Y.; Wang, C.; Chen, H. J. Am. Chem. Soc. 2011, 133, 11422– 11425 DOI: 10.1021/ja203316q
      Google Scholar
      32
      Revisiting the Stober Method: Inhomogeneity in Silica Shells
      Wong, Yi Jian; Zhu, Liangfang; Teo, Wei Shan; Tan, Yan Wen; Yang, Yanhui; Wang, Chuan; Chen, Hongyu
      Journal of the American Chemical Society (2011), 133 (30), 11422-11425CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
      The SiO2 shell on nanoparticles formed by a typical Stober method is inhomogeneous. The outer layer of the shell is chem. more robust than the inner layer, which can be selectively etched by hot H2O. Methods are developed to harden the soft SiO2 shells. These new understandings are exploited to develop versatile and template-free approaches for fabricating sophisticated yolk-shell nanostructures.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXovVehurY%253D&md5=efdd335fea50aac6298b8c3ca73cbb95
    33. 33
      Bagwe, R. P.; Hilliard, L. R.; Tan, W. H. Langmuir 2006, 22, 4357– 4362 DOI: 10.1021/la052797j
      Google Scholar
      There is no corresponding record for this reference.
    34. 34
      Algar, W. R.; Prasuhn, D. E.; Stewart, M. H.; Jennings, T. L.; Blanco-Canosa, J. B.; Dawson, P. E.; Medintz, I. L. Bioconjugate Chem. 2011, 22, 825– 858 DOI: 10.1021/bc200065z
      Google Scholar
      34
      The Controlled Display of Biomolecules on Nanoparticles: A Challenge Suited to Bioorthogonal Chemistry
      Algar, W. Russ; Prasuhn, Duane E.; Stewart, Michael H.; Jennings, Travis L.; Blanco-Canosa, Juan B.; Dawson, Philip E.; Medintz, Igor L.
      Bioconjugate Chemistry (2011), 22 (5), 825-858CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
      A review. Interest in developing diverse nanoparticle (NP)-biol. composite materials continues to grow almost unabated. This is motivated primarily by the desire to simultaneously exploit the properties of both NP and biol. components in new hybrid devices or materials that can be applied in areas ranging from energy harvesting and nanoscale electronics to biomedical diagnostics. The utility and effectiveness of these composites will be predicated on the ability to assemble these structures with control over NP/biomol. ratio, biomol. orientation, biomol. activity, and the sepn. distance within the NP-bioconjugate architecture. This degree of control will be esp. crit. in creating theranostic NP-bioconjugates that, as a single vector, are capable of multiple functions in vivo, including targeting, image contrast, biosensing, and drug delivery. In this review, a perspective is given on current and developing chemistries that can provide improved control in the prepn. of NP-bioconjugates. The nanoscale properties intrinsic to several prominent NP materials are briefly described to highlight the motivation behind their use. NP materials of interest include quantum dots, carbon nanotubes, viral capsids, liposomes, and NPs composed of gold, lanthanides, silica, polymers, or magnetic materials. This review includes a crit. discussion on the design considerations for NP-bioconjugates and the unique challenges assocd. with chem. at the biol.-nanoscale interface-the liabilities of traditional bioconjugation chemistries being particularly prominent therein. Select bioorthogonal chemistries that can address these challenges are reviewed in detail, and include chemoselective ligations (e.g., hydrazone and Staudinger ligation), cycloaddn. reactions in click chem. (e.g., azide-alkyne cyclyoaddn., tetrazine ligation), metal-affinity coordination (e.g., polyhistidine), enzyme driven modifications (e.g., HaloTag, biotin ligase), and other site-specific chemistries. The benefits and liabilities of particular chemistries are discussed by highlighting relevant NP-bioconjugation examples from the literature. Potential chemistries that have not yet been applied to NPs are also discussed, and an outlook on future developments in this field is given.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXmtVCntb0%253D&md5=df8646d15ead941699bccc3c174fff98
    35. 35
      Sedlmeier, A.; Gorris, H. H. Chem. Soc. Rev. 2015, 44, 1526– 1560 DOI: 10.1039/C4CS00186A
      Google Scholar
      35
      Surface modification and characterization of photon-upconverting nanoparticles for bioanalytical applications
      Sedlmeier, Andreas; Gorris, Hans H.
      Chemical Society Reviews (2015), 44 (6), 1526-1560CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)
      A review. Photon-upconverting nanoparticles (UCNPs) can be excited by near-IR light and emit visible light (anti-Stokes emission) which prevents autofluorescence and light scattering of biol. samples. The potential for background-free imaging has attracted wide interest in UCNPs in recent years. Small and homogeneous lanthanide-doped UCNPs that display high upconversion efficiency have typically been synthesized in org. solvents. Bioanal. applications, however, require a subsequent phase transfer to aq. solns. Hence, the surface properties of UCNPs must be well designed and characterized to grant both a stable aq. colloidal dispersion and the ability to conjugate biomols. and other ligands on the nanoparticle surface. In this review, we introduce various routes for the surface modification of UCNPs and critically discuss their advantages and disadvantages. The last part covers various anal. methods that enable a thorough examn. of the progress and success of the surface functionalization.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsVGjur7K&md5=103ff17432cb75c8fa71ea384111f65e
    36. 36
      Sapsford, K. E.; Tyner, K. M.; Dair, B. J.; Deschamps, J. R.; Medintz, I. L. Anal. Chem. 2011, 83, 4453– 4488 DOI: 10.1021/ac200853a
      Google Scholar
      36
      Analyzing Nanomaterial Bioconjugates: A Review of Current and Emerging Purification and Characterization Techniques
      Sapsford, Kim E.; Tyner, Katherine M.; Dair, Benita J.; Deschamps, Jeffrey R.; Medintz, Igor L.
      Analytical Chemistry (Washington, DC, United States) (2011), 83 (12), 4453-4488CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)
      A review with major sections on purifn., characterization (sepn. techniques, scattering techniques, microscopy, and spectroscopy), modeling, and emerging technologies and instrumentation.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXls1ekt7w%253D&md5=0a45ab29e7a9e9003899247720acd8e5
    37. 37
      Barbarakis, M. S.; Qaisi, W. G.; Daunert, S.; Bachas, L. G. Anal. Chem. 1993, 65, 457– 460 DOI: 10.1021/ac00052a024
      Google Scholar
      There is no corresponding record for this reference.

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    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.analchem.6b01083.

    • Synthesis of UCNPs, calculation of nanoparticle concentrations, TEM and AFM images, DLS and zeta potential measurement, FT-IR spectra, MALDI-TOF analyses, explanation of the hook effect, optimization of the ULISA, and characterization of water samples (PDF)


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