Integrating high-performing electrochemical transducers in lateral flow assay

Analytical and Bioanalytical Chemistry ◽

10.1007/s00216-021-03301-y ◽

2021 ◽

Author(s):

Antonia Perju ◽

Nongnoot Wongkaew

Keyword(s):

High Performance ◽

Point Of Care ◽

Low Cost ◽

High Sensitivity ◽

Lateral Flow ◽

Analytical Performance ◽

Label Free ◽

High Performing ◽

Lateral Flow Assays ◽

Electrochemical Transducers

AbstractLateral flow assays (LFAs) are the best-performing and best-known point-of-care tests worldwide. Over the last decade, they have experienced an increasing interest by researchers towards improving their analytical performance while maintaining their robust assay platform. Commercially, visual and optical detection strategies dominate, but it is especially the research on integrating electrochemical (EC) approaches that may have a chance to significantly improve an LFA’s performance that is needed in order to detect analytes reliably at lower concentrations than currently possible. In fact, EC-LFAs offer advantages in terms of quantitative determination, low-cost, high sensitivity, and even simple, label-free strategies. Here, the various configurations of EC-LFAs published are summarized and critically evaluated. In short, most of them rely on applying conventional transducers, e.g., screen-printed electrode, to ensure reliability of the assay, and additional advances are afforded by the beneficial features of nanomaterials. It is predicted that these will be further implemented in EC-LFAs as high-performance transducers. Considering the low cost of point-of-care devices, it becomes even more important to also identify strategies that efficiently integrate nanomaterials into EC-LFAs in a high-throughput manner while maintaining their favorable analytical performance.

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PCB-Based Magnetometer as a Platform for Quantification of Lateral-Flow Assays

Sensors ◽

10.3390/s19245433 ◽

2019 ◽

Vol 19 (24) ◽

pp. 5433 ◽

Cited By ~ 3

Author(s):

Mohammad Khodadadi ◽

Long Chang ◽

João R. C. Trabuco ◽

Binh V. Vu ◽

Katerina Kourentzi ◽

...

Keyword(s):

High Precision ◽

Fe3o4 Nanoparticles ◽

Printed Circuit Board ◽

Test Line ◽

Point Of Care ◽

Low Cost ◽

Superparamagnetic Iron Oxide ◽

High Sensitivity ◽

Lateral Flow ◽

Circuit Board

This work presents a proof-of-concept demonstration of a novel inductive transducer, the femtoMag, that can be integrated with a lateral-flow assay (LFA) to provide detection and quantification of molecular biomarkers. The femtoMag transducer is manufactured using a low-cost printed circuit board (PCB) technology and can be controlled by relatively inexpensive electronics. It allows rapid high-precision quantification of the number (or amount) of superparamagnetic nanoparticle reporters along the length of an LFA test strip. It has a detection limit of 10−10 emu, which is equivalent to detecting 4 ng of superparamagnetic iron oxide (Fe3O4) nanoparticles. The femtoMag was used to quantify the hCG pregnancy hormone by quantifying the number of 200 nm magnetic reporters (superparamagnetic Fe3O4 nanoparticles embedded into a polymer matrix) immuno-captured within the test line of the LFA strip. A sensitivity of 100 pg/mL has been demonstrated. Upon further design and control electronics improvements, the sensitivity is projected to be better than 10 pg/mL. Analysis suggests that an average of 109 hCG molecules are needed to specifically bind 107 nanoparticles in the test line. The ratio of the number of hCG molecules in the sample to the number of reporters in the test line increases monotonically from 20 to 500 as the hCG concentration increases from 0.1 ng/mL to 10 ng/mL. The low-cost easy-to-use femtoMag platform offers high-sensitivity/high-precision target analyte quantification and promises to bring state-of-the-art medical diagnostic tests to the point of care.

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Portable tumor biosensing of serum by plasmonic biochips in combination with nanoimprint and microfluidics

Nanophotonics ◽

10.1515/nanoph-2018-0173 ◽

2019 ◽

Vol 8 (2) ◽

pp. 307-316 ◽

Cited By ~ 17

Author(s):

Jianyang Zhou ◽

Feng Tao ◽

Jinfeng Zhu ◽

Shaowei Lin ◽

Zhengying Wang ◽

...

