SBIR-STTR Award

Laser Diode for Ion Channel Stimulation
Award last edited on: 2/6/09

Sponsored Program
SBIR
Awarding Agency
NIH : NINDS
Total Award Amount
$1,116,821
Award Phase
2
Solicitation Topic Code
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Principal Investigator
Mikhail I Nemenov

Company Information

Lasmed LLC

137 Irene Court
Mountain View, CA 94043
   (650) 965-8230
   info@lasmed-online.com
   www.lasmed-online.com
Location: Single
Congr. District: 18
County: Santa Clara

Phase I

Contract Number: 1R43NS046951-01
Start Date: 00/00/00    Completed: 00/00/00
Phase I year
2003
Phase I Amount
$100,000
The goal of this Phase 1 SBIR is to design and test a prototype of the Channel Laser Stimulator capable of stimulating single cells or part of the cell. This tool is needed to study dose dependency of heat/capsaicin-sensitive cells/neurons and "calcium" channels. Understanding how these "calcium" channels work and principles of their kinetics is important in neuroscience in general and especially in therapeutics and drug development. Further, the development of this instrument will enable the manipulation of cell activity in culture or in tissues with light, a method that could lead to important new applications for regulating cellular or physiological processes in vivo. This device may also lead to novel methods of drug screening and development as it could provide a rapid, well calibrated, and reproducible method of delivering a thermal pulse to cells or purified ion channel protein in single or multi-well format. We will design and test a Channel Laser Stimulator that (A) will deliver a consistent light intensity directly to the target-membrane and channels of the cell; (B) will enable the operator to precisely control the heat stimulus and thus activate some (predictable) amount of channel activity; and (C) will enable the operator to calibrate heat stimulus by power and pulse duration of the laser pulses. We will design this prototype of the Channel Laser Stimulator with parameters optimized for single cell level research, based on (1) the design of an infrared laser diode pain stimulator, developed by LASMED, and (2) the results of preliminary testing. We will consult with a leading scientist in the field of molecular investigations of thermo sensitive ion channels in the mammalian nervous system. All necessary tests to verify performance of the Channel Laser Stimulator will be carried out in the laboratory of this scientist by his personnel.

Thesaurus Terms:
biomedical equipment development, laser, membrane channel cell membrane, heat stimulus, light intensity, single cell analysis bioengineering /biomedical engineering

Phase II

Contract Number: 2R44NS046951-02
Start Date: 00/00/00    Completed: 00/00/00
Phase II year
2007
(last award dollars: 2008)
Phase II Amount
$1,016,821

The goal of this Phase II SBIR project is to develop and validate a laser diode stimulator to assess heat-sensitive Transient Receptor Potential (TRP) ion channels for in vitro and in vivo studies, using patch clamp recording and calcium imaging and compound action potential recording, respectively. This laser will be very useful for new drug discovery and evaluation, as there is currently no commercially available tool of similar capabilities. Evaluation of TRP family proteins can be useful in describing the potential utility of putative analgesic drugs. The ability to selectively (by temperature thresholds), reliably and reproducibly activate TRPs may also provide unique utility in understanding the mechanisms of antagonist action (binding) and provide additional information about mechanisms of interaction of different TRP proteins in cells and nerve tissue. There is also a potential utility of being able to differentially evaluate pain mediated by TRPV1 or TRPV2 proteins in the diagnosis and monitoring of progression of pain patients. Thus, it is our overall goal to establish stimulation protocols for use with a laser stimulator for in vitro and in vivo activation of heat gated ion channels. Laser stimulation is used for selective activation of C and A delta fibers in humans and rats (in our parallel projects), allowing reproducible protocols to test putative analgesic, from cell culture to humans. Thus, we hypothesize that the laser ion channel stimulator will prove safe and reliable action and will meet the FDA requirements for a laser device. To do this, we will develop an additional electronic circuit that allows the blockade of laser emission through the microscope, protecting eyes from any damage. We will also submit the laser and its components for certification of electrical and magnetic interference standards, and make any device changes that are necessary to meet the requirements. In addition, we will develop a protocol of direct temperature measurement of laser-induced temperature and modify the device to allow a tunable rate of heating. We will also insure the compatibility of the laser with calcium imaging and will continue to test the laser with TRPV1 DRG and HEK293 cells in order to study sensitization/desensitization processes. To do this we will apply brief and prolonged laser pulses and capsazepine. We will test the concept of TRP-associated activation of C and A delta fibers by direct laser activation of nerve fibers and application of the TRPV1 and TRPV2 antagonists capsazepine and ruthenium red. In vitro and in vivo protocols of non-invasive repeatable and reproducible activation of heat gated ion channels (TRP) can be useful tool for discovery and developing of analgesics. The ability to reliably, activate TRPV1/TRPV2 proteins in cell cultures and in tissue (in vivo) may also provide more accurate prediction of the efficacy of pain treatments based on TRP's antagonists. The brief heating allow investigating of molecular bases of activation of heat gated ion channels. There is currently no commercially available tool of similar capabilities on the market