Dielectric Modulated GaAs1-xSbX FinFET as a Label-Free Biosensor: Device Proposal and Investigation

Serological tests are essential for the control and management of COVID-19 pandemic, not only for current and historical diagnostics but especially for surveillance, epidemiological, and acquired immunity studies. Clinical COVID-19 serology is routinely performed by enzymatic or chemiluminescence immunoassays (i.e., ELISA or CLIA), which provide good sensitivities at the expense of relatively long turnaround times and specialized laboratory settings. Rapid serological tests, based on lateral flow assays, have also been developed and widely commercialized, but they suffer from limited reliability due to relatively low sensitivity and specificity. We have developed and validated a direct serological biosensor assay employing proprietary technology based on Surface Plasmon Resonance (SPR). The biosensor offers a rapid -less than 15 min- identification and quantification of SARS-CoV-2 antibodies directly in clinical samples, without the need of any signal amplification. The portable plasmonic biosensor device employs a custom-designed multi-antigen sensor biochip, combining the two main viral antigens (RBD peptide and N protein), for simultaneous detection of human antibodies targeting both antigens. The SPR serology assay reaches detection limits in the low ng mL-1 range employing polyclonal antibodies as standard, which are well below the commonly detected antibody levels in COVID-19 patients. The assay has also been implemented employing the first WHO approved anti-SARS-CoV-2 immunoglobulin standard. We have carried out a clinical validation with COVID-19 positive and negative samples (n=120) that demonstrates the excellent diagnostic sensitivity (99%) and specificity (100%). This positions our biosensor device as an accurate, robust, and easy-to-use diagnostics tool for rapid and reliable COVID-19 serology to be employed both at laboratory and decentralized settings for the management of COVID-19 patients and for the evaluation of immunological status during vaccination, treatment or in front of emerging variants.<br>

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Label-Free Plasmonic Biosensor for Rapid, Quantitative, and Highly Sensitive COVID-19 Serology: Implementation and Clinical Validation

10.26434/chemrxiv.14595654 ◽

2021 ◽

Author(s):

Olalla Calvo-Lozano ◽

MIquel Sierra ◽

Maria Soler ◽

M.-Carmen Estevez ◽

luis Chiscano-camon ◽

...

Keyword(s):

Polyclonal Antibodies ◽

Simultaneous Detection ◽

Clinical Samples ◽

Clinical Validation ◽

Label Free ◽

Serological Tests ◽

N Protein ◽

Lateral Flow Assays ◽

Low Sensitivity ◽

Biosensor Device

Serological tests are essential for the control and management of COVID-19 pandemic, not only for current and historical diagnostics but especially for surveillance, epidemiological, and acquired immunity studies. Clinical COVID-19 serology is routinely performed by enzymatic or chemiluminescence immunoassays (i.e., ELISA or CLIA), which provide good sensitivities at the expense of relatively long turnaround times and specialized laboratory settings. Rapid serological tests, based on lateral flow assays, have also been developed and widely commercialized, but they suffer from limited reliability due to relatively low sensitivity and specificity. We have developed and validated a direct serological biosensor assay employing proprietary technology based on Surface Plasmon Resonance (SPR). The biosensor offers a rapid -less than 15 min- identification and quantification of SARS-CoV-2 antibodies directly in clinical samples, without the need of any signal amplification. The portable plasmonic biosensor device employs a custom-designed multi-antigen sensor biochip, combining the two main viral antigens (RBD peptide and N protein), for simultaneous detection of human antibodies targeting both antigens. The SPR serology assay reaches detection limits in the low ng mL-1 range employing polyclonal antibodies as standard, which are well below the commonly detected antibody levels in COVID-19 patients. The assay has also been implemented employing the first WHO approved anti-SARS-CoV-2 immunoglobulin standard. We have carried out a clinical validation with COVID-19 positive and negative samples (n=120) that demonstrates the excellent diagnostic sensitivity (99%) and specificity (100%). This positions our biosensor device as an accurate, robust, and easy-to-use diagnostics tool for rapid and reliable COVID-19 serology to be employed both at laboratory and decentralized settings for the management of COVID-19 patients and for the evaluation of immunological status during vaccination, treatment or in front of emerging variants.<br>

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Label-Free Plasmonic Biosensor for Rapid, Quantitative, and Highly Sensitive COVID-19 Serology: Implementation and Clinical Validation

10.26434/chemrxiv.14595654.v1 ◽

2021 ◽

Author(s):

Olalla Calvo-Lozano ◽

MIquel Sierra ◽

Maria Soler ◽

M.-Carmen Estevez ◽

luis Chiscano-camon ◽

...

