Advancing Single Molecule Sensors - Platforms to measure single molecular-binding, -folding and -motion towards unlabeled molecule detection
Dr. Jakob Buchheim
Bioelectronics Systems Lab, Columbia University in the City of New York, USA
Common techniques for molecular detection and sequencing rely on large sample volume,
molecular purification and/or molecular amplification as well as labeling approaches in
order to identify individual most often predetermined compounds. The low sensitivity of
used detection technique requires these additional amplification steps to generate enough
‘signal’ to analyze. Consequently, these approaches lack the ability to resolve unexpected
compounds, molecular variations or to handle small sample quantities of highly variable
composition from for example a single cell.
In contrast, solid state nanopore (ssNP) sensors as well as single molecule field effect
transistors (smFET) both offer exceptional sensitivity towards single molecules presence.
Enabled by nanoscale engineered structure, they allow to obtain measurements stemming
from individual molecules which interact in a locally confined way with the device.
Measuring the device’s changing behavior allows to extract information about the
interacting molecule its nature and properties. Here, I present the recent advancement in
smFET and ssNP device platforms enabling new applications of unlabeled detection.
Specifically, I will present the analysis of single aptamer grafted smFET data for serotonin
binding, highlighting the unique ability of single molecular interaction to resolve aptamer
configurations. Further, I will show advancements of a ssNP sensor to a pore-cavity-pore
device allowing single molecule time-of-flight measurements of proteins giving access to
single molecule mobility measurements in solution.