Digitizing Biology: The Roswell Molecular Electronics Platform for Biosensing - 13

EXPERT PANEL DISCUSSION
of proteins. As mentioned before, there is a need to
validate some of the most used antibody-based testing
so that we can bring forth a single test on a single
platform that covers, for example, a diabetic monitoring
test or an annual preventative care test. I am
interested in seeing how proteins and antibodies can
be developed on this platform. The platform now
exists, and the article shows proof of concept, but
there is scientific work that remains to be done, such
as validation experiments and content loading, to
create a critical mass so that we can use this chip
clinically.
Dr. Fuller: The technology also does not require large
hardware. Does that mean that we could bring the
testing closer to the patient? The hardware needed to
run the chips seems to fit well with those kinds of uses.
I think it will be an interesting challenge to see where it
can advance medical practice in the future.
Dr. Moarefian: I am interested in seeing more expansion
on sequencing. If we can see the interaction of
RNA and single-stranded DNA with proteins to get the
sequence, I would be interested in that application.
Dr. Fuller: Sequencing is certainly one of our major
areas of development. There are definitely exciting
possibilities there, and not
only for long rapid reads
on small devices, or for
massive throughput on
high-pixel count chips.
Other exciting things enabled
by our new sensor
and measurement include
direct sequencing of fulllength
RNA, or direct
reading of methylation or
other epigenetic marks, as well as fundamental studies
of polymerase enzyme kinetics and the engineering of
new enzymes with desirable features.
''
Dr. Frost: My first love is fuel-driven molecular
machines. How do macromolecular complexes burn
chemical energy to perform work? Anything that can
be done to push forward that ambition is the top of my
priority list. After the polymerases, the ribosome is the
top of my list as far as the next molecular machine to
probe with the Roswell technology. In the diagnostic
space, a chip that is adequately multiplexed on a single
experiment to provide diagnostic information for what
is present in a complex sample, such as a nasal swab
from a patient with an unknown virus, would also be
enormously impactful in the near term.
I am curious to hear more from Carl about how the
full power of unlabeled analysis can be coupled with
ª 2022 Mary Ann Liebert, Inc.
analyzing specific molecular labels. I think that is very
much a future opportunity for Roswell.
Dr. Fuller: We have done what I call ''stacked up''
assays, in which we take monoclonal antibodies with
His tags and use these to attach them to our bridge with
an anti-His tag aptamer on the chip, and then we can
use this sensor to look at further binding of the antibody's
target. In some ways, in this approach we have
already used a label in conjunction with binding on the
chips and it has worked quite effectively. There will be
many other opportunities because His tags and other
epitope tags are universally used for a lot of protein
engineering work, and it will be a good addition to our
toolkit to use these types of labels to wire molecules
into our chip.
Dr. Lin: After reading the PNAS article, what aspect
of the science behind the Roswell molecular
electronics chip did you find the most exciting?
Dr. Wohlgemuth:
The magic here is on the chip fabrication. This chip
The magic here is on the chip
fabrication. This chip can reduce
the human capital needed to run
assays, which is a big deal in the lab
industry.'' - Jay Wohlgemuth
can reduce the human capital needed to run assays,
which is a big deal in the lab industry. We do not have
enough people to run assays, and this chip could enable
work to be done in a highly automated manner
without a lot of human
capital. In addition, it is
environmentally friendly.
We are not using additional
reagents. We have
an instrument the size of a
laptop so that we are not
generating a bunch of
fluorescent or radioactive
waste. This chip could
solve several issues that
are inefficiencies in the laboratory industry.
I am struck that this platform has so many different
applications. I think Roswell has some prioritization
decisions on its hands regarding what is going to move
the needle next. How do we get the chip into the drug
development and research space where there are immediate
applications? Where can this chip add value to
clinical diagnostics in the next 5 years? It is a challenge
because we potentially could measure every type
of analyte and sample, but there is a lot of work to
figure out the next move to develop this platform for
clinical diagnostic use, where it has tremendous
promise.
Dr. Frost:
What excites me about the Roswell chip is that it
opens a new window into molecular interactions that
allow for single-molecule detection of millisecond
5
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