Surface acoustic waves (SAWs), are electro-mechanical waves that form on the surface of piezoelectric crystals. Because they are easy to construct and operate, SAW devices have proven to be versatile and powerful platforms for either direct chemical sensing or for upstream microfluidic processing and sample preparation. This review summarizes recent advances in the development of SAW devices for chemical sensing and analysis. The use of SAW techniques for chemical detection in both gaseous and liquid media is discussed, as well as recent fabrication advances that are pointing the way for the next generation of SAW sensors. Similarly, applications and progress in using SAW devices as microfluidic platforms are covered, ranging from atomization and mixing to new approaches to lysing and cell adhesion studies. Finally, potential new directions and perspectives on the field as it moves forward are offered, with a specific focus on potential strategies for making SAW technologies for bioanalytical applications.
Extracellular vesicles (EV) containing microRNAs (miRNAs) have tremendous potential as biomarkers for the early detection of disease. Here, we present a simple and rapid PCR-free integrated microfluidics platform capable of absolute quantification (<10% uncertainty) of both free-floating miRNAs and EV-miRNAs in plasma with 1 pM detection sensitivity. The assay time is only 30 minutes as opposed to 13 h and requires only ~20 μL of sample as oppose to 1 mL for conventional RT-qPCR techniques. The platform integrates a surface acoustic wave (SAW) EV lysing microfluidic chip with a concentration and sensing microfluidic chip incorporating an electrokinetic membrane sensor that is based on non-equilibrium ionic currents. Unlike conventional RT-qPCR methods, this technology does not require EV extraction, RNA purification, reverse transcription, or amplification. This platform can be easily extended for other RNA and DNA targets of interest, thus providing a viable screening tool for early disease diagnosis, prognosis, and monitoring of therapeutic response.
Exosomes carry microRNA biomarkers, occur in higher abundance in cancerous patients than in healthy ones, and because they are present in most biofluids, including blood and urine, these can be obtained noninvasively. Standard laboratory techniques to isolate exosomes are expensive, time consuming, provide poor purity, and recover on the order of 25% of the available exosomes. We present a new microfluidic technique to simultaneously isolate exosomes and preconcentrate them by electrophoresis using a high transverse local electric field generated by ion-depleting ion-selective membrane. We use pressure-driven flow to deliver an exosome sample to a microfluidic chip such that the transverse electric field forces them out of the cross flow and into an agarose gel which filters out unwanted cellular debris while the ion-selective membrane concentrates the exosomes through an enrichment effect. We efficiently isolated exosomes from 1× PBS buffer, cell culture media, and blood serum. Using flow rates from 150 to 200 μL/h and field strengths of 100 V/cm, we consistently captured between 60 and 80% of exosomes from buffer, cell culture media, and blood serum as confirmed by both fluorescence spectroscopy and nanoparticle tracking analysis. Our microfluidic chip maintained this recovery rate for more than 20 min with a concentration factor of 15 for 10 min of isolation.
The presence of a small number (∼1000)
of charged nanoparticles
or macromolecules on the surface of an oppositely charged perm-selective
membrane is shown to sensitively gate the ionic current through the
membrane at a particular voltage, thus producing a voltage signal
much larger than thermal noise. We show that, at sufficiently high
voltages, surface vortices appear on the membrane surface and sustain
an ion-depleted boundary layer that controls the diffusion length
and ion current. An asymmetric vortex bifurcation occurs beyond a
critical voltage to reduce the diffusion length and the differential
resistance by half. Surface nanoparticles and molecules only affect
this transition voltage in the membrane I–V curve. It is shown to shift by 2 ln10 (RT/F) ∼ 0.12 V for every decade increase in
bulk target concentration, independent of sensor dimension and target/probe
pair. Such universal features of the surface charge-sensitive nonlinear
and nonequilibrium conductance allow us to develop very robust (a
2–3 decade dynamic range for highly heterogeneous samples with
built-in control) yet sensitive (subpicomolar) and selective biosensors
for highly charged molecules like nucleic acids and endotoxinsand
for proteins with charged nanoparticle reporters.
In this work, a guided shear horizontal mode surface acoustic wave (SH-SAW) sensor, fabricated by patterning gold (Au) interdigitated electrodes (IDE) on a 64°YX-LiNbO 3 based piezoelectric substrate, was used for the detection of heavy metal compounds. A flow cell, with a reservoir volume of 3 µl, which employs inlet and outlet valves for the microfluidic chamber and polydimethylsiloxane (PDMS) based microfluidic channels, was also designed and fabricated using an acrylic material. The frequency based response of the SAW sensor towards varying concentrations of heavy metal compounds such as lead nitrate (PbNO 3) and cadmium nitrate (CdNO 3) were investigated. As the surface acoustic wave propagates on the substrate, between input and output IDEs, a shift in the resonant frequency of the SAW device was observed due to the change in velocity of the wave caused by the varying concentrations of the test analytes. The results obtained demonstrated the capability of the system to detect picomolar level concentrations. The response of the SAW sensor is analyzed and presented in this paper.
In this study, a shear horizontal mode surface acoustic wave (SH-SAW) sensor, was designed and fabricated for the detection of heavy metals. The SH-SAW sensor was photolithographically fabricated by patterning gold (Au) interdigitated electrodes (IDE) and reflectors on the surface of a 64° YX-LiNbO 3 based piezoelectric substrate. A flow cell, with a reservoir volume of 3 µl, which employs inlet and outlet ports for the microfluidic chamber and polydimethylsiloxane (PDMS) based microfluidic channels, was also designed and fabricated using acrylic material. Phenol and naphtho[2,3-a]dipyrido[3,2-h:2'3'-f] phenazine-5,18-dione (QDPPZ) were employed as the sensing layers for mercury and nickel ions, respectively. The frequency based response of the SH-SAW sensor demonstrated picomolar level detection for mercury nitrate (Hg(NO 3 ) 2 ) and nickel nitrate (Ni(NO 3 ) 2 ).
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