Keyword(s):

Nanoimprint Lithography ◽

Clinical Medicine ◽

Point Of Care ◽

Low Cost ◽

Human Tumor ◽

High Sensitivity ◽

Visible Range ◽

Label Free ◽

Portable Detection ◽

Clinical Experiments

AbstractPlasmonic sensing has a great potential in the portable detection of human tumor markers, among which the carcinoembryonic antigen (CEA) is one of the most widely used in clinical medicine. Traditional plasmonic and non-plasmonic methods for CEA biosensing are still not suitable for the fast developing era of Internet of things. In this study, we build up a cost-effective plasmonic immunochip platform for rapid portable detection of CEA by combining soft nanoimprint lithography, microfluidics, antibody functionalization, and mobile fiber spectrometry. The plasmonic gold nanocave array enables stable surface functionality, high sensitivity, and simple reflective measuring configuration in the visible range. The rapid quantitative CEA sensing is implemented by a label-free scheme, and the detection capability for the concentration of less than 5 ng/ml is achieved in clinical experiments, which is much lower than the CEA cancer diagnosis threshold of 20 ng/ml and absolutely sufficient for medical applications. Clinical tests of the chip on detecting human serums demonstrate good agreement with conventional medical examinations and great advantages on simultaneous multichannel detections for high-throughput and multi-marker biosensing. Our platform provides promising opportunities on low-cost and compact medical devices and systems with rapid and sensitive tumor detection for point-of-care diagnosis and mobile healthcare.

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Electrospun Polycaprolactone Nanofibers as a Reaction Membrane for Lateral Flow Assay

Polymers ◽

10.3390/polym10121387 ◽

2018 ◽

Vol 10 (12) ◽

pp. 1387 ◽

Cited By ~ 13

Author(s):

Chee Yew ◽

Pedram Azari ◽

Jane Choi ◽

Farina Muhamad ◽

Belinda Pingguan-Murphy

Keyword(s):

Flow Rate ◽

Point Of Care ◽

Low Cost ◽

Average Pore Size ◽

Lateral Flow ◽

Detection Sensitivity ◽

Average Pore ◽

Water Contact ◽

Naoh Solution ◽

Lateral Flow Assays

Electrospun polycaprolactone (PCL) nanofibers have emerged as a promising material in diverse biomedical applications due to their various favorable features. However, their application in the field of biosensors such as point-of-care lateral flow assays (LFA) has not been investigated. The present study demonstrates the use of electrospun PCL nanofibers as a reaction membrane for LFA. Electrospun PCL nanofibers were treated with NaOH solution for different concentrations and durations to achieve a desirable flow rate and optimum detection sensitivity in nucleic acid-based LFA. It was observed that the concentration of NaOH does not affect the physical properties of nanofibers, including average fiber diameter, average pore size and porosity. However, interestingly, a significant reduction of the water contact angle was observed due to the generation of hydroxyl and carboxyl groups on the nanofibers, which increased their hydrophilicity. The optimally treated nanofibers were able to detect synthetic Zika viral DNA (as a model analyte) sensitively with a detection limit of 0.5 nM. Collectively, the benefits such as low-cost of fabrication, ease of modification, porous nanofibrous structures and tunability of flow rate make PCL nanofibers a versatile alternative to nitrocellulose membrane in LFA applications. This material offers tremendous potential for a broad range of point-of-care applications.

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Engineering luminescent biosensors for point-of-care SARS-CoV-2 antibody detection

10.1101/2020.08.17.20176925 ◽

2020 ◽

Author(s):

Susanna K. Elledge ◽

Xin X. Zhou ◽

James R. Byrnes ◽

Alexander J. Martinko ◽

Irene Lui ◽

...

Keyword(s):

Whole Blood ◽

Point Of Care ◽

Low Cost ◽

Lateral Flow ◽

Antibody Detection ◽

Lateral Flow Assays ◽

Quantitative Results ◽

Development And Validation ◽

Antibody Tests ◽

Split Luciferase

Current serology tests for SARS-CoV-2 antibodies mainly take the form of enzyme-linked immunosorbent assays or lateral flow assays, with the former being laborious and the latter being expensive and often lacking sufficient sensitivity and scalability. Here we present the development and validation of a rapid, low-cost solution-based assay to detect antibodies in serum, plasma, whole blood, and saliva, using rationally designed split luciferase antibody biosensors (spLUC). This new assay, which generates quantitative results in as short as 5 minutes, substantially reduces the complexity and improves the scalability of COVID-19 antibody tests for point-of-care and broad population testing.

