Fast and efficient method to produce red blood cells developed
New technology cuts down on cell culture time by half and uses more
targeted cell sorting and purification methods

Date:
September 14, 2020
Source:
Singapore-MIT Alliance for Research and Technology (SMART)
Summary:
Researchers have developed a faster and more efficient way to
manufacture red blood cells that cuts down on cell culture time
by half. The cells are frozen in liquid nitrogen and thawed on
demand to produce matured RBCs in only 11 days, removing the
need for continuous 23-day manufacturing. The team also designed
complementary technology for more targeted cell sorting and
purification.



FULL STORY ========================================================================== Researchers from Singapore-MIT Alliance for Research and Technology
(SMART), MIT's research enterprise in Singapore, have discovered a new
way to manufacture human red blood cells (RBCs) that cuts the culture
time by half compared to existing methods and uses novel sorting and purification methods that are faster, more precise and less costly.


========================================================================== Blood transfusions save millions of lives every year, but over half
the world's countries do not have sufficient blood supply to meet
their needs. The ability to manufacture RBCs on demand, especially the universal donor blood (O+), would significantly benefit those in need
of transfusion for conditions like leukemia by circumventing the need
for large volume blood draws and difficult cell isolation processes.

Easier and faster manufacturing of RBCs would also have a significant
impact on blood banks worldwide and reduce dependence on donor blood
which has a higher risk of infection. It is also critical for disease
research such as malaria which affects over 220 million people annually,
and can even enable new and improved cell therapies.

However, manufacturing RBCs is time-consuming and creates undesirable
by- products, with current purification methods being costly and not
optimal for large scale therapeutic applications. SMART's researchers
have thus designed an optimised intermediary cryogenic storage protocol
that reduces the cell culture time to 11 days post-thaw, eliminating
the need for continuous 23-day blood manufacturing. This is aided by complementary technologies the team developed for highly efficient,
low-cost RBC purification and more targeted sorting.

In a paper titled "Microfluidic label-free bioprocessing of human
reticulocytes from erythroid culture" recently published in the journal
Lab on a Chip, the researchers explain the huge technical advancements
they have made towards improving RBC manufacturing. The study was carried
out by researchers from two of SMART's Interdisciplinary Research Groups
(IRGs) -- Antimicrobial Resistance (AMR) and Critical Analytics for Manufacturing Personalised-Medicine (CAMP) - - co-led by Principal Investigators Jongyoon Han, a Professor at MIT, and Peter Preiser,
a Professor at NTU. The team also included AMR and CAMP IRG faculty
appointed at the National University of Singapore (NUS) and Nanyang Technological University (NTU).

"Traditional methods for producing human RBCs usually require 23
days for the cells to grow, expand exponentially and finally mature
into RBCs," says Dr Kerwin Kwek, lead author of the paper and Senior Postdoctoral Associate at SMART CAMP. "Our optimised protocol stores
the cultured cells in liquid nitrogen on what would normally be Day 12
in the typical process, and upon demand thaws the cells and produces the
RBCs within 11 days." The researchers also developed novel purification
and sorting methods by modifying existing Dean Flow Fractionation (DFF)
and Deterministic Lateral Displacement (DLD); developing a trapezoidal cross-section design and microfluidic chip for DFF sorting, and a unique sorting system achieved with an inverse L-shape pillar structure for
DLD sorting.

SMART's new sorting and purification techniques using the modified DFF and
DLD methods leverage the RBC's size and deformability for purification
instead of spherical size. As most human cells are deformable, this
technique can have wide biological and clinical applications such as
cancer cell and immune cell sorting and diagnostics.

On testing the purified RBCs, they were found to retain their cellular functionality, as demonstrated by high malaria parasite infectivity
which requires highly pure and healthy cells for infection. This
confirms SMART's new RBC sorting and purifying technologies are ideal
for investigating malaria pathology.

Compared with conventional cell purification by fluorescence-activated
cell sorting (FACS), SMART's enhanced DFF and DLD methods offer comparable purity while processing at least twice as many cells per second at less
than a third of the cost. In scale-up manufacturing processes, DFF is
more optimal for its high volumetric throughput, whereas in cases where
cell purity is pivotal, DLD's high precision feature is most advantageous.

"Our novel sorting and purification methods result in significantly
faster cell processing time and can be easily integrated into current
cell manufacturing processes. The process also does not require a trained technician to perform sample handling procedures and is scalable for
industrial production," Dr Kwek continues.

The results of their research would give scientists faster access to
final cell products that are fully functional with high purity at a
reduced cost of production.


========================================================================== Story Source: Materials provided by Singapore-MIT_Alliance_for_Research_and_Technology_ (SMART). Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Kerwin Kwek Zeming, Yuko Sato, Lu Yin, Nai-Jia Huang, Lan Hiong
Wong,
Hooi Linn Loo, Ying Bena Lim, Chwee Teck Lim, Jianzhu Chen, Peter R.

Preiser, Jongyoon Han. Microfluidic label-free bioprocessing of
human reticulocytes from erythroid culture. Lab on a Chip, 2020;
DOI: 10.1039/ C9LC01128E ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200914095905.htm

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