Towards a point-of-care nanoplasmonic biosensor for rapid and multiplexed detection of pathogenic infections

Paper-based lateral flow devices (LFDs) are regarded as ideal low-cost diagnostic solutions for point-of-care (POC) scenarios that allow rapid detection of a single analyte within a fluidic sample, and have been in common use for a decade. In recent years, there has been an increasing need for rapid and simultaneous detection of multiple analytes present within a single sample and to facilitate this, we report here a novel solution—detection using a multi-path LFD created via the precise partitioning of the single flow-path of a standard LFD using our previously reported laser direct-write (LDW) technique. The multiple flow-paths allow the simultaneous detection of the different analytes individually within each of the parallel channels without any cross-reactivity. The appearance of coloured test lines in individual channels indicates the presence of the different analytes within a sample. We successfully present the use of a LDW-patterned multi-path LFD for multiplexed detection of a biomarker panel comprising C-reactive protein (CRP) and Serum amyloid A-1 (SAA1), used for the diagnosis of bacterial infections. Overall, we demonstrate the use of our LDW technique in the creation of a novel LFD that enables multiplexed detection of two inflammation markers within a single LFD providing a detection protocol that is comparatively more efficient than the standard sequential multiplexing procedure.

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A hydrogel sensor-based microfluidic platform for the quantitative and multiplexed detection of fertility markers for point-of-care immunoassays

Analytical Methods ◽

10.1039/c8ay02641f ◽

2019 ◽

Vol 11 (12) ◽

pp. 1639-1650 ◽

Cited By ~ 3

Author(s):

Satish Kalme ◽

Srinivasan Kandaswamy ◽

Anusha Chandrasekharmath ◽

Reeta Katiyar ◽

Gokul Prasath Rajamanickam ◽

...

Keyword(s):

Microfluidic Device ◽

Point Of Care ◽

Microfluidic Platform ◽

Multiplexed Detection ◽

Hydrogel Particle ◽

Multiplexed Immunoassay ◽

Porous Hydrogel

We report a new point-of-care, multiplexed immunoassay platform based on 3D porous hydrogel particle sensors embedded into a plastic microfluidic device.

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Point‐of‐Care Platform for Rapid Multiplexed Detection of SARS‐CoV‐2 Variants and Respiratory Pathogens

Advanced Materials Technologies ◽

10.1002/admt.202101013 ◽

2022 ◽

pp. 2101013

Author(s):

Alexander Y. Trick ◽

Fan‐En Chen ◽

Liben Chen ◽

Pei‐Wei Lee ◽

Alexander C. Hasnain ◽

...

Keyword(s):

Point Of Care ◽

Respiratory Pathogens ◽

Multiplexed Detection

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Companion and Point-of-Care Sensor System for Rapid Multiplexed Detection of a Panel of Infectious Disease Markers

SLAS TECHNOLOGY Translating Life Sciences Innovation ◽

10.1177/2472630317696779 ◽

2017 ◽

pp. 247263031769677

Author(s):

Anjan Panneer Selvam ◽

Shalini Prasad

Keyword(s):

Whole Blood ◽

Dynamic Range ◽

Electrochemical Impedance ◽

Limit Of Detection ◽

Point Of Care ◽

Lipoteichoic Acid ◽

Impedance Change ◽

Label Free ◽

Nylon Membrane ◽

Multiplexed Detection

A nanochannel-based electrochemical biosensor has been demonstrated for rapid and multiplexed detection of a panel of three biomarkers associated with rapid detection of sepsis. The label-free biosensor detected procalcitonin (PCT), lipoteichoic acid (LTA), and lipopolysaccharide (LPS) from human whole blood. The biosensor comprises a nanoporous nylon membrane integrated onto a microelectrode sensor platform for nanoconfinement effects. Charge perturbations due to biomarker binding are recorded as impedance changes using electrochemical impedance spectroscopy. The measured impedance change is used to quantitatively determine the concentration of the three biomarkers using antibody receptors from the tested sample. We were successful in detecting and quantifying the three biomarkers from whole blood. The limit of detection was 0.1 ng/mL for PCT and 1 µg/mL for LPS and LTA. The sensor was able to demonstrate a dynamic range of detection from 01.1 ng/mL to 10 µg/mL for PCT and from 1 µg/mL to 1000 µg/mL for LPS and LTA biomarkers. This novel technology has promising preliminary results toward the design of sensors for rapid and sensitive detection of the three panel biomarkers in whole blood toward diagnosis and classification of sepsis.

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An on-chip valve-assisted microfluidic chip for quantitative and multiplexed detection of biomarkers

Analytical Methods ◽

10.1039/c8ay00682b ◽

2018 ◽

Vol 10 (21) ◽

pp. 2470-2480 ◽

Cited By ~ 3

Author(s):

Binfeng Hu ◽

Yong Liu ◽

Jinqi Deng ◽

Lei Mou ◽

Xingyu Jiang

Keyword(s):

Microfluidic Chip ◽

Point Of Care ◽

Microfluidic Chips ◽

Portable Instrument ◽

Multiplexed Detection ◽

On Chip ◽

Detection Of Biomarkers

A point-of-care immunoassay platform including on-chip valve-assisted microfluidic chips and a portable instrument for quantitative and multiplexed detection of biomarkers.

