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Digital immunoassay for biomarker concentration quantification using solid-state nanopores
Liqun He1, Daniel R Tessier1, Kyle Briggs1
1Department of Physics, University of Ottawa, Ottawa, Canada.
Nature Communications
|September 10, 2021
Summary
This study introduces a digital immunoassay using DNA nanostructures and nanopores for precise protein biomarker quantification. This method enables accurate digital diagnostics for precision medicine, even in complex biological samples.
Area of Science:
- Biotechnology
- Nanotechnology
- Molecular Diagnostics
Background:
- Single-molecule counting offers unparalleled accuracy for biomarker concentration determination, driving the development of digital diagnostic platforms for precision medicine.
- Solid-state nanopores, as fully electronic sensors with single-molecule sensitivity, are theoretically ideal for this application but face challenges in protein sensing.
- Existing nanopore sensing methods struggle with specificity, sensitivity, and consistency when analyzing proteins in complex biological fluids.
Purpose of the Study:
- To develop a robust digital immunoassay scheme for reliable protein concentration quantification in complex biofluids.
- To overcome the limitations of solid-state nanopores in specificity, sensitivity, and consistency for protein detection.
- To establish a proof-of-concept for a digital diagnostic approach using DNA nanostructures as protein proxies.
Main Methods:
- A magnetic bead-based sandwich immunoassay was employed to capture target proteins.
- DNA nanostructures were utilized as identifiable proxies, signaling the presence ('1') or absence ('0') of the captured target protein.
- Solid-state nanopores were used as the sensing platform for detecting these DNA nanostructures.
Main Results:
- The digital immunoassay scheme reliably quantified protein concentrations in complex biofluids.
- The method demonstrated high sensitivity, achieving quantification down to the high femtomolar range for thyroid-stimulating hormone in human serum.
- The approach successfully addressed specificity, sensitivity, and consistency challenges inherent in nanopore protein sensing.
Conclusions:
- The developed digital immunoassay scheme offers a reliable method for protein quantification using solid-state nanopores.
- This approach, utilizing DNA nanostructures as proxies, overcomes key challenges in nanopore-based protein sensing.
- Further optimization holds promise for developing sensitive, high-dynamic-range diagnostic tools for point-of-care applications in precision medicine.
