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Microfluidics Platform for Rapid, High-throughput Screening of Therapeutic Bacteriophages Based on Patient Bacterial Isolates

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R43GM146502-01
Agency Tracking Number: R43GM146502
Amount: $314,411.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: 400
Solicitation Number: PA21-259
Timeline
Solicitation Year: 2021
Award Year: 2022
Award Start Date (Proposal Award Date): 2022-04-15
Award End Date (Contract End Date): 2023-04-14
Small Business Information
1160 BATTERY STREET EAST, STE 100
San Francisco, CA 94111-1233
United States
DUNS: 117121584
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 ROBERT MCBRIDE
 (858) 366-2331
 rob@felixbt.com
Business Contact
 ROBERT MCBRIDE
Phone: (858) 366-2331
Email: rob@felixbt.com
Research Institution
N/A
Abstract

PROJECT SUMMARY—Felix Biotechnology is developing a microfluidics platform for rapid, high-throughput
screening of therapeutic bacteriophages that target disease-causing bacteria. Federal agencies, multiple
companies, and infectious disease specialists in major academic medical centers across the US are advancing
the use of phages for a broad range of applications including the treatment of multi-drug resistant bacterial
infections and the prevention of food-borne illnesses. While these efforts show great promise, the narrow host
range of most phages limits the commercial and clinical potential of phages as a generalized tool. Engineering
phage with expanded host ranges may provide a possible solution, but researchers lack the necessary
understanding of the genetic factors that determine host range. Collecting data on genetic variation in host range
is time consuming, expensive, and low throughput. In preliminary studies, Felix demonstrated 1) the ability to
reliably combine bacteria and phage in reproducible ratios in single droplets using a co-flow focusing device, 2)
the ability to co-culture bacteria and phage in the droplets and observe phage-specific killing of target bacteria,
and 3) the ability to optimize the ratio of bacteria to phage to achieve ≥ 99.9% killing in susceptible strains. In
this proof-of-concept Phase I SBIR, Felix proposes to tag phages and bacteria with unique oligonucleotide-based
barcodes prior to combining them in droplets, sort droplets where phage successfully kills the bacteria, unify the
respective barcodes (“epicPCR”) by merging droplets where phage kill bacteria with PCR reagents and then
fusing the barcodes identifying the specific phage and specific bacteria that were involved. The droplets would
then be lysed and the pool of hybrid barcodes would be sequenced, giving us information on and sequence-
unified amplicons for detecting a lytic pairing. Felix will then demonstrate the ability to distinguish correctly paired
phage/bacteria in a 10 x 10 matrix of different phages and bacteria. Aim 1. Validate the use of oligonucleotide
barcodes for identifying phage/bacteria pairing in droplets. Milestone / Success Metric: Validation of 20 unique
oligonucleotide-based barcodes (10 phage, 10 bacteria). Aim 2. Demonstrate the ability of barcodes to correctly
identify phage/bacteria pairs when starting with a matrix of 10 different phages and 10 different bacteria.
Milestone / Success Metric: ≥ 80% agreement between traditional plaquing assay and the microfluidics assay.
Go/No-Go Criterion for Advancing to Phase II: At least 80% agreement between plaquing and microfluidics
assays for identifying phage/host pairs is sufficient to warrant further optimization. Impact—Successful proof-of-
concept would support further development of a microfluidics device with a target product profile capable of
screening a matrix of 1,000 x 1,000 with ≥ 95% agreement with traditional plaquing assays. This would provide
orders of magnitude more data than current methods, providing the volume of data needed to accurately identify
the genetic basis of host range and engineer phages with expanded host range. These advances could
accelerate the use of phages as a sustainable first-line treatment for bacterial disease.

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

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