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MDS
Sciex’s Cellular Dielectric Spectroscopy CellKey
System
Pharma DD
spoke to Anna Aherne, Senior Product Manager, MDS
Sciex, and Paul Dovile, Manager, Life Sciences
Instrument Design and Development, Invetech.
Pharma DD: Describe the CellKey system.
Dr.
Aherne: The
CellKey system offers a complete solution for
evaluating receptor function in live cells. It enables
label-free, real-time analysis of endogenous
cell-surface receptor activity in a single-assay
format. The product includes an instrument component
(developed by Invetech, based on an MDS Sciex
concept), as well as a custom consumable, which is a
96-well microplate used during the assay. This custom
microplate has electrodes at the bottom of each of the
96 wells allowing for impedance measurements. Tying it
all together is a software analysis program, which
basically controls all aspects of the CellKey system,
from set up of the assay protocol and running of the
assay, to collection and analysis of data. The CellKey
platform is based on Cellular Dielectric Spectroscopy
(CDS) technology.
Pharma DD:
What is CDS?
Dr.
Aherne: CDS is
a label-free, cell-based technology based on the
measurement of complex impedance changes. Impedance is
related to the ratio of voltage to current as
described by Ohm’s law. Cells are seeded onto the
CellKey system’s custom 96-well microplate, which
contains electrodes at the bottoms of the wells. CDS
measures changes in impedance upon stimulation of
different cell-surface receptors. These impedance
measurements of cellular response are used to provide
high levels of information on the consequences of
activating a cell-surface receptor in a simplified,
label-free, non-invasive manner.
To
measure impedance changes in cells of interest, as I
just mentioned, the cells are seeded onto the custom
96-well microplate containing the electrodes. The
CellKey system then supplies constant voltage, across
a range of frequencies, producing a low-frequency
current, which flows between the cells (extracellular
current), and a higher-frequency current which flows
through the cells (transcellular current).
Contributors to impedance measurements include changes
in how cells adhere to those custom plates (i.e.
substrate), changes in the shape or volume of the
cell, and changes in the cell-cell interactions
following activation of the receptor. Individually or
collectively, these changes affect the flow of
extracellular and transcellular currents and influence
the magnitude and characteristics of the signal or
impedance measured. The characteristics of the
impedance measurements we make are indicative of the
signaling pathways that are activated via receptor
stimulation.
Pharma DD:
Who was the CellKey system developed for?
Dr.
Aherne: The
CellKey system was designed to meet the needs of drug
discovery scientists who are typically involved in
target identification, target validation, secondary
screening, and lead optimization. The system was
launched in September 2005, and we have been extremely
pleased so far with its adoption rate, as well as the
excitement the CellKey system has generated within the
industry. While it is not our policy to reveal the
names of our customers, many podium presentations and
posters referencing the CellKey system have been
presented by users over the last year and will be
available on our new Web site that will be launched
soon. Readers can contact us for copies of these in
the meantime.
Pharma DD:
What are the CellKey system’s unique advantages vis-à-vis
its competitors?
Dr.
Aherne: We sell
into a highly competitive space, which includes the
whole range of technologies targeted toward drug
discovery, encompassing target identification through
lead optimization. We’re in a space between
high-throughput screening technologies, for example
MDC’s FLIPR products, and high-content screening
technologies such as Cellomics’ ArrayScan. We see
ourselves as being in the middle and complementary to
those two extremes.
The
market for label-free technology is certainly taking
off. A number of label-free technologies have emerged
in recent years. I think this increased interest is a
testament to the fact that label-free technologies
offer a number of key advantages over some of the
existing technologies.
The CellKey system measures activation of
endogenous receptors in their native cellular
environments to generate more bio-relevant data.
Data is more bio-relevant, owing to the CellKey
system’s non-invasive, label-free technology.
Traditionally when we talk about cell-based assays we
think of using cells which have undergone either
genetic or chemical manipulation in order to over
express the receptor of interest or express some
fluorescent label. That manipulation changes not only
the characteristics of the cells, but also the
characteristics of the receptor target of interest. So
it keeps raising the question, are those leads
obtained via traditional cell-based assays, which have
been subjected to such manipulation, good-quality
leads—do they stand a chance of success in clinical
trials? Certainly the last ten years have shown that
despite the quantity of leads coming out of primary
screening, we’re not seeing an appropriate,
corresponding number of new drugs reaching the market.
