Applications of Aptasensing Paper-Based Analytical Devices

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1		Anastasios Economou	--	3804	2023-09-13 11:36:35	\|
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This entry is adapted from the peer-reviewed paper 10.3390/s23187786

Aptamers are short oligonucleotides designed to possess high binding affinity towards specific target compounds (ions, molecules, or cells). Due to their function and unique advantages, aptamers are considered viable alternatives to antibodies as biorecognition elements in bioassays and biosensors. On the other hand, paper-based devices (PADs) have emerged as a promising and powerful technology for the fabrication of low-cost analytical tools, mainly intended for on-site and point-of-care applications.

aptasensors aptamers paper-based devices

1. Ions

Paper-based aptasensors have been mainly reported for the quantification of metal ions, many of them of environmental importance due to their toxicity (e.g., Pb(II), Hg(II)) or biological function (e.g., K⁺). The common methods for the determination of these cations are based on advanced spectroscopic techniques that offer low limits of detection and multi-metal determinations ^[1]. However, these methodologies are laboratory-based, requiring expensive and bulky equipment, trained personnel, and sample pretreatment. In contrast, aptasensing PADs can serve as sensitive, low-cost on-site diagnostic devices to acquire preliminary information on potential heavy metal contamination in many samples ^[2]. However, the selection of aptamer sequences for heavy metals is challenging, and in many cases the binding selectivity is low ^[2], while other competing low-cost and field-deployable analytical approaches are available (e.g., stripping voltammetry ^[3]).

A paper-based calorimetric aptasensor has been fabricated for K⁺ detection using cationic dyes ^[4]. The cationic dye (Y5GL) serves as an aggregator, which changes the AuNP solution color from blue-purple to green. In the presence of K⁺, the aptamer dissociates from the surface of the AuNPs, so that the free AuNPs and cationic dye make the solution green. The linear range of the aptasensor was from 10 μM to 40 mM and the limit of detection (LOD) of 6.2 μM was obtained.

Another aptasensing microfluidic PAD has been reported for Pb²⁺ ions in the water ^[5]. It is based on the aggregation of AuNPs with NaCl, leading to a color change from red to purple in the presence of Pb²⁺. Whatman No. 1 and nylon filter papers were used as the platform of this assay with a linear range from 10 nM to 1 mM for both supports; the LODs were 1.2 nm and 0.7 nm, respectively.

An aptasensing PAD, based on FRET, was proposed for the detection of Pb²⁺ ^[6]. The detection exploits conformational transformations of the Pb²⁺-specific aptamer that affect its binding with GO. The addition of the target Pb²⁺ induces the release of the specific aptamer from the GO surface, thus restoring the fluorescence emission. The linearity held in the ranges 5–70 pM and 0.07–20 nM with an LOD of 0.5 pM.

Finally, a CL cellulose aptasensor was introduced for Hg²⁺ detection in water using a sandwich assay made up of two aptamers ^[7]. A capture aptamer (S1) is immobilized on paper. When the target Hg²⁺ is captured by S1, it is tagged by the second aptamer (S2), which is modified with CL reagents (phenylene-ethynylene reagents on nanoporous silver). Finally, CL is induced via the addition of permanganate. This device allowed Hg²⁺ detection in a range of 20 nM to 0.5 μM with an LOD of 1 pM.

2. Small Molecules

Small molecules are typically organic compounds with a molecular weight of <900–1000 Daltons and comprise a large variety of natural or man-made compounds of environmental, biological, pharmaceutical, or industrial importance. Natural food contaminants (such as toxic mycotoxins, aflatoxins, and ochratoxins produced by fungi), pesticides, many pharmaceuticals (e.g., antibiotics), and human body regulators (such as vitamins and hormones) are typical examples of small molecules with high significance. The main challenges in the development of aptasensors for small molecules are related to the structure of the targets, the aptamer selection process, and the determination of the binding constant ^[8]. The small size of the target and the lack of functional groups available for immobilization or interaction with nucleic acids make the selection process of small molecules’ aptamers very challenging. Nevertheless, the current progress in SELEX technologies such as high-throughput sequencing (HTS) and post-SELEX optimization procedures has led to improved screening of aptamers that are selective to small molecules ^[9]^[10]. However, aptamers provide appropriate binding pockets within their tertiary structures for the recognition of small molecules and are, therefore, better small-molecule receptors compared to antibodies ^[11].

