Label-free quantification of molecular biomarkers using optical-trapping-assisted nanopore sensing

S. M. Saiduzzaman; Mohammad Julker Neyen Sampad; Zachary J. Walker; Tanner N. Wells; Jesse X. Wayment; Ephraim M. Ong; Spencer T. Seiler; Thomas D. Yuzvinsky; Sofie R. Salama; David Haussler; Aaron R. Hawkins; Holger Schmidt

doi:10.1117/12.3028619

3 October 2024 Label-free quantification of molecular biomarkers using optical-trapping-assisted nanopore sensing

S. M. Saiduzzaman, Mohammad Julker Neyen Sampad, Zachary J. Walker, Tanner N. Wells, Jesse X. Wayment, Ephraim M. Ong, Spencer T. Seiler, Thomas D. Yuzvinsky, Sofie R. Salama, David Haussler, Aaron R. Hawkins, Holger Schmidt

Author Affiliations +

Proceedings Volume PC13112, Optical Trapping and Optical Micromanipulation XXI; PC131120Z (2024) https://doi.org/10.1117/12.3028619
Event: Nanoscience + Engineering, 2024, San Diego, California, United States

Abstract

Integrated optofluidic nanopore sensor technologies have enabled label-free quantification of molecular biomarkers by digital detection of target biomolecules with the electrical translocation signal created during passage through a nanoscale opening. The approach utilizes planar waveguide-based optical trapping combined with a customized microfluidic channel geometry for million-fold target concentration enhancement underneath a nanopore. The optofluidic device design is optimized for better optical trapping performance utilizing both gradient and scattering optical forces. Combined with a target-specific bioassay, this simple, direct, and highly sensitive detection method enables amplification-free and calibration-free biomarker quantification. Using this platform, we show viral load day progression of Zika and SARS-CoV-2 infections from different biofluids in primate models across the clinically relevant concentrations range (five orders) down to 10 aM –comparable to and sometimes improving upon qRT-PCR results. We also report the use of this integrated sensor for extracellular vesicle cargo monitoring from cerebral organoids grown in conditioned media.

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S. M. Saiduzzaman, Mohammad Julker Neyen Sampad, Zachary J. Walker, Tanner N. Wells, Jesse X. Wayment, Ephraim M. Ong, Spencer T. Seiler, Thomas D. Yuzvinsky, Sofie R. Salama, David Haussler, Aaron R. Hawkins, and Holger Schmidt "Label-free quantification of molecular biomarkers using optical-trapping-assisted nanopore sensing", Proc. SPIE PC13112, Optical Trapping and Optical Micromanipulation XXI, PC131120Z (3 October 2024); https://doi.org/10.1117/12.3028619

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KEYWORDS

Nanopores

Optical tweezers

Target detection

Optofluidics

Planar waveguides

Scattering

Sensor technology

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