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