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Enabling point of care molecular diagnostics by developing an adaptive PCR instrument and on demand kit reagents

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R42HG009470-01A1
Agency Tracking Number: R42HG009470
Amount: $287,251.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: 172
Solicitation Number: PA16-303
Solicitation Year: 2016
Award Year: 2017
Award Start Date (Proposal Award Date): 2017-04-01
Award End Date (Contract End Date): 2017-08-31
Small Business Information
Murfreesboro, TN 37130-6939
United States
DUNS: 185656402
HUBZone Owned: No
Woman Owned: Yes
Socially and Economically Disadvantaged: No
Principal Investigator
 (615) 896-7353
Business Contact
Phone: (615) 896-7353
Research Institution
NASHVILLE, TN 37240-7749
United States

 Nonprofit College or University

Because of its high sensitivity polymerase chain reaction PCR is the gold standard for the diagnosis
of many infectious diseases but generally only implemented in well equipped laboratories One of the major
roadblocks for expanding PCR to point of care markets is the lack of simple robust single tube PCR designs
which preserve its laboratory based high sensitivity and specificity In this Fast Track STTR application
BioVentures Inc and Vanderbilt University a nearby research institution propose to develop a fundamentally
different PCR design hybridization triggered PCR HT PCR It alters the way PCR cyclic amplification is
monitored and controlled resulting in a design more suitable for underserved point of care markets The HT
PCR technology co invented by the applicants meshes well with BioVenturesandapos s successful business model of
manufacturing and selling molecular biology reagents and aligns with its strategy to expand into the clinical
diagnostic market Phase I and II Aims evaluate the feasibility and advantages of this approach with studies to
detect DNA biomarkers of three major infectious diseases
One of the major impediments to simple robust single tube PCR is that an efficient amplification
reaction requires a narrow range of thermal and chemical conditions Point of care settings including walk in
clinics rural health outposts and outbreak surveillance by mobile response units generally lack the stringent
sample preparation and controlled environmental requirements available in centralized laboratories The
fundamental limitation with all current PCR designs is that thermal cycling is controlled by pre determined
indirect temperature measurements yet the PCR product melting step and more importantly the primer
annealing step do not always occur at the programmed temperatures Individual reaction conditions ambient
temperatures and thermal calibrations create disparities between the expected hybridization state of the
product or primers and the actual hybridization state These disparities are exacerbated in diagnostic settings
that are less equipped to precisely control environmental conditions and sample contents leading to PCR
failure i e false negatives We propose an alternative PCR design that dynamically controls thermal cycling
by optically sensing the annealing and melting of mirror image L DNA surrogates of the reactionandapos s primers and
targets Because the properties L DNA enantiomers parallel those of natural D DNAs the L DNA reagents are
used to indicate the cycling conditions required for effective primer annealing and product melting during each
cycle without interfering with the reaction A major advantage of this approach is that it enables hybridization
triggered heating and cooling without the need to know reaction temperatures and times Thus the instrument
dynamically adapts to unpredictable thermal and chemical variations A second major advantage is that the L
DNA surrogates of the PCR product can also be used as controls for reagent rehydration sample preparation
instrument performance diagnostic threshold and correct product formation enabling well controlled single
tube analysis of DNA Project Narrative
Because of its high sensitivity polymerase chain reaction PCR is the gold standard for the molecular
diagnosis of many infectious diseases but only in well equipped diagnostic facilities One of the major
impediments to the expansion of PCR to point of care markets is the lack of a simple and robust
implementations of PCR In this application we propose to develop PCR reaction additives and simplified
instrumentation that enable single tube diagnostics more suitable for underserved point of care markets

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

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