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A nanofluidic device for rapid and multiplexed SARS-CoV-2 serological antibody detection

10.21203/rs.3.rs-537056/v1 ◽

2021 ◽

Author(s):

Thomas Mortelmans ◽

Dimitrios Kazazis ◽

Celestino Padeste ◽

Philipp Berger ◽

Xiaodan Li ◽

...

Keyword(s):

Influenza A ◽

Point Of Care ◽

Simultaneous Detection ◽

High Sensitivity ◽

Modern Society ◽

Antibody Detection ◽

Multiplexed Detection ◽

Viral Spread ◽

Point Of Care Diagnostics ◽

Nanofluidic Device

Abstract The outbreak of COVID-19 has led to a substantial death toll and has hindered the functioning of modern society, sending the world into a medical and economic crisis1,2. This underlined the importance of point-of-care diagnostics, as well as accurate, cost-effective serological antibody tests as well as point-of-care diagnostics to monitor the viral spread and contain pandemics and endemics. Here, we present a three-dimensional (3D) nanofluidic device for rapid and multiplexed detection of viral antibodies. The device is designed to size-dependently immobilize particles from a multi-particle mixture at predefined positions in nanochannels through capillary forces only, resulting in distinct trapping lines. We show that individual lines can be used as an on-chip fluorescence-linked immunosorbent assay for multiplexed detection of serological immunoglobulin antibodies against viral proteins with high sensitivity. Further device versatility is exhibited by on-bead color multiplexing for simultaneous detection of IgG and IgM antibodies in convalescent human serum and by concurrent detection of anti-spike (SARS-CoV-2) and anti-hemagglutinin (Influenza A) antibodies. The device’s applications can be further extended to detect a plethora of diseases simultaneously in a reliable and straightforward manner.

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Minimally instrumented SHERLOCK (miSHERLOCK) for CRISPR-based point-of-care diagnosis of SARS-CoV-2 and emerging variants

Science Advances ◽

10.1126/sciadv.abh2944 ◽

2021 ◽

Vol 7 (32) ◽

pp. eabh2944

Author(s):

Helena de Puig ◽

Rose A. Lee ◽

Devora Najjar ◽

Xiao Tan ◽

Luis R. Soekensen ◽

...

Keyword(s):

Point Of Care ◽

Low Cost ◽

Smartphone Application ◽

Modular System ◽

User Needs ◽

Multiplexed Detection ◽

Highly Sensitive ◽

Current Point ◽

Automated Interpretation ◽

User Actions

The COVID-19 pandemic highlights the need for diagnostics that can be rapidly adapted and deployed in a variety of settings. Several SARS-CoV-2 variants have shown worrisome effects on vaccine and treatment efficacy, but no current point-of-care (POC) testing modality allows their specific identification. We have developed miSHERLOCK, a low-cost, CRISPR-based POC diagnostic platform that takes unprocessed patient saliva; extracts, purifies, and concentrates viral RNA; performs amplification and detection reactions; and provides fluorescent visual output with only three user actions and 1 hour from sample input to answer out. miSHERLOCK achieves highly sensitive multiplexed detection of SARS-CoV-2 and mutations associated with variants B.1.1.7, B.1.351, and P.1. Our modular system enables easy exchange of assays to address diverse user needs and can be rapidly reconfigured to detect different viruses and variants of concern. An adjunctive smartphone application enables output quantification, automated interpretation, and the possibility of remote, distributed result reporting.

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Multiplexed detection of bacterial nucleic acids using Cas13 in droplet microarrays

10.1101/2021.11.12.468388 ◽

2021 ◽

Author(s):

Sri Gowtham Thakku ◽

Cheri M Ackerman ◽

Cameron Myhrvold ◽

Roby P Bhattacharyya ◽

Jonathan Livny ◽

...

Keyword(s):

Nucleic Acid ◽

Sensitivity And Specificity ◽

Health Management ◽

Point Of Care ◽

Bacterial Species ◽

Bacterial Pathogen ◽

Antibiotic Resistance Genes ◽

Detection Methods ◽

Nucleic Acid Detection ◽

Multiplexed Detection

Rapid and accurate diagnosis of infections is fundamental to individual patient care and public health management. Nucleic acid detection methods are critical to this effort, but are limited either in the breadth of pathogens targeted or by the expertise and infrastructure required. We present here a high-throughput system that enables rapid identification of bacterial pathogens, bCARMEN, which utilizes: (1) modular CRISPR-Cas13-based nucleic acid detection with enhanced sensitivity and specificity; and (2) a droplet microfluidic system that enables thousands of simultaneous, spatially multiplexed detection reactions at nanoliter volumes; and (3) a novel pre-amplification strategy that further enhances sensitivity and specificity. We demonstrate bCARMEN is capable of detecting and discriminating 52 clinically relevant bacterial species and several key antibiotic resistance genes. We further develop a proof of principle system for use with stabilized reagents and a simple workflow with optical readout using a cell phone camera, opening up the possibility of a rapid point-of-care multiplexed bacterial pathogen identification and antibiotic susceptibility testing.

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