Our group has laid the groundwork in developing a unique, nanopore based method for DNA sequencing by nanopore induced photon emission (SNIPE), which utilizes optical detection rather than the more ubiquitous electrical detection. Our approach is superior to other nanopore approaches as the readout does not involve enzymes, parallelization is straightforward, and the readout is non-destructive. In this grant we propose three distinct aims (developed in parallel), which when brought together, will enable DNA sequencing at an unprecedented scale in terms of speed (>2 10^6 bases/s,) and extremely low cost.
Our first aim i s to dramatically increase the throughput, speed and accuracy of SNIPE. In order to achieve this, we will concentrate our efforts on parallelization of the system through arrays of nanopores (up to 100x100), transformation of the readout from 2 to 4 colors, and increasing the S/B of the readout.
Our second Aim i s to develop and optimize our proprietary DNA conversion approach, Circular DNA conversion (CDC). We plan on achieving this first though automation and optimization of CDC using a commercially available benchtop system. Post CDC optimization, we plan on developing a microfluidic device capable of converting an entire human genome.
Our third Aim i s the development of data analysis algorithms needed for base calling, consensus building, sequence assembly, and error proofing. In completing these three aims we will have achieved in developing a radically new, cost-effective DNA sequencing platform, capable of long read lengths, high speed, and high accuracy. This is expected to have a wide-ranging impact on both basic and applied biomedical research and personalized healthcare.

Public Health Relevance

The extraordinary broad impact of ultra-low cost sequencing on biomedical research, comparative genomics and cancer biology, is driving the development of a plurality of DNA sequencing methods. Our group has been developing a nanopore DNA sequencing method that utilizes optical detection from hundreds of nanopores, as the molecules are pulled electrophoretically driven through the pores. This proposal will allow us to develop this method to address the $1,000 genome challenge.

National Institute of Health (NIH)
National Human Genome Research Institute (NHGRI)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZHG1-HGR-N (M1))
Program Officer
Schloss, Jeffery
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Boston University
Engineering (All Types)
Schools of Engineering
United States
Zip Code
Larkin, Joseph; Henley, Robert Y; Muthukumar, Murugappan et al. (2014) High-bandwidth protein analysis using solid-state nanopores. Biophys J 106:696-704
Anderson, Brett N; Muthukumar, Murugappan; Meller, Amit (2013) pH tuning of DNA translocation time through organically functionalized nanopores. ACS Nano 7:1408-14
Squires, Allison H; Hersey, Joseph S; Grinstaff, Mark W et al. (2013) A nanopore-nanofiber mesh biosensor to control DNA translocation. J Am Chem Soc 135:16304-7
Singer, Alon; Rapireddy, Srinivas; Ly, Danith H et al. (2012) Electronic barcoding of a viral gene at the single-molecule level. Nano Lett 12:1722-8
Singer, Alon; McNally, Ben; Torre, Ruby Dela et al. (2012) DNA sequencing by nanopore-induced photon emission. Methods Mol Biol 870:99-114