Nanoscale biosensor arrays for biomolecule analysis

Molariti Inc, Cambridge MA

Investigators

Abstract

Project Summary/Abstract The demand for more sensitive, high-throughput, accurate, and quantitative methods to analyze biomolecules is growing due to its potential impact in healthcare. For example, early detection of biomarkers for diseases such as cancer, infectious diseases, and genetic disorders can lead to better patient outcomes. This would be possible through sensitive identification and quantification of biomolecules. Identifying novel proteins in their native state from complex samples could enable biomarker discovery, drug target identification, personalized medicine, and advancements in disease understanding and treatment. Many lab tools that have existed for decades to serve some of these applications (E.g., UV-Vis spectroscopy, fluorometry, electrophoresis, and chromatography) are limited in throughput, sensitivity, resolution, required sample volume, sample loss, etc. Hence, high-throughput ultra-sensitive biomolecule analyzers are necessary to improve healthcare significantly. A Nanopore is an excellent structure for sensitive, single molecule analysis of biomolecules. Despite the initial success of biological nanopores for DNA sequencing, its utility in a broad range of applications analyzing biomolecules has been stymied due to its limited size range and poor stability. Solid-state nanopores, on the other hand, show great promise featuring flexibility in pore sizes and materials. However, current fabrication methods do not scale, are expensive, and have stringent limitations. There is a need for a breakthrough in nanopore fabrication technology to create nanopores at scale and drive the development of myriad other research tools involving sensitive, high- throughput, accurate, and quantitative biomolecule analysis. We are proposing a novel solid-state nanopore array chip technology, enabling a broad suite of biomedical research tools. Current methods fabricate one pore at a time using expensive equipment (e.g., Transmission Electron Microscope, Focused Ion or Electron Beam), or complex optical systems, requiring skilled expertise. Newer methods using controlled dielectric breakdown (CDB) are still limited by constraints on film thickness, lack of control over the location and number of pores, and the use of electrolytes with stringent pH requirements. If successful, our fabrication approach would dramatically decrease the cost of nanopore fabrication, relieving a bottleneck in the development of many sensitive high- throughput biomolecule analysis instruments. Our aim in this work is to systematically study the development of our nanopore array chip technology that surpasses current limitations. By utilizing our nanopore technology to drive applications in biomolecule analysis, we can achieve orders of magnitude improvement over the current state-of-the-art in sensitivity, process thousands of samples simultaneously, and reduce sample volume requirements by at least 10x with minimal sample loss while providing accurate and quantitative results. Thus, we believe our proposed work will broadly impact biomedical research by enabling nanopores to reach their full potential in sensitive and high-throughput biomolecule analysis applications.