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A Low-Cost, High-Performance System for Fluorescence Lateral Flow Assays

Biosensors ◽

10.3390/bios3040360 ◽

2013 ◽

Vol 3 (4) ◽

pp. 360-373 ◽

Cited By ~ 58

Author(s):

Linda Lee ◽

Eric Nordman ◽

Martin Johnson ◽

Mark Oldham

Keyword(s):

High Performance ◽

Low Cost ◽

Lateral Flow ◽

Lateral Flow Assays ◽

Performance System

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Fundamentals and applications of SERS-based bioanalytical sensing

Nanophotonics ◽

10.1515/nanoph-2016-0174 ◽

2017 ◽

Vol 6 (5) ◽

pp. 831-852 ◽

Cited By ~ 57

Author(s):

Mehmet Kahraman ◽

Emma R. Mullen ◽

Aysun Korkmaz ◽

Sebastian Wachsmann-Hogiu

Keyword(s):

Point Of Care ◽

Low Cost ◽

High Sensitivity ◽

Chemical Information ◽

Label Free ◽

Analytical Technique ◽

Sers Substrates ◽

Interface Surface ◽

Bioanalytical Applications ◽

Care Technology

AbstractPlasmonics is an emerging field that examines the interaction between light and metallic nanostructures at the metal-dielectric interface. Surface-enhanced Raman scattering (SERS) is a powerful analytical technique that uses plasmonics to obtain detailed chemical information of molecules or molecular assemblies adsorbed or attached to nanostructured metallic surfaces. For bioanalytical applications, these surfaces are engineered to optimize for high enhancement factors and molecular specificity. In this review we focus on the fabrication of SERS substrates and their use for bioanalytical applications. We review the fundamental mechanisms of SERS and parameters governing SERS enhancement. We also discuss developments in the field of novel SERS substrates. This includes the use of different materials, sizes, shapes, and architectures to achieve high sensitivity and specificity as well as tunability or flexibility. Different fundamental approaches are discussed, such as label-free and functional assays. In addition, we highlight recent relevant advances for bioanalytical SERS applied to small molecules, proteins, DNA, and biologically relevant nanoparticles. Subsequently, we discuss the importance of data analysis and signal detection schemes to achieve smaller instruments with low cost for SERS-based point-of-care technology developments. Finally, we review the main advantages and challenges of SERS-based biosensing and provide a brief outlook.

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A SARS-CoV-2 aptasensor based on electrochemical impedance spectroscopy and low-cost gold electrode substrates.

10.33774/chemrxiv-2021-08vx4 ◽

2021 ◽

Author(s):

Perrine Lasserre ◽

Banushan Balansethupathy ◽

Vincent J. Vezza ◽

Adrian Butterworth ◽

Alexander MacDonald ◽

...

Keyword(s):

Electrochemical Impedance ◽

Low Cost ◽

Glucose Monitoring ◽

High Sensitivity ◽

Blood Glucose Monitoring ◽

Label Free ◽

Rna Sequences ◽

Point Of Use ◽

Lateral Flow Assays ◽

Impedimetric Biosensor

SARS-CoV-2 diagnostic practices broadly involve either qPCR based nucleic amplification or lateral flow assays (LFAs). qPCR based techniques suffer from the disadvantage of requiring thermal cycling (difficult to implement for low-cost field use) leading to limitation on sample to answer time, the potential to amplify viral RNA sequences after a person is no longer infectious and being reagent intense. LFA performance is restricted by qualitative or semi-quantitative readouts, limits on sensitivity and poor reproducibility. Electrochemical biosensors, and particularly glucose test strips, present an appealing platform for development of biosensing solutions for SARS-CoV-2 as they can be multiplexed and implemented at very low cost at point of use with high sensitivity and quantitative digital readout. This work reports the successful raising of an Opti-mer sequence for the spike protein of SARS-CoV-2 and then development of an impedimetric biosensor which utilises thin film gold sensors on low-cost laminate substrates from home blood glucose monitoring. Clinically relevant detection levels for SARS-CoV-2 are achieved in a simple, label-free measurement format using sample incubation times of 15 minutes. The biosensor developed here is compatible with mass manufacture, is sensitive and low-cost CE marked readout instruments already exist. These findings pave the way to a low cost and mass manufacturable test with the potential to overcome the limitations associated with current technologies.

