Biomedical Engineering Reference
In-Depth Information
be easily arrayed in large two-dimensional arrays. he group reported an increase in the per-
meability of skin on microneedle penetration by three to four orders of magnitude; however,
it was observed that occasionally the tip of a few microneedles would break, which raised a
biocompatibility concern.
Prausnitz' irst silicon microneedles were essentially simple solid sharp tips that were so
small (and short) that did not cause pain (they never reached the nerve layers) but were also
limited in what they could be loaded with: they could only deliver drugs in dry form. One
year later, the same group reported the irst hollow microneedles (made in metal and featuring
an aperture), which allowed for delivering arbitrary solutions through the back of the wafer
without complicated interfaces.
Figure 8.13c
shows an example of out-of-plane, 200-μm-tall
hollow microneedles fabricated in silicon by Dorian Liepmann's group from the University of
California at Berkeley. he 40-μm-diameter hole at the center of the tips is a through hole, so
the tips can be fed from the opposite side of the wafer from a regular syringe (see inset in
Figure
8.13c
) to inject compounds past the stratum corneum, the 10- to 15-μm-thick outer layer of the
skin. However, these hollow microneedles tended to get clogged during insertion by the tissue,
which changed the luidic resistance of the array (because they were all connected to the same
inlet). In 2003, Göran Stemme's group from the Royal Institute of Technology in Stockholm,
Sweden (in June), and van der Berg's group from the University of Twente in the Netherlands (in
December) independently reported diferent ways of producing out-of-plane silicon micronee-
dles with side openings (which prevented the clogging problem). What else could one ask for?
here was still the risk of breakage because silicon's biocompatibility was not optimal. Hence,
Seung Lee's group from KAIST in Daejeon (Korea) fabricated polymeric tips in PMMA (a very
biocompatible polymer, used in many implants and contact lenses) using inclined deep X-ray
3 Coating cycles
9 Coating
cycles
b
a
200 µm
Guinea pig cadaver skin section after 10-min microneedle insertion
H&E staining
Fluorescence
c
d
BCG vaccine
(6 coating cycles)
200 µm
FIGURE 8.14
Microneedles. for. tuberculosis. vaccination.. (From. Yasuhiro. Hiraishi,. Subhadra.
Nandakumar,.Seong-O.Choi,.Jeong.Woo.Lee,.Yeu-Chun.Kim,.James.E..Posey,.Suraj.B..Sable,.and.
Mark.R..Prausnitz,.“Bacillus.Calmette-Guérin.vaccination.using.a.microneedle.patch,”.
Vaccine
,.29,.
2626,.2011..Reprinted.with.permission.of.Elsevier.)