That
is the CellKey system’s top advantage: It allows the
study of endogenous receptors—that is, receptors
expressed at normal levels in the cells where they
would typically be expressed. Because it does not
involve any genetic or chemical manipulation of the
cells, the CellKey assay gathers data that are more
physiologically relevant and representative of the
receptor target’s true native environment.
At
the recent Society of Biomolecular Sciences
conference, a presenter from Boehringer Ingelheim
talked about their experience using the CellKey
system. In that presentation, it was mentioned that
the data collected using the CellKey system (on a GPCR
target) matched the data obtained using an animal
model. Notably, this was not the case when using some
of the other in
vitro assays. Again, I think this example
illustrates the power and advantages of being able to
study the receptor system endogenously.
The label-free feature is highly appealing
to today’s drug discovery researchers.
It removes the time-consuming and often costly step of
trying to optimize the assay using labels. One
customer using the CellKey technology reports they
have reduced the length of their assay development
process from months to weeks.
A
label-free assay also minimizes the risk of picking up
interference or artifacts in the data. All of these
factors suggest that the CellKey platform can help
bring the real biology back into drug discovery, and
has the potential to reveal compounds that are
different than those obtained from the more artificial
systems scientists have become accustomed to using
over the last couple of decades.
The
CellKey system’s label-free nature also means it is
a universal platform. So regardless of the receptor
under study, regardless of its coupling mechanism, we
can use a single-assay format to study various kinds
of receptors, such as GPCRs or tyrosine kinase
receptors, without having to significantly modify the
assay format.
Pharma DD:
Will there be further development of the CellKey
system, or any refinements made to it, based on your
customers’ feedback?
Dr.
Aherne: We
involved prospective customers to a large extent in
the development of the CellKey platform. Part of our
business model was to ensure that we were developing a
product that customers would really want at the end of
the day. We went to industry and talked to key members
of the drug discovery community to find out which
features we should include in the CellKey system, how
we should develop the software to match typical
workflow, et cetera. Now that we have built up
relationships with customers, we are continually
listening to and actively seeking their feedback on
potential improvements to make to the existing
platform, and what to include in next-generation
products. The CellKey system is intended to be one in
a series of products geared toward the cell-based
assay marketplace. We are currently lining up projects
that are intended to enhance the capabilities and
applications of the existing system, and we’re also
planning to launch future generations of the CellKey
platform.
MDS
Sciex commissioned Invetech
to develop the instrument component of the CellKey
System.
Pharma DD:
Why did you choose Invetech to develop the CellKey
instrumentation?
Dr.
Aherne:
Invetech possessed the skill sets we needed to develop
the various components of the CellKey system. We also
liked their business model, their wide-ranging
capabilities, and the interactions we had with them.
Pharma DD:
Did you look at companies besides Invetech to develop
the instrument component?
Dr.
Aherne: We did
our due diligence, evaluating companies that would be
able to operate on a global sense, because MDS Sciex
operates on a global basis. We made the decision based
on who we felt could best deliver the products and
components that we needed in the timeframe given, and
Invetech matched those expectations.
Pharma DD:
Does the CellKey product represent the first
collaboration MDS Sciex has had with Invetech?
Dr.
Aherne: Yes,
this was our first partnership with Invetech.
Pharma DD:
Briefly describe Invetech’s business model.
Mr.
Dovile: For
more than 20 years Invetech has been at the forefront
of new product development and automation. With
experience drawn from over 5,000 projects, we deliver
global contract design and development, contract
instrument manufacturing, and custom automation
services to life sciences, drug discovery, and
pharmaceutical companies. We work with seven of the
world’s top ten clinical diagnostic companies.
We
combine integrated in-house capabilities, specialist
knowledge, and diverse experience to deliver better
solutions, in the shortest possible time and with less
risk, to our client base of start-ups through to
multinationals. Our commercial focus, responsive and
flexible approach, and unbiased solutions mean our
clients get the best outcome with the aim of
commercial success.
Pharma DD:
Because your company developed CellKey’s instrument
component, is it proprietary to Invetech?
Mr.
Dovile:
According to our business model, Invetech does not
take any ownership of IP created under the assignment.
Whenever we work with a client on a development
project, all new IP is owned by the company we are
working for. Therefore, the CellKey instrument design
is wholly the property of MDS Sciex.
For
more on Invetech, visit http://www.invetech.com.au/.
Product:
Cellular Dielectric Spectroscopy CellKey System
Vendor: MDS Sciex
Available: Now
For more information: http://www.mdssciex.com
Copyright 2006, Cambridge
Healthtech Institute. All Rights Reserved.
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