Accurate, High-Throughput, and Affordable Nucleic Acid Sequencing Technology

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Project Summary / Abstract Remarkable progress in cancer immunotherapy, and decreasing cost of Next Generation Sequencing (NGS) diagnostics, have sparked clinical tests targeting tumor-immune cell interactions using genomic tools. Non-small cell lung cancer (NSCLC) exemplifies precision medicine with multiple FDA-approved biomarkers. Despite these advancements, the practical use of NGS remains limited. Instrument setup and operating costs are prohibitive for the majority of smaller labs. Patient samples thus need to be shipped to specific labs set up for conducting the test, which results in longer turnaround time and higher costs. Short turnaround time plays a vital role in clinical decisions. The availability of NGS at local CLIA (Clinical Laboratory Improvement Amendments) labs will take us one step closer to truly personalized healthcare. This project develops a first-of-its-kind biosensor chip for long-read nucleic acid sequencing. The proposed lab- on-chip technology allows the parallel detection of incorporated bases into a growing strand of DNA. The technology requires a relatively low capital investment to allow smaller laboratories to acquire the instrument and provide medical professionals with critical information, such as the ideal timing of future injected doses and any potential side effects. The critical innovations behind the proposed technology include its high-throughput biosensor architecture, the ability to scale-up manufacturing using existing silicon foundries, simple operation and product design, and real-time data analysis. Moreover, the commercialization of the proposed technology is facilitated by a mature semiconductor industry to achieve this high level of multiplexing in a small form factor. The proposed project focuses on engineering and optimization of the proposed biosensor platform and iterative development using a well-characterized cytomegalovirus CDR3β sequence. This Phase I project will use synthetic templates for technology validation and calculation of the consensus accuracy. Successful completion of the project will provide a proof-of-concept, informing the productization and commercialization of the technology. The global DNA sequencing market is expected to grow to $25B in 2025 at a CAGR of 19.0%, with a potential immune monitoring sector worth over $3B. If successful, the proposed technology will be a groundbreaking development in clinical NGS diagnostics, especially for early and accurate profiling of the T cell receptor repertoire in fast-developing infectious diseases. More affordable and available sequencing will advance the effectiveness of the treatment for cancer and infectious diseases for millions of people around the world.