Saraf et al. proposed a simple label-free colorimetric aptasensor for epinephrine detection ^[12]. The detection of epinephrine is based on the interaction with aptamer-functionalized AuNPs. A change in color from red to blue was observed in the solution with increasing concentrations of epinephrine, and the LOD was 0.9 nM.

In another work, a fluorescent paper-based aptasensing method was developed for simultaneous aminoglycoside detection (streptomycin, tobramycin, and kanamycin) ^[13]. The paper platform consists of five paper layers and four parallel channels. Aptamer/graphitic carbon nitride nanosheet-modified layers can catalyze o-phenylenediamine to fluorescent 2,3-diaminophenazine (DAP) in the presence of H₂O₂. The peroxidase-like activity is reduced when the aptamer is detached from the nanosheets as a result of its binding with the target molecules. The calibration curves for streptomycin, tobramycin, and kanamycin were linear in the ranges 0.01–30 ng mL⁻¹, 0.1–150 ng mL⁻¹, and 0.05–150 ng mL⁻¹, respectively, and the LODs were estimated as 0.023, 0.069, and 0.045 ng mL⁻¹, respectively.

Martínez-Jarquín et al. introduced a paper platform (called “aptapaper”) modified with aptamers for the separation, preconcentration, and semi-quantitation of quinine and serotonin ^[14]. After preconcentration of the targets on the aptapaper, they were detected by paper spray ionization coupled with high-resolution mass spectrometry. The LODs were 81 pg mL⁻¹ and 1.8 ng mL⁻¹ for quinine and serotonin, respectively.

A portable paper-based sensor system has been reported for the rapid detection of tetracycline and guanosine tetraphosphate ^[15]. The target detection is performed on RNA-modified filter papers using a target-binding aptamer with fluorogenic RNA. The binding of the target with the aptamer induced the folding of the RNA, which activated the fluorescence of a fluorophore (DFHBI-1T). This sensor was used for the selective determination of tetracycline with a linear range of 0.1–0.8 mM and of guanosine tetraphosphate in the range of 0.1–10 μM.

In addition, a potentiometric aptasensor using a graphene paper support was proposed to detect kanamycin ^[16]. A nuclease-assisted amplification process was implemented in order to significantly improve the detection sensitivity via the catalytic recycling reaction of the target induced by the nuclease (DNase I). This aptasensor exhibits linear ranges in the 0.03–20 pg mL⁻¹ and 20–150 pg mL⁻¹ intervals with an LOD of 30.0 fg mL⁻¹.

A self-powered origami PAD was implemented by Liu et al. to determine adenosine ^[17]. The device uses an aptamer to recognize an analyte, GOx to modify the relative concentrations of the [Fe(CN)₆]³⁻/[Fe(CN)₆]⁴⁻ redox couple, and a digital multimeter to record the result of the assay. This device offers an LOD for adenosine of 11.8 μM.

A flower-shaped microfluidic paper biosensor for gentamicin in milk ^[18] was developed employing colorimetric detection of the salt-induced aggregation of AuNPs with an LOD of 300 nM.

Ming et al. described a folding, label-free electrochemical aptasensor to detect estradiol ^[19]. Amine-functionalized single-walled carbon nanotube/methylene blue/AuNPs were immobilized on the working electrode to increase its detection sensitivity and immobilize the aptamer. The principle is based on a decrease in the voltametric response as soon as the aptamer and target combine. A linear range of 0.01–500 ng mL⁻¹ and an LOD of 5 pg mL⁻¹ were achieved.

Zhang et al. have fabricated an electrochemical aptasensor to detect ochratoxin A ^[20]. The complementary aptamer was attached to a MXene-Au electrode decorated with Pt nanoparticles (NPs) anchored in hollow structures of NiCo-layered double hydroxides as signal amplification materials via Au-S bonds. Then, aptamer (apta)-binding Pt@NiCo-LDH with peroxidase-like activity was immobilized through hybridization to trigger the “signal on” state, generating a significant electrochemical signal. The presence of ochratoxin A enabled the dissociation of the aptamer-complimentary aptamer hybrid, releasing signal amplification labels to achieve a “signal off” state. The aptasensor exhibited a linear range from 20 fg mL⁻¹ to 100 ng mL⁻¹ and an LOD of 8.9 fg mL⁻¹.

