Flow Cytometry on a Chip - Point-of-Care Diagnostics on a Chip - page 47

Microflow cytometers are being developed and tested in many labs for various
applications, including blood analysis [ 23 ], CD4 counting [ 13 ], multiplexed bead
assays [ 24 ], and ocean water monitoring [ 25 , 26 ]. A group at NRL has demonstrated
simultaneous diagnosis of 12 different infectious diseases in serum [ 24 ]using
bead-based assays and is currently integrating on-chip sample processing for
POC use as a 30-min test. This group is also testing their microflow cytometer
for real-time measurements of marine phytoplankton populations based on size
and intrinsic fluorescence from chlorophyll and other light-harvesting pigments
[ 25 , 26 ]. This group claims that unlike most other microflow cytometers, their
system can analyze cells ranging in size from 1 to over 100m. Researchers at
Los Alamos National Laboratory have tested and evaluated very inexpensive lasers
[ 27 ] and data systems [ 28 ]. Their goal is to reduce the cost of conventional flow
cytometry and make them more widely available for point-of-care applications.
A group at Purdue University is developing a LED-based microfluidic cytometer
with integrated sample preparation. They have demonstrated the feasibility of using
magnetic nanoparticles for on-chip sorting of human white blood cells from red
blood cells and subsequent analysis of white blood cell subsets using antibody-
labeled quantum dots [ 23 ]. This work as well as many other activities on this field
is driven by the vision to develop an integrated handheld, portable, battery-powered
unit for rapid blood analysis from a single drop of whole blood that is completely
processed on-chip.
To date no flow cytometer meets all technical requirements for POC detection; in
particular, the cost target remains extremely challenging. However, there are many
interesting concepts under development. Especially the ones based on microfluidic
flow cells look very promising. Based on the recent progress in this field, one can
be cautiously optimistic that low-cost microcytometers for POC diagnostics will be
available soon.

3.2 On-the-Flow Analyte Characterization Based on Spatial

Modulation Technique

3.2.1 Spatially Modulated Fluorescence Emission:

The Enabling Technique

PARC has demonstrated a new optical detection technique that delivers high
signal-to-noise discrimination without precision optics to enable an optofluidic
detector that can combine high performance, robustness, compactness, low cost,
and ease of use. Detection sensitivity and analyte throughput can meet or even
exceed the specifications of currently available (commercial) high-performance flow
cytometers with the addition of point-of-need compatibility.
The enabling technique is termed “spatially modulated emission” and generates
a time-dependent signal as a continuously fluorescing (bio-)particle traverses a