Biomedical Engineering Reference
In-Depth Information
[ 32 ] and have been utilized in development of bead-based microfluidic ELISA
systems [ 33 ]. However, these micromechanical valves require high pressure often
supplied by gas tanks. Active microvalves which are based on elastomeric deflec-
tions and are better suited at point-of-care settings include hydraulic (liquid)
deflection based on magnetic actuation with solenoids [ 34 ] and torque-actuated
deflection using small machine screws [ 35 ].
Passive approaches, which leverage differences in fluid behavior from varying
microchannel geometries in capillary systems, are attractive because they do not
require external power and moving off-chip parts. Such control mechanisms include
delay valves, which merge smaller channels into larger channels to allow for smooth
collection of incoming fluid streams at different flowrates; stop valves, which reduce
the width of a microfluidic path using a restriction and enlarge it abruptly to
reduce capillary pressure of a liquid front to zero; and trigger valves, which are the
assembly of multiple stop valves preventing further fluid flow into a common outlet
until the arrival of all inlet streams [ 36 ]. Some of these microfluidic control elements
have been integrated on a chip for detection of C-reactive protein [ 37 ]. In addition,
check valves have been implemented on a microfluidic device for multistep ELISA,
detecting botulinum neurotoxin [ 38 ].
We have developed valveless delivery of reagents in microfluidic systems which
have been demonstrated for detecting anti-HIV antibodies [ 39 ] and anti-treponemal
antibodies [ 30 ]. The plug-based reagent delivery is a robust and low-cost approach
for delivering multiple reagents without the need for on-chip valves.
Fluid Actuation and Delivery
Movement of fluids by capillary forces is reliable and does not require external
power or moving parts. Miniaturized immunoassays based on capillary forces have
been used for detecting cardiac markers [ 40 ] and luteinizing hormone [ 41 ]. Paper-
based microfluidic systems also leverage capillary flow and have been used to
detect anti-HIV antibodies [ 42 ]. Despite the need for external power, electrophoretic
immunoassays in capillaries can be utilized if the power requirement is low
(allowing for battery operation) and external instrumentation integrated in a single,
easy-to-use device; such has been demonstrated in a promising proof-of-concept
device for integrated, rapid, point-of-care testing of biotoxins ricin, Shiga toxin I,
and Staphylococcal enterotoxin B [ 28 ], as well as in a rapid bioassay for endogenous
matrix metalloproteinase-8 in saliva [ 43 ]. Pneumatic-based actuation of fluids can
be suited for point-of-care settings, for example, in the manual operation of on-card
bellows in the commercially available ABO blood typing chip by Micronics. A hand
pump can also be used for pneumatic fluid actuation in microfluidic immunoassays
[ 30 , 39 ]. Injection-molded centrifugal-based platforms (CDs) rely on spin frequency
to drive fluid movement, and movements are gated by capillary or hydrophobic
valves; these can be suited for point-of-care testing in resource-limited settings,
where in one example a centrifugal bead-based immunoassay was developed for
the detection of antigen and antibody to hepatitis B virus [ 44 ].
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