An origami ECL aptasensor was developed for adenosine triphosphate using an AuNPs-modified paper-working electrode ^[21]. The sandwich assay employs a thiolated capture aptamer that is immobilized on the working electrode and an amino-modified probe aptamer with ECL Pt–Ag alloy nanoparticle labels. The presence of the target induces hybridization of the two fragments, leading to enhancement of the ECL intensity. The LOD was 0.1 pmol L⁻¹, and the linear range was from 0.5 pmol L⁻¹ to 7.0 nmol L⁻¹.

Finally, an aptamer was used as a molecular recognition element coupled with the target-induced color change of AuNPs for colorimetric detection of ochratoxin A in a microfluidic paper-based analytical device ^[22]. Although the device can only provide a Yes/No qualitative result, it has the potential to rapidly detect ochratoxin A without pre-treatment steps.

3. Large Molecules and Proteins

The field of protein detection on PADs is dominated by immunosensors, which utilize antibodies as the biorecognition element ^[23]. Antibodies are considered the “gold standard” since their high affinity and specificity to bind their target analyte have naturally evolved over long periods of time, and, in addition, there has been accumulated expertise on their use for biosensor design for many decades ^[24]. Recent studies comparing the relative performance of aptamers and antibodies in biosensor design (in terms of selectivity and sensitivity) are inconclusive because the results depend strongly on many experimental variables, the most important being the proper integration of the biosensing element with the transducer ^[25].

A syringe-based colorimetric paper aptasensor has been reported for the assay of the malaria biomarker Plasmodium falciparum lactate dehydrogenase ^[26]. The target protein is captured by the aptamer immobilized on microbeads and is detected by a color change due to its enzymatic activity upon a development reagent. The device responds to concentrations of the biomarker spanning four orders of magnitude and achieves an LOD of 5 ng mL⁻¹.

In another interesting work, aptamers were selected to discriminate B. caeruleus (common krait) venom from cobra, Russell’s, and saw-scaled viper’s venom ^[27]. The selected aptamers (against the β-bungarotoxin present in the specific venom) were used as a molecular recognition element in a colorimetric paper-based devicethat was able to detect 2 ng krait venom.

A novel cellulose-based aptasensor for the colorimetric detection of the cancer biomarker protein osteopontin has been reported ^[28]. The paper was chemically modified with (mercaptopropyl)methyldimetoxisilane to attach the thiolated aptamer. Colorimetric detection was performed using a Bradford reagent. The linear range was 5–1000 ng mL⁻¹ and the LOD was <5 ng mL⁻¹.

In addition, Li et al. have reported on a colorimetric aptamer-based assay for the detection of platelet-derived growth factor, a target protein on bioactive paper ^[29]. The aptamer was self-assembled onto graphene oxide, followed by desorption induced by the specific binding of the target. The released aptamer hybridizes to paper-bound DNA primers, thus initiating a rolling circle amplification reaction to produce a long DNA molecule containing multiple horseradish peroxidase-mimicking DNAzyme moieties that catalyze the oxidation of substrates by H₂O₂ in the presence of hemin. This device can achieve detection of the target protein at 100 pmol L⁻¹ with a linear range from 0.001 to 10 nmol L⁻¹.

A microfluidic paper-assisted analytical device was developed to determine the food allergens arachin, β-lactoglobulin, and tropomyosin using a colorimetric assay ^[30]. AuNPs were conjugated with biotinylated aptamers and incubated with the sample. In the absence of analytes, the AuNP-aptamer conjugates will not adsorb on GO, but in the presence of analytes, the AuNP-aptamer conjugates will adsorb on GO-forming aggregates. Allergens were determined in the 25–1000 nmol L⁻¹ range with LODs ranging from 6.2 to 12.4 nmol L⁻¹.

A paper-based aptasensor with FRET detection has been proposed for the detection of the malaria biomarker Plasmodium lactate dehydrogenase ^[31]. Fluorescently labeled aptamers towards the target protein were incubated with fluorescence-quenching MoS₂ nanosheets that reduced the fluorescence of the aptamers. If the sample contains the target, this will bind to the aptamers and restore the fluorescence.

Ma et al. have developed an electrochemiluminescence (ECL) aptasensor for the peptide mucin-1, which is an important cancer marker ^[32]. The detection is based on the release of a strand from a target-specific aptamer in the presence of the peptide. This strand triggers a hybridization chain reaction between two hairpin probes, which is detected via an ECL probe (Ru(phen)₃²⁺). The device enables the detection of mucin-1 in the range of 25–50 nM with an LOD of 8.33 pM.

