Biomedical Engineering Reference
In-Depth Information
based on the details of the motion of the ions as they transit through the ields. In most mass
spectrometers, the sample molecules are converted into ions from gas phase by means of an ion
source. he use of electrospray ionization allows for using liquid samples.
he irst reports of microluidic devices that implemented electrospray ionization-mass spec-
trometry used electrospray from channels terminating at the edge of the device, such as the
glass device reported in 1997 by Barry Karger's group at Northeastern University. Other groups
have used conventional electrospray emitters (e.g., fused-silica capillaries) attached to the
device. However, these approaches are nonoptimal because the spray at the edge of the device
is troubled by droplet formation. Importantly, electrospray nozzles can be miniaturized using
micromachining techniques so that the nozzles can be integrated with the device (
Figure 4.29
),
producing reliable sprays. he irst integrated micromachined emitter, made of silicon nitride,
was reported by Terry Lee's group from the Beckman Research Institute of the City of Hope
(Duarte, CA) at the
Transducers '97
conference but the design was quickly abandoned because
of unreliable performance. he irst micromolded (PDMS) emitter tip integrated as part of a
microluidic device was demonstrated by Daniel Knapp's team from the Medical University of
South Carolina in 2001. he performance of the nozzle is logically a function of its shape and
materials, and thus, many groups have devoted great eforts not only to develop better electro-
spray emitters but also to understand the fundamentals of electrospray emission.
he diameter of the nozzle and the low rate at which luid is ejected are the critical param-
eters for measuring the performance of a microfabricated electrospray mass spectrometer.
Present-day nozzles with inner dimensions on the range of a few microns are capable of gener-
ating a “nanospray,” resulting in higher ionization eiciency (because the droplets are smaller,
the number of charges available per analyte molecule is much higher in a nanospray, which
enhances the probability of ionization), lower electrospray voltages (which allows the nozzle to
be positioned closer to the mass spectrometer), and less sample consumption compared with
traditional electrosprays.
In 2007, a team led by Jonathan Sweedler and Ralph Nuzzo from the University of Illinois at
Urbana-Champaign was able to capture the release of neuropeptide by single
Aplysia californica
bag cell neurons using mass spectrometry imaging. Peptide release was not analyzed online—
the peptides were chemically captured by the surface (a self-assembled monolayer of octadecyl
alkyl chains, which happen to adsorb the neuropeptides) and the surface was interrogated by
scanning it, performing a mass spectrometric analysis at each “pixel” of the sample. Imaging
resolution ranged from 100 to 200 μm.
4.8 Biochemical Analysis Using Force Sensors
Another very successful strategy for detecting binding or ainities between biomolecules is
based on measuring the force of adhesion between them. here are many devices that can be
used to measure forces, and many do not use microfabricated components (e.g., laser tweezers),
but the simplest is probably the spring, or its cousin, the spring board (also known as cantilever)
because it translates force to displacement.
Cantilevers have been used to detect forces for centuries: the force applied at the tip produces
a displacement, which can be measured; the relationship between the force,
F
, and the tip dis-
placement,
d
(usually linear,
F
=
kd
) can be calibrated with known applied forces or weights, so
that when an unknown force is applied, the value can be known by interpolation. Without going
into the details of how the formula is derived, for small delections, the relationship between
d
and
F
for a cantilever of width,
w
, thickness,
t
, and length,
L
, can be expressed as:
E
wt
L
3
1
4
(
4.1
)
F
=
d
3
