Biomedical Engineering Reference
In-Depth Information
the development of POC testing that include reduced costs, timely test results, lower
mortality rates, and reduced morbidity.
Today's flow cytometers are sophisticated analytical instruments that are exten-
sively used in research and clinical laboratories. Their complex measurement
principles make it challenging to package such a system into a mechanically
rugged, compact, low-power, and inexpensive instrument. However, for the clearly
defined use of CD4 and CD4% testing, such an instrument is now commercially
available (Partec, CyFlow miniPOC), and we are certain that similar devices for
other applications will follow. The applicability of a flow cytometer in the field will
be evaluated, and this device and others will be continuously improved based on
field experiences.
In particular, the cost of devices and the cost per test will be a driver for
further development for any POC testing device. Smaller sizes, more functionality,
better accuracy, etc., will be naturally included in the next generation of these
devices. Blood glucose meters for diabetics are probably the best example for this
development outline. Today, however, no POC flow cytometer has a maturity that is
comparable to any given blood glucose meter.
The technical challenges for a POC flow cytometer can be grouped into two sets
of problems - fluidic handling and optical detection.
Most advanced POC devices will require sample preparation steps. Sample
preparation represents a major source of errors, in particular if performed by
minimally trained operators. Skilled operators on the other hand are a significant
cost factor in testing, but they still do not guarantee error-free operation. Therefore,
automatic sample acquisition and preparation of minimal amounts is a benefit
for any biomedical POC (or conventional) testing device. Numerous microfluidic
and fluidic chip-based sample handling approaches have been presented and
implemented: on-chip cell lysing, microfluidic separation of white blood cells, and
automated specific staining of cells only to name a few.
The basis for on-chip sample preparation is in most cases reliable fluidic han-
dling. This includes actuating, valving, mixing, and metering nano- to microliters
of various liquids. To avoid large external pumps, the need for pressure lines, and
complex pressure interfacing with a fluidic chip, which would contradict the idea of
a portable POC devices, on-chip fluid handling has been developed. An impressive
toolbox of fluid handling techniques has been developed, many different complete
fluidic solutions have been demonstrated, and the field is still rapidly progressing.
At PARC, we have mainly focused on demonstrating and benchmarking a new
optical detection technique that meets the requirements of POC devices. “Spa-
tially modulated fluorescence emission” delivers high signal-to-noise discrimination
without precision optics to enable robustness, compactness, and low cost in POC
flow cytometers. The design is based on a large-area optical encoding-decoding
mechanism rather than a redesign of a classical flow cytometer.
Our detection technique generates a time-dependent signal as a continuously
fluorescing bioparticle traverses a predefined pattern for optical transmission.
Correlating the detected signal with the known pattern achieves high discrimination
of the particle signal from background noise.
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