Reprogrammable Nucleic Acid-Based Biomarker Measurements

A. Balijepalli, J.M. Majikes, J.A. Liddle, P.M. Vallone, A.J. Kearsley
National Institute of Standards and Technology,
United States

Keywords: DNA nanotechnology, CMOS, viral diagnostics, bioelectronics, bio sensing


Nucleic acids (DNA and RNA) are the fundamental building blocks of life. Mutations in these molecules, from inherited or environmental factors, result in a constantly changing array of health threats ranging from cancer, autoimmune diseases, and in pathogens, the ability to naturally select mutations which allow them to effectively evade the immune system. Therefore, surveillance of nucleic acids is a vital tool for monitoring public health. However, rapid mutations in biomarkers can outpace the development and deployment of high-specificity diagnostic polymerase chain reaction (PCR) tests. The need for a novel and agile biomarker metrology is evident in the current pandemic, where the spread of SARS CoV-2 mutants has challenged the traditional diagnostic testing infrastructure. To meet this need, we will create a new biomarker metrology that combines DNA nanostructure-enhanced detectors with arrays of electronic sensors and artificial intelligence (AI) frameworks, to give it flexibility and to allow it to be rapidly reprogrammed in the field. Our approach1,2 will have high sensitivity without the use of PCR, a widely used sample enrichment technique that has the disadvantage of both a significant wait for analysis results, a dependence on perfect, or near perfect, target-analyte specificity, and system complexity. By using DNA nanotechnology, we will engineer arrays of electronic sensors that generates unique molecular signatures for different analytes. High-dimensional data comprising these signatures are ideally suited for decoding with AI methods that will be designed to also quantify measurement errors and uncertainty (UQ) and improve trustworthiness. Our first-of-a-kind, reprogrammable label- and PCR-free biomarker detection chip will allow a disruptive improvement in medical diagnostics and surveillance of future public health threats. References 1. Arvind Balijepalli & Jacob Majikes. DNA Nanotechnology-based Biomarker Measurement Platform, Patent Application No. US20210403988A1 2. Arvind Balijepalli et al. Agile Nucleic Acid-Based Biomarker Metrology, Provisional Patent Application No. US63/212,753