Another paper-based bipolar ECL aptasensor for carcinoembryonic antigen has been reported ^[33]. An aptamer immobilized on paper is used to capture the antigen. A conjugate of a second aptamer with gold-coated Fe₃O₄ nanoparticles is captured by the antigen and attached to the cathode of a bipolar cell, catalyzing the reduction of H₂O₂ and enhancing the ECL emission at the anode. This aptasensor allows detection in a range of 0.1–15 ng mL⁻¹ with an LOD of 0.03 pg mL⁻¹.

A FRET protocol was adopted to develop a paper-based aptasensor for immunoglobulin E ^[34]. Luminescent upconversion nanoparticles serve as energy donors and carbon nanoparticles as energy acceptors to quench the fluorescence. Upon exposure to immunoglobulin E, the luminescence is recovered. The aptasensor allows the determination of the target in the range of 0.5–80 ng mL⁻¹.

An electrochemical aptasensor was proposed to detect hemoglobin A1c ^[35]. A nanocomposite of reduced graphene oxide and gold was electrochemically deposited on graphite paper and used to immobilize an aptamer. In the presence of the target the DPV current of the Fe(CN)₆³⁻/Fe(CN)₆⁴⁻ probe was reduced. The linear range was 1 nmol L⁻¹–13.83 μmol L⁻¹ and the LOD was 1 nmol L⁻¹.

Wei et al. have proposed a microfluidic electrochemical aptasensor for prostate specific antigen (PSA) detection ^[36]. AuNPs/reduced graphene oxide (rGO)/thionine composites were coated onto the working electrode for the immobilization of the aptamer probe. Thionine serves as an electrochemical mediator of the recognition event between the aptamer and the target. The LOD was 10 pg mL⁻¹, and the linear range was 0.05 to 200 ng mL⁻¹.

An electrochemical sensing platform has been reported that can detect carcinoembryonic antigen and other biomarkers ^[37]. A hairpin probe (containing the specific aptamer sequence) binds to the target and the binding event induces a conformational change of the probe exposing its occluded stem region. The exposed domain triggered a polymerization reaction generating DNAzyme strands that produce an amplified signal response.

A paper-based electrochemical aptasensor for carcinoembryonic antigen has been fabricated ^[38]. A graphene/poly (3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS)-modified paper serves as the conductive substrate for the aptamer immobilization. The target binding is followed by EIS with a linear range 0.77–14 ng mL⁻¹ and an LOD of 1.06 ng mL⁻¹ in serum.

A photoelectrochemical cellulose-based aptasensing platform was proposed to detect thrombin by Xue et al. using a dual electron-transfer tunneling distance regulation (ETTDR) and aptamer target-triggering nicking enzyme signaling amplification (NESA) strategy ^[39]. In the presence of TB, a large number of secondary tDNA pieces are generated and hybridized with CeO₂-labeled hairpin DNA immobilized on the electrode surface causing an amplified photocurrent to decrease. The aptasensor has linear range of 0.02–100 p mol L⁻¹ with an LOD of 6.7 fmol L⁻¹.

Another photoelectrochemical aptasensor was proposed for prostate-specific antigen based on TiO₂/black phosphorus quantum dots (TiO₂–BPQDs) was proposed for PSA detection ^[40]. Carbon nanotubes, TiO₂, black phosphorus quantum dots, and capture DNA were sequentially immobilized on paper to bind AuNPs-modified aptamer. Upon adding the target, the aptamer dissociates from the electrode leading to photocurrent amplification. The linear range is 0.005–50 ng mL⁻¹ and the LOD is 1 pg mL⁻¹.

Azuaje-Hualde et al. have developed a cellulose microfluidic paper-based analytical device for the detection of Vascular Endothelial Growth Factor (VEGF) ^[41]. A three-part aptamer structure was designed with an aptameric sequence specific for the target which hybridizes with a fluorescent strand and a quencher strand. The presence of the target triggers the displacement of a quencher strand and increase in the fluorescence intensity. The LOD was 137 ng mL⁻¹ and the linear range was 0.1–5 mg mL⁻¹.

