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Microfluidic CAR-T Cell Processing Device

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 4R42CA228616-02
Agency Tracking Number: R42CA228616
Amount: $1,837,939.00
Phase: Phase II
Program: STTR
Solicitation Topic Code: 101
Solicitation Number: PA17-303
Solicitation Year: 2017
Award Year: 2019
Award Start Date (Proposal Award Date): 2019-06-01
Award End Date (Contract End Date): 2021-05-31
Small Business Information
Richmond, VA 23219-1551
United States
DUNS: 832526581
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (858) 353-4516
Business Contact
Phone: (858) 353-4516
Research Institution
87 Prospect Avenue - 2nd floor
United States

 Nonprofit College or University

The goal of this Fast-Track STTR project is to develop a Deterministic Lateral Displacement (DLD)
microfluidic device that can enrich white blood cells (WBCs) from a typical leukapheresis unit in 1 hr,
for use in manufacturing cancer cellular immunotherapy. Chimeric antigen receptor T cell (CAR-T) therapy
has been recommended for FDA approval to treat relapsed or refractory pediatric and young adult patients with
B-cell acute lymphoblastic leukemia. There is a critical need for cost-effective automated methods to improve
the efficiency and yield of large-scale enrichment of WBCs for use in manufacturing CAR-T and other cellular
GPB is a pioneer in developing novel DLD microchips to process blood cells for cell analysis (19,26). GPB now
proposes to develop, evaluate and commercialize a compact device in which an entire leukapheresis unit (up
to 5x1010 WBCs in up to 300 ml) can be processed in a “Leuko-stack” of disposable single-use multi-channel
DLD chips to produce in 1 hr a washed cell suspension that is enriched in WBCs and depleted of red blood
cells (RBCs) and platelets (PLT).
In Phase I, Aim 1 is to increase cell throughput through the current prototype chips by: 1) optimizing DLD chip
design and operation to increase flow rate; 2) increasing throughput by stacking plastic chips and running them
in parallel (“Leuko-stacks”); and 3) translating chip production to high-volume manufacturing material such as
Cyclic Olefin Polymer (COP). Final Phase I milestones to proceed to Phase II are: 1) final chip design with a
flow rate of at least 25 mL/hr via a single chip, at least 70% recovery of viable WBCs and immunophenotype-
defined T-lymphocytes, and ability to process cells for 1 hr without clogging; 2) Leuko-stack of at least 6 chips
run in parallel, with the same output as in #1; 3) combined increases in throughput via #1 and #2 sufficient to
process a 300 ml leukapheresis unit in 1 hr; 4) confirmation that the chips can be produced from COP.
In Phase II, Aim 2 is to build final prototype COP plastic chip-based microfluidic device capable of processing a
leukapheresis sample at 300 mL/hr. Aim 3 is to test performance of prototypes from Aim 2 with leukapheresis
aliquots and then full-size human leukapheresis samples. The final milestone of this project is to produce a
set of commercial prototype Leuko-stacks that can process an entire 300-ml leukapheresis unit in 1 hr
with at least 70% WBC and T-lymphocyte recovery, at least 90% depletion of RBCs, at least 80%
depletion of PLTs, and at least 70% recovery of T-cell expansion capacity (as compared with the input
samples) in significantly more than 50% of samples tested at 2 sites.
The GPB Leuko-stack platform will preserve the advantages of DLD microfluidic cell processing over current
methods, while massively increasing throughput rate and cell processing capacity, thus transitioning from
analytic- to preparative-scale WBC enrichment for subsequent manufacture of CAR-T and other cell therapies.PROJECT NARRATIVE
Targeted cellular immunotherapies for several hematologic malignancies, and potentially for solid cancers, are
nearly at hand. In order to increase their availability, there is a critical need for better methods to efficiently and
cost-effectively isolate large quantities of the white blood cells needed to manufacture the therapeutic cells in
sufficient quantities. This project proposes to scale up a proprietary microfluidic cell processing technology to
enrich white blood cells from leukapheresis harvests, the first step in engineering/manufacture of therapeutic
chimeric antigen receptor T cells (CAR-T) that can cure leukemias and other cancers. Successful completion
of this work will result in a well-characterized prototype for a white blood cell enrichment device that will be
ready for product development and extensive testing and suitable to meet regulatory approval standards.

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

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