Biomedical Engineering Reference
In-Depth Information
Because DNA microarrays are not really microfabricated, they will not be discussed fur-
ther here. However, there have been a few notable attempts to miniaturize this technology.
he challenge is essentially to deposit small volumes of large numbers of DNA solutions (each
originally separated in a macroscopic vial) in a microarray format. Several solutions have been
proposed in addition to those by Stephen Fodor and Pat Brown, but among those, two deserve
a special creativity mention: the ingenious bead arrays invented by David Walt (now marketed
by Illumina) and the quasimagical electroaddressable DNA deposition conceived by Susan
Brozik.
4.6.1.4 Self-Assembled Microarrays of Beads
In 1998, David Walt, a chemistry professor at Tuts University (Cambridge, Massachusetts),
pondering about the high cost of Afymetrix's chips, had a revolutionary idea: Why did the
DNA-sensing spots need to be printed? It occurred to him that they could be prefabricated
in solution as
beads
(!) and then deposited into approximately 3-μm-deep, 3.6-μm-diameter
microwells that itted just one approximately 3.1-μm-diameter bead each (
Figure 4.16
). At this
scale, the viscosity of water makes it virtually impossible for a bead to be dislodged from a
microwell once it is inside. Beads can be easily derivatized with DNA (or any other biomolecule)
as well as with dyes (to distinguish them from one another)—by the millions. Of course, every
time that a mixture of beads is deposited on an array, the arrangement of beads changes (unlike
with Afymetrix' arrays), but as long as the beads are encoded with a dye, their identity can be
decoded. he microwell array can potentially be built in many ways, but Walt's group (in the
same article!) came up with a cunningly clever design: take a bundle of glass iber optics and
dip the end of it in hydroluoric acid (HF) for a few minutes (the core of the ibers is pure quartz,
and thus etches faster in HF than the cladding, which is doped glass)—this results in a set of
glass wells, as shown in the top image of
Figure 4.16
; the reason this design is so clever is that
it is cheap to fabricate (does not require access to a clean room for photolithography) and, most
importantly, it is already
optically wired
: each iber optic can be used to project as well as collect
light onto the beads, and it is straightforward to interface the other end of the bundle with a
digital camera for data acquisition.
5 µm
FIGURE 4.16
Optically.addressable,.self-assembled.microarrays.of.beads..(From.Karri.L..Michael,.
Laura.C..Taylor,.Sandra.L..Schultz,.and.David.R..Walt,.“Randomly.ordered.addressable.high-density.
optical.sensor.arrays,”.
Anal. Chem.
.70,.1242-1248,.1998..Figure.contributed.by.David.Walt.)
