Biomedical Engineering Reference
In-Depth Information
of complex diseases like cancer because disease heterogeneity
makes single marker tests inadequate. Moreover, detection of
markers associated with different stages of disease pathogenesis
could facilitate early detection.
The examples described in this Section illustrate the unique
capabilities of nanowire-based field-effect sensor device arrays for
medicine and life sciences, broadly defined. Throughout these ex-
periments, devices have shown very good device-to-device abso-
lute detection reproducibility and simultaneous false positive sig-
nals were discriminated; complementary electrical signals from p-
and n-type devices provide a simple yet robust means for detecting
false positive signals from either electrical noise or nonspecific
binding of protein. It is important to note that these exquisite sensi-
tivities were also verified by Reed's group in 2007 that used top-
down fabricated NWs to demonstrate specific label free detection
of proteins below 100 fM concentration, as well as real-time moni-
toring of the cellular immune response.
However, some limitations also exist. An intrinsic limitation
of FET devices is that the detection sensitivity depends on solution
ionic strength 25a . In the case of nanowire FET-sensing, low salt
(<1 mM) buffers are required to prevent screening of the charge-
based electronic signal. Because blood serum samples have high
ionic strength, diagnostic will require means to overcome the de-
ceptive shielding. A simple desalting step before analysis was
demonstrated to allow for highly sensitive assays. 15b Recently, to
overcome these limitations, Reed's group 25b has developed an in-
line microfabricated device that operates upstream of the nanosen-
sors to purify biomarkers of interest prior to the detection step. The
microfluidic purification chip captures the protein biomarkers di-
rectly from physiological solutions and, after a washing step is
performed, the antigens are released into a clean low ionic strength
buffer suitable for high-sensitivity sensing, as schematically de-
scribed in Fig. 3B . First, a blood sample flows through the chip
and the chip-bound antibodies bind to the soluble biomarkers, es-
sentially purifying these molecules from whole blood. After this
capture step, wash and sensing buffers are perfused through the
device. Flow is then halted, and the sensing buffer-filled chip is
irradiated with ultraviolet (UV) light, resulting in cleavage of the
photolabile group and release of the bound biomarker-antibody
complexes. Finally, the released purified antigen molecules, bound
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