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In-Situ Integration of 3D C-MEMS Microelectrodes with Bipolar Exfoliated Graphene for Label-Free Electrochemical Cancer Biomarkers Aptasensor

Micromachines ◽

10.3390/mi13010104 ◽

2022 ◽

Vol 13 (1) ◽

pp. 104

Author(s):

Shahrzad Forouzanfar ◽

Nezih Pala ◽

Chunlei Wang

Keyword(s):

High Performance ◽

Microelectromechanical Systems ◽

Point Of Care ◽

High Sensitivity ◽

Label Free ◽

Lab On Chip ◽

Electrochemical Label ◽

Mems Technology ◽

On Chip

The electrochemical label-free aptamer-based biosensors (also known as aptasensors) are highly suitable for point-of-care applications. The well-established C-MEMS (carbon microelectromechanical systems) platforms have distinguishing features which are highly suitable for biosensing applications such as low background noise, high capacitance, high stability when exposed to different physical/chemical treatments, biocompatibility, and good electrical conductivity. This study investigates the integration of bipolar exfoliated (BPE) reduced graphene oxide (rGO) with 3D C-MEMS microelectrodes for developing PDGF-BB (platelet-derived growth factor-BB) label-free aptasensors. A simple setup has been used for exfoliation, reduction, and deposition of rGO on the 3D C-MEMS microelectrodes based on the principle of bipolar electrochemistry of graphite in deionized water. The electrochemical bipolar exfoliation of rGO resolves the drawbacks of commonly applied methods for synthesis and deposition of rGO, such as requiring complicated and costly processes, excessive use of harsh chemicals, and complex subsequent deposition procedures. The PDGF-BB affinity aptamers were covalently immobilized by binding amino-tag terminated aptamers and rGO surfaces. The turn-off sensing strategy was implemented by measuring the areal capacitance from CV plots. The aptasensor showed a wide linear range of 1 pM–10 nM, high sensitivity of 3.09 mF cm−2 Logc−1 (unit of c, pM), and a low detection limit of 0.75 pM. This study demonstrated the successful and novel in-situ deposition of BPE-rGO on 3D C-MEMS microelectrodes. Considering the BPE technique’s simplicity and efficiency, along with the high potential of C-MEMS technology, this novel procedure is highly promising for developing high-performance graphene-based viable lab-on-chip and point-of-care cancer diagnosis technologies.

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Reducing Unspecific Protein Adsorption in Microfluidic Papers Using Fiber-Attached Polymer Hydrogels

Sensors ◽

10.3390/s21196348 ◽

2021 ◽

Vol 21 (19) ◽

pp. 6348

Author(s):

Alexander Ritter von Stockert ◽

Anna Luongo ◽

Markus Langhans ◽

Thomas Brandstetter ◽

Jürgen Rühe ◽

...

Keyword(s):

Protein Transport ◽

Point Of Care ◽

Low Cost ◽

Local Heating ◽

Free Water ◽

Lateral Flow ◽

Paper Strip ◽

Detection Zone ◽

Free Paper ◽

Lateral Flow Assays

Microfluidic paper combines pump-free water transport at low cost with a high degree of sustainability, as well as good availability of the paper-forming cellulosic material, thus making it an attractive candidate for point-of-care (POC) analytics and diagnostics. Although a number of interesting demonstrators for such paper devices have been reported to date, a number of challenges still exist, which limit a successful transfer into marketable applications. A strong limitation in this respect is the (unspecific) adsorption of protein analytes to the paper fibers during the lateral flow assay. This interaction may significantly reduce the amount of analyte that reaches the detection zone of the microfluidic paper-based analytical device (µPAD), thereby reducing its overall sensitivity. Here, we introduce a novel approach on reducing the nonspecific adsorption of proteins to lab-made paper sheets for the use in µPADs. To this, cotton linter fibers in lab-formed additive-free paper sheets are modified with a surrounding thin hydrogel layer generated from photo-crosslinked, benzophenone functionalized copolymers based on poly-(oligo-ethylene glycol methacrylate) (POEGMA) and poly-dimethyl acrylamide (PDMAA). This, as we show in tests similar to lateral flow assays, significantly reduces unspecific binding of model proteins. Furthermore, by evaporating the transport fluid during the microfluidic run at the end of the paper strip through local heating, model proteins can almost quantitatively be accumulated in that zone. The possibility of complete, almost quantitative protein transport in a µPAD opens up new opportunities to significantly improve the signal-to-noise (S/N) ratio of paper-based lateral flow assays.

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