An origami electrochemical paper-based aptasensor was fabricated for label-free detection of epidermal growth factor receptors ^[42]. Amino-functionalized graphene/thionine/AuNPs nanocomposites were used to modify the working electrode and facilitate the immobilization of specific thiol-modified aptamers. The principle of detection was the inhibition of the electron transfer rate with the formation of the aptamer–antigen bioconjugates. The biosensors enabled detection at 5 pg mL⁻¹ and a linear range of 0.05–200 ng mL⁻¹.

4. Cells and Bacteria

The targets of aptamers for the detection of cells can be specific proteins or receptors at the surface of the cells, bacterial virulence factors or even the very cells themselves, and the SELEX selection process should be tailored according to the target selection ^[43].

Two similar paper-based ECL aptasensors were developed to detect cancer cells ^[44]^[45]. Aptamers are immobilized on the AuNPs-modified electrode via Au-S bonds and capture the target cells. Concanavalin A-labeled AuPd alloy nanoparticles bind to the captured cells amplifying the ECL signal. The devices can perform detection in the range of ~450–1.0 × 10⁷ cells mL⁻¹ with an LOD of ~250 cells mL⁻¹.

The same group has reported a paper-based voltammetric sandwich assay to detect human acute promyelocytic leukemia cells ^[46]. The Au-paper electrode is modified with aptamers to capture the cancer cells and horseradish peroxidase-labeled folic acid binds to the captured cells (via recognition of folic by folate receptors on the cell surface) which catalyzes the oxidation of o-phenylenediamine by H₂O₂; the enzymatic product is monitored by differential pulse voltammetry. The device enables detection in a range of 5.0 × 10²–7.5 × 10⁷ cells mL⁻¹ with an LOD of 350 cells mL⁻¹.

A novel aptasensor based on an electrochemical paper-based analytical device has been proposed for the detection of Listeria monocytogenes ^[47]. The paper substrate was modified with a tungsten disulfide/aptamer hybrid and detection was performed with EIS using methylene blue as a probe. A LOD of 4.5 CFU mL⁻¹ and a range of 10–10⁸ CFU mL⁻¹ were obtained.

A paper-based potentiometric sensor was fabricated to detect the Zika virus with an LOD of 2.4 × 10⁷ ^[48]. The sensor consists of 2 segments of paper (sample and reference segments) with conducting silver paint contact patches on two ends and impregnated with aptamers against Zika. When the virus is added to the sample region, a Nernstian potential difference is generated between the sample and reference regions.

Wang et al. have reported on a paper-based dual-mode cyto-aptasensor for simultaneous electrochemical and colorimetric detection of breast cancer MCF-7 cells ^[49]. The on-paper working electrode is modified with reduced graphene oxide (rGO) and AuNPs to bind a first aptamer and capture the target cells. AuPd alloy nanoparticle detection probes combine with a second aptamer and are immobilized on the captured MCF-7 cells. The probes catalyze the oxidation of H₂O₂ resulting in an amplified electrochemical signal. In addition, the generated •OH can also produce a colorimetric signal. This device enables a linear detection range of 50–10⁷ cells mL⁻¹ with an LOD of 20 cells mL⁻¹.

Another dual-mode aptasensor was developed for MCF-7 and K562 cells by Li et al. ^[50]. The paper-based device was fabricated in six layers. For electrochemical detection, an Au-modified working electrode was used to bind a target-specific aptamer. The complementary DNA strand, labeled with methylene blue (MB), is hybridized on the electrode and is released in the presence of target cells. Aptamer-labeled Pd–Pt nanoparticles that are loaded with ferrocene (Fc) are linked onto electrode, resulting in an increased Fc/MB current intensity ratio. For colorimetric detection, H₂O₂ is added to the paper and, in the presence of the target cells, more aptamer-labeled Pd–Pt nanoparticles are linked to the electrode, resulting in increased consumption of H₂O₂ and decreased consumption of the sealing reagent (AgNPs). The cell concentration can be calculated based on the distance that the liquid moves. This aptasensor enables detection of MCF-7 and K562 cells in ranges of 150–1.0 × 10⁷ and 220–7.0 × 10⁶ cells mL⁻¹ with LODs of 117 and 140 cells mL⁻¹, respectively.