Keyword(s):

Polyclonal Antibodies ◽

Simultaneous Detection ◽

Clinical Samples ◽

Clinical Validation ◽

Label Free ◽

Serological Tests ◽

N Protein ◽

Lateral Flow Assays ◽

Low Sensitivity ◽

Biosensor Device

Serological tests are essential for the control and management of COVID-19 pandemic, not only for current and historical diagnostics but especially for surveillance, epidemiological, and acquired immunity studies. Clinical COVID-19 serology is routinely performed by enzymatic or chemiluminescence immunoassays (i.e., ELISA or CLIA), which provide good sensitivities at the expense of relatively long turnaround times and specialized laboratory settings. Rapid serological tests, based on lateral flow assays, have also been developed and widely commercialized, but they suffer from limited reliability due to relatively low sensitivity and specificity. We have developed and validated a direct serological biosensor assay employing proprietary technology based on Surface Plasmon Resonance (SPR). The biosensor offers a rapid -less than 15 min- identification and quantification of SARS-CoV-2 antibodies directly in clinical samples, without the need of any signal amplification. The portable plasmonic biosensor device employs a custom-designed multi-antigen sensor biochip, combining the two main viral antigens (RBD peptide and N protein), for simultaneous detection of human antibodies targeting both antigens. The SPR serology assay reaches detection limits in the low ng mL-1 range employing polyclonal antibodies as standard, which are well below the commonly detected antibody levels in COVID-19 patients. The assay has also been implemented employing the first WHO approved anti-SARS-CoV-2 immunoglobulin standard. We have carried out a clinical validation with COVID-19 positive and negative samples (n=120) that demonstrates the excellent diagnostic sensitivity (99%) and specificity (100%). This positions our biosensor device as an accurate, robust, and easy-to-use diagnostics tool for rapid and reliable COVID-19 serology to be employed both at laboratory and decentralized settings for the management of COVID-19 patients and for the evaluation of immunological status during vaccination, treatment or in front of emerging variants.<br>

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Label-free, mass-sensitive single-molecule imaging using interferometric scattering microscopy

Essays in Biochemistry ◽

10.1042/ebc20200023 ◽

2020 ◽

Author(s):

Nikolas Hundt

Keyword(s):

Single Molecule ◽

Cellular Systems ◽

Single Molecule Imaging ◽

Label Free ◽

Measurement Sensitivity ◽

Mass Distributions ◽

Quantitative Measurements ◽

Contrast Mechanism ◽

Cellular Components ◽

Scattering Signal

Abstract Single-molecule imaging has mostly been restricted to the use of fluorescence labelling as a contrast mechanism due to its superior ability to visualise molecules of interest on top of an overwhelming background of other molecules. Recently, interferometric scattering (iSCAT) microscopy has demonstrated the detection and imaging of single biomolecules based on light scattering without the need for fluorescent labels. Significant improvements in measurement sensitivity combined with a dependence of scattering signal on object size have led to the development of mass photometry, a technique that measures the mass of individual molecules and thereby determines mass distributions of biomolecule samples in solution. The experimental simplicity of mass photometry makes it a powerful tool to analyse biomolecular equilibria quantitatively with low sample consumption within minutes. When used for label-free imaging of reconstituted or cellular systems, the strict size-dependence of the iSCAT signal enables quantitative measurements of processes at size scales reaching from single-molecule observations during complex assembly up to mesoscopic dynamics of cellular components and extracellular protrusions. In this review, I would like to introduce the principles of this emerging imaging technology and discuss examples that show how mass-sensitive iSCAT can be used as a strong complement to other routine techniques in biochemistry.

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A microfluidic device with integrated impedance detection for λ-DNA

MRS Proceedings ◽

10.1557/proc-773-n6.5 ◽

2003 ◽

Vol 773 ◽

Cited By ~ 1

Author(s):

Myung-Il Park ◽

Jonging Hong ◽

Dae Sung Yoon ◽

Chong-Ook Park ◽

Geunbae Im

Keyword(s):

Microfluidic Device ◽

Electrochemical Impedance ◽

Direct Detection ◽

Full Potential ◽

Label Free ◽

Buffer Solution ◽

Detection Systems ◽

Significant Difference ◽

Detection Of Biomolecules ◽

Impedance Magnitude

AbstractThe large optical detection systems that are typically utilized at present may not be able to reach their full potential as portable analysis tools. Accurate, early, and fast diagnosis for many diseases requires the direct detection of biomolecules such as DNA, proteins, and cells. In this research, a glass microchip with integrated microelectrodes has been fabricated, and the performance of electrochemical impedance detection was investigated for the biomolecules. We have used label-free λ-DNA as a sample biomolecule. By changing the distance between microelectrodes, the significant difference between DW and the TE buffer solution is obtained from the impedance-frequency measurements. In addition, the comparison for the impedance magnitude of DW, the TE buffer, and λ-DNA at the same distance was analyzed.

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