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We are developing methods and technology to detect, characterize, and identify biological molecules. Our focus is primarily on addressing next generation health care applications (e.g., early cancer detection, DNA sequencing) using advanced single-molecule detection techniques. More recent efforts are directed to the identification of RNA and proteins at low copy number. Realization of these new measurement tools could prove useful for personalize medicine applications, early cancer detection, and new drugs against infectious bacteria and other forms of disease.

Technical Goals:

  • develop the measurement science required to address next generation health care applications
  • determine the mechanisms by which bacteria infect and kill cells
  • develop new methods to determine membrane protein structure


NIST’s concept for a portable Point of Care device for personalized medical applications.

Figure 1. NIST's concept for a portable Point of Care device for personalized medical applications. The ability to simultaneously quantitate thousands of different types of protein in blood will dramatically change disease detection and management, as did the electronic blood glucose meter late last century.


Every person is unique, and that holds true for how each of us respond to therapeutic drugs. Pharmaceutical and health care industries currently lack measurement tools to determine whether such treatments will be effective, harm or even cause the death of individual patients. To address this issue, we pioneered and developed an electronic nanopore-based method for single molecule metrology. The technology is currently being used to sequence DNA, and will hopefully prove useful to rapidly identify thousands of different proteins in blood. In addition to aiding the next generation of personalized health care applications, these methods should also provide insight into fundamental cellular properties, which could lead to understanding the molecular basis of disease.

We also seek to solve, in part, a long-outstanding problem of determining the structures of membrane proteins, which is crucial for the cost-efficient development of pharmaceutical therapeutic agents.

Major Accomplishments:


  • Developed a novel method to detect and physically characterize single metallic nanoparticles
  • Showed the ability to electronically discriminate between different neurotransmitters
  • Released software for single molecule state detection (highly relevant for DNA sequencing apps)


  • Developed a method, based on physics and circuit theory, to discriminate between subtly different molecules
  • Presented Keynote/Plenary opening lecture at the 2014 International High Performance Liquid Chromatography Conference
  • Submitted several provisional patent applications for a process to identify individual proteins


  • Demonstrated the ability to rapidly heat single molecules and measure their response to temperature jumps; a technology that will support many applications including discriminating between subtly different molecules, understanding the mechanism of protein folding, etc.
  • Demonstrated experimentally a potential mechanism by which anthrax toxins kill cells
  • Critically evaluated a proposed DNA sequencing technology

Nanopore-based DNA Sequencing-by-Synthesis Technology.

Figure 2. Nanopore-based DNA Sequencing-by-Synthesis Technology. In collaboration with Columbia University, we demonstrated initial proof of concept for separating polymer tags that uniquely represent the 4 different DNA bases. Our collaboration has been extended to include a small company.

Single molecule mass Spectrometry (Image courtesy of Jeffrey Aarons)
Figure 3. Single Molecule “Mass Spectrometry”.  The size and amount of charged adsorbed onto a single molecule is measured by the degree it reduces the flow of ions through a nanometer-scale pore.

Lead Organizational Unit:



  • Genia Technologies/Roche, Electronic BioSciences, Ionera, Nanion, U.S. Army Medical Research Institute for Infectious Diseases, Columbia University, University of Freiburg Germany, Wheaton College, Virginia Commonwealth University

Facilities/Tools Used:

We have developed, or helped develop cutting-edge biomolecule measurement capabilities. These include:

  • Improvements to single molecule high-bandwidth FET electrophysiology amplifiers (enables single molecule detection, characterization, & identification; polymer physics, single enzyme kinetics, etc.)
  • custom optical & electrical measurements of intermolecular binding (surface plasmon resonance/electrochemical impedance spectroscopy)
  • custom instrumentation for rapidly heating single molecules and measuring their response. This provides a remarkable opportunity to measure the thermodynamic & kinetic properties of single molecules
  • Langmuir-Blodgett trough for measuring the interaction between lipids and lipids and proteins in a monomolecular thin film, and chemical synthesis laboratory

Other External Facilities:

We are collaborating with small companies to develop the next generation of electronic amplifiers (Electronic BioSciences, CA) and biomembrane mimic chips for electrophysiology (Ionera; Freiburg, Germany), and collaborate with a world-class chemical synthesis laboratory (Columbia University).


John J. Kasianowicz, Project Leader


Jessica Benjamini
Jacob Forstater
Haiyan Wang


John Kasianowicz

Joseph Robertson

Arvind Balijepalli

100 Bureau Drive, M/S 8120
Gaithersburg, MD 20899-8120