5. Multiplexed Assays

Multiplexed assays for the simultaneous detection of more than one analyte are extremely important. A prominent example is clinical analysis, in which several biomarkers are often necessary to monitor specific diseases (such as cancer, cardiovascular disorders, or diabetes). Another typical example is food safety since it is desirable to monitor many toxic compounds that can potentially co-exist in foodstuffs (such as mycotoxins, antibiotics, and bacteria). Apart from their higher diagnostic potential, such multi-analyte assays provide lower cost per test and higher throughput than single-analyte assays. Different multiplexed aptasensing strategies have been reported so far ^[51].

A low-cost paper-based aptasensor was developed featuring two test zones to simultaneously monitor Hg²⁺ and Ag⁺ using a FRET approach ^[52]. The linear ranges were 0.05–50 nM for both Hg²⁺ and Ag⁺ while the LODs for Hg²⁺ and Ag⁺ were 1.33 and 1.01 pM, respectively.

A paper-based microfluidic chip was developed in order to detect food allergens and food toxins (lysozyme, ß-conglutin, lupine, okadaic acid, and brevetoxin) simultaneously ^[53]. The targets were bound onto aptamer-functionalized quantum dots (QDs). After mixing with the GO, the fluorescence was quenched via the FRET process while the presence of target proteins restored the fluorescence intensity. The LODs ranged from 0.56 ng mL⁻¹ to 343 ng mL⁻¹, depending on the analyte.

A duplex electrochemical aptasensor to detect simultaneously carcinoembryonic antigen and neuron-specific enolase has been reported ^[54]. The device makes use of a stacked microfluidic configuration. The working electrodes were modified with amino functional graphene/thionine/AuNPs and Prussian blue/poly (3, 4-ethylenedioxythiophene)/AuNPs nanocomposites to improve the electron transfer rate and immobilization efficiency of the aptamers. The aptasensor enables detection of carcinoembryonic antigen and neuron-specific enolase in ranges of 0.01–500 ng mL⁻¹ and 0.05–500 ng mL⁻¹, with LODs of 2 pg mL⁻¹ and 10 pg mL⁻¹, respectively.

An electrochemical lab-on-paper cyto-device was fabricated for specific cancer cell detection and in-situ monitoring of multi-glycans on cancer cells ^[55]. An aptamer-modified AuNPs-paper electrode was employed as the working electrode for cancer cell capture. Horseradish peroxidase-labeled with wheat germ agglutinin, peanut agglutinin, concanavalin A and with dolichos biflorus agglutinin were used as probes for the four glycans in a sandwich format. The device could detect the target cells in the range 550 to 2.0 × 10⁷ cells mL⁻¹ and was applied to in-situ monitor cell-surface multi-glycans in parallel.

A paper-based microfluidic for duplex colorimetric detection of E. coli O157:H7 and S. Typhimurium has been fabricated ^[56]. Polystyrene microparticles decorated with AuNPs were used as colorimetric labels for salt-based aggregation. Linearity held for 10² CFU mL⁻¹ to 10⁸ CFU mL⁻¹ and the LODS were of 10³ CFU mL⁻¹ and 10² CFU mL⁻¹ for E. coli O157:H7 and S. Typhimurium, respectively.

Liang et al. have developed a paper-based FRET aptasensing device for multiplexed monitoring of three kinds of cancer cells (MCF-7, HL-60, and K562) ^[57]. Quantum dots-coated silica nanoparticles are labeled with aptamers which are adsorbed on the surface of GO causing decrease in fluorescence; upon addition of the target cells, the fluorescence intensity is recovered. The linear ranges were from 180 to 8 × 10⁷, 210 to 7 × 10⁷, 200 to 7 × 10⁷ cells mL⁻¹, and the LODs were 6270 and 65 cells mL⁻¹ for MCF-7, HL-60, and K562 cells, respectively.

A microfluidic paper-based manifold has been designed for the multiplexed detection of three types of bacteria (Acinetobacter baumannii, Escherichia coli, and Staphylococcus aureus) ^[58]. Specific aptamers were immobilized on the nitrocellulose support and were used to capture the bacteria. Secondary biotin-labeled aptamers were incubated with the captured target bacteria, streptavidin-conjugated HRP was added and, finally, tetramethyl benzidine (TMB) reagent was used as a colorimetric probe. The LOD was ~10³ CFU μL⁻¹ and the linear range ranged from 10² to 10⁵ CFU μL⁻¹.

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Anastasios Economou

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Update Date: 14 Sep 2023

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