MICROBRIGHTFIELD, LLC — Department of Health and Human Services SBIR Phase I: 101

Description

DESCRIPTION provided by applicant As a highly used model organism Caenorhabditis elegans C elegans worms offer a wide range of possibilities for scientific research With advantages including but not limited to easy maintenance and handling forward and reverse genetic manipulability and a fully mapped nervous system connectome of neurons C elegans offer a high throughput alternative to larger rodent model organisms During the last decades C elegans has become an indispensable tool for advanced research in the fields of aging neurodegeneration toxicology drug discovery and RNAi screening to mention only a few Attractive instruments for studying the function of C elegansandapos nervous system are i worm trackers i e software packages designed to quantify different aspects of C elegansandapos behavior ii monitoring neural activity using genetically encoded calcium indicators calcium imaging and iii manipulation of neural activity using optogenetics and femtosecond laser nanosurgery However because of technical shortcomings and lack of integration in their current form these instruments cannot be considered adequate for next generation research in various fields such as aging neurodegeneration toxicology drug discovery and RNAi screening applying C elegans In response to this challenge this project aims to develop an innovative microscope system for sophisticated investigations of C elegansandapos nervous system in action andquot Worm Investigatorandquot The Worm Investigator system will allow scientists for the first time to monito and manipulate the nervous system of a freely moving worm using calcium imaging optogenetics and femtosecond laser nanosurgery while simultaneously tracking and analyzing the wormandapos s complex behavior before during and after manipulation This new commercial system will be based on four distinct innovations to be developed as new embodiments of the following technology patented by MBF i a dual objective microscope setup ii two Worm Tracking Objective Lens tm WTOL devices iii a novel side ring LED illuminator patent application in preparation and iv our WormLab r worm tracking software The benefit for the research community and society in general will be progress in next generation research in the fields of aging neurodegeneration toxicology drug discovery and RNAi screening applying C elegans This will result in the ability to make new discoveries based on new studies that are currently not feasible which may ultimately provide the basis for novel treatment strategies for a wide variety of diseases During Phase I we will develop a prototype dual WTOL further develop a novel side ring LED illuminator part of our pre existing technology and develop a calibration test slide serving the specific needs of the Worm Investigator dual WTOL microscope as well as software to simultaneously move two WTOL devices and acquire synchronized images from each camera of the dual WTOL microscope PUBLIC HEALTH RELEVANCE This project will create an innovative microscope system for integrated advanced tracking and analysis of complex behavior with simultaneous manipulation and monitoring of neural activity in freely moving C elegans worms This system will enable next generation research in various fields such as aging neurodegeneration toxicology drug discovery and RNAi screening for which C elegans has emerged as a powerful research tool The benefit for the research community and society in general will be the ability to conduct innovative studies applying C elegans that are currently not feasible and thereby enable new discoveries that may ultimately provide the basis for developing novel treatment strategies for a wide variety of diseases