You are here

Allosteric Drug Discovery using Quantum Cascade Laser based Anisotropic THz Microscope (QCL-ATM)

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41GM140587-01A1
Agency Tracking Number: R41GM140587
Amount: $256,580.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: 400
Solicitation Number: PA20-265
Solicitation Year: 2020
Award Year: 2021
Award Start Date (Proposal Award Date): 2021-08-01
Award End Date (Contract End Date): 2022-07-31
Small Business Information
Mountain View, CA 94043-1996
United States
DUNS: 831746628
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: Yes
Principal Investigator
 (617) 399-6405
Business Contact
Phone: (617) 399-6405
Research Institution
AMHERST, NY 14228-2567
United States

 Nonprofit College or University

Allosteric Drug Discovery using Quantum Cascade Laserbased Anisotropic THz Microscope (QCL-ATM)
Proposal in Response to NIH/NIGMS STTR PA-20-265
This STTR will result in a commercially viable instrument that will enable critical research in allosteric drugs
and protein dynamics. To date allosteric inhibitors are largely found serendipitously. Anisotropic THz
microspectroscopy (ATM) uniquely measures the long range structural vibrations which serve as a mechanism
for allosteric control. ATM provides a tagless means to experimentally determine allosteric target sites. There
are NO commercial methods that provide this information currently. ATM systems used to establish the
technique are not accessible to a standard biochemical lab. In this STTR we will develop a compact system for
turnkey operation by academic and industrial researchers. This will be achieved by a collaboration of optical
engineers and biological physicists with unique expertise required. The system requires 1) high power tunable
THz source; 2) THz optical system for micro spectroscopy with polarization control; 3) high sensitivity room
temperature detection integrated into the microspectroscopy system; and 4) easy user interface. The
LongWave Photonics group has innovated high power compact THz sources (quantum cascade lasers, QCL’s)
and turn-key measurement systems based on these sources. The Markelz group at UB has innovated ATM. The
system, QCL-ATM, will be a turnkey tabletop instrument. In phase I the QCL-ATM will be developed to directly
probe vibrations within molecular standards (e.g. sucrose, fructose, and glucose and the protein crystal
tetragonal lysozyme) using polarized THz radiation within the 1.6 – 4.3 THz range of our QCL source and
measure the change in absorbance as the relative orientation of the crystal molecular samples and polarization
axis is varied. Using this demonstration of an integrated QCL-ATM instrument, we will identify the optical and
mechanical tolerances associated with the need to place both the sample and the detector entirely within the
near-field region of a focused THz beam as preparation for Phase II which will include measurement of the
effect of allosteric drugs on protein vibrations and the development of an automated polarization control
module and automated multi-sample platen with repeatable high-precision sample alignment to the
interrogating THz beam. The specific aims for Phase I are:
Aim 1. Construct and Characterize throughput QCL-ATM Microscope in the Far-field.
Aim 2. Characterize anisotropic absorbance with the QCL-ATM for molecular crystal standards.
Aim 3. Integrate near field pyroelectric detection into the QCL-ATM prototype and establish equivalence to
existing systems by measuring spectra of protein crystalAllosteric Drug Discovery using Quantum Cascade Laserbased Anisotropic THz Microscope (QCL-ATM)
Proposal in Response to NIH/NIGMS STTR PA-20-265
We propose to develop a benchtop spectroscopic system for rapid characterization of protein structural
dynamics based on terahertz polarimetric spectroscopy (anisotropic terahertz microscopy, or ATM). The
unique capability of this system to reveal previously unattainable information builds on the proposer’s
previous work by incorporating the recently developed high-power tunable terahertz source: the terahertz
quantum cascade laser (QCL). This lower complexity system will enable more researchers to perform studies
for the development of allosteric drugs, as well as increase the understanding of the impact of remote small
molecule binding and mutation.

* Information listed above is at the time of submission. *

US Flag An Official Website of the United States Government