Cell-Based Chips for Biotechnology - Introduction to BioMEMS - page 247

5
Cell-Based Chips for Biotechnology
The previous chapter dealt exclusively with microdevices that process cell-free
samples or cell extracts—in other words, the biological material was not alive , which simpli-
ies both its maintenance and its readout. A whole new set of challenges is presented to the
experimenter when the measurement or question requires that the interrogated sample be
kept alive, as we will see in the next three chapters. In this chapter, we will look at applications
that have traditionally concerned the biotechnology industry, that is, primarily with a health
care device focus.
5.1 Microluidic Flow Cytometers
Possibly the most basic operation one can do with cells is to count them. Flow cytometers are
devices that allow for counting particles (such as cells or beads) suspended in a stream of luid.
he device produces a stream (typically a single cell wide) carrying a cell suspension ensheathed
in a larger stream, which acts as a carrier that places the cells in line with the detector. Traditional
(nonmicrofabricated) low cytometers are expensive, bulky, and tedious to operate, hence great
research eforts have been deployed to miniaturize and automate low cytometry since the early
days of microluidics.
Michael Ramsey's group, from Oak Ridge National Laboratory in Tennessee, was the irst
to demonstrate in 1997 the two-dimensional coninement or “focusing” of low (of rhodamine
6G in Figure 5.1 ). he focusing is achieved by “pinching” the sample low between two focusing
lows; the width and position of the output focused low is a function of the focusing low rates
relative to that of the sample. he device was built in glass and the low was controlled electroki-
netically; however, the same functionality can be achieved in a much simpler setup with a PDMS
device and gravity-driven lows or syringe pumps.
However, achieving focus in two dimensions is generally not enough because of the “but-
terly efect” (see Section 3.9.1 and Figure 3.73 )—the particles that are traveling close to the
roof or the loor of the channel will be lowing much slower than the particles traveling close
to the midline of the channel, which will confound the detector. Ideally, a scheme that allows
for focusing in three dimensions (3-D), creating a single-cell-wide, constant-velocity stream in
the center of the channel, is desirable. Wanjun Wang's group at Louisiana Tech University used
sophisticated tilted photolithography to create a real microfabricated nozzle that focuses low in
all three dimensions ( Figure 5.2 ).
he SU-8 nozzle of Figure 5.2 is an example of miniaturization of a macroscale component.
However, can a focused low be achieved in a simpler way, one perhaps that does not require
exotic photolithography equipment, that is compatible with PDMS molding, or that exploits