Anderson Lin

Ultrahigh Frequency Lensless Ultrasonic Transducers for Acoustic Tweezers Application

Similar to optical tweezers, a tightly focused ultrasound microbeam is needed to manipulate microparticles in acoustic tweezers. The development of highly sensitive ultrahigh frequency ultrasonic transducers is crucial for trapping particles or cells with a size of a few microns. As an extra lens would cause excessive attenuation at ultrahigh frequencies, two types of 200‐MHz lensless transducer design were developed as an ultrasound microbeam device for acoustic tweezers application. Lithium niobate single crystal press‐focused (PF) transducer and zinc oxide self‐focused transducer were designed, fabricated and characterized. Tightly focused acoustic beams produced by these transducers were shown to be capable of manipulating single microspheres as small as 5 µm two‐dimensionally within a range of hundreds of micrometers in distilled water. The size of the trapped microspheres is the smallest ever reported in the literature of acoustic PF devices. These results suggest that these lensless ultrahigh frequency ultrasonic transducers are capable of manipulating particles at the cellular level and that acoustic tweezers may be a useful tool to manipulate a single cell or molecule for a wide range of biomedical applications. Biotechnol. Bioeng. 2013; 110: 881–886.

Microelectromagnetic energy harvester with integrated magnets

This paper presents a microelectromagnetic power generator with integrated magnets that can be fabricated on silicon wafers in a batch process. The generator is fabricated by MEMS technologies and characterized at different vibration frequencies, amplitudes and load resistances. This compact generator occupies a volume of 15×13×0.4mm3, as no external permanent magnets are needed. Experimental results show that with a 20-turn spiral coil, the device can generate an induced electromotive force (EMF) of 0.27mV at a vibration frequency and amplitude of 350Hz and 10µm, respectively.

Explosive trace detection with FBAR-based sensor

This paper describes explosive trace detection through mass sensing with film bulk acoustic resonator (FBAR) coated with antibodies. Mass sensing for a specific explosive is done with the use of antibody made specifically for the targeted explosive. Antibodies were immobilized on the backside of FBAR mass sensors using an antibody immobilization protocol. When the specific explosive is exposed to the sensor, it binds to the antibody on the sensor, causing a shift in the resonant frequency of the FBAR sensor. This sensing technique has been shown to selectively detect vapor traces of TNT (trinitrotoluene, a common explosive) and RDX (cyclotrimethylenetrinitramine which has one of the lowest vapor pressures among various explosives) without any pre-concentrator.

Edge-released, piezoelectric MEMS acoustic transducers in array configuration

A sensitive, broad-bandwidth piezoelectric microelectromechanical systems (MEMS) transducer based on frequency interleaving of resonant transducers was designed and fabricated. A sputter-deposited piezoelectric zinc oxide (ZnO) thin film on the diaphragm is used to sense and generate acoustic pressure. A high compliance cantilever and spiral-beam-supported diaphragms are designed and built on the edge-released MEMS structure to release initial residual stress and to avoid in-plane tension when bent. Stress compensation has been achieved by adjusting the thickness of each layer of the cantilever and by compensating for the ZnO films compressive stress with the bimorph structure of the spiral-beam. For a given pressure level and diaphragm size, the maximum strain on the spiral-beam-supported diaphragm is about an order of magnitude larger than that of a rectangular cantilever diaphragm. Also, the acoustic transducer built on the spiral-beam-supported diaphragm has a much higher sensitivity (but with less tolerance on the fabrication process variation and at the cost of lower usable bandwidth) than the one built on a rectangular cantilever diaphragm. By connecting many transducers in parallel, both the sensitivity and acoustic output were improved about 30 times. The interleaving of the transducers increased not only the sensitivity, but also broadened the useable bandwidth.

A Self-Focusing Acoustic Transducer That Exploits Cytoskeletal Differences for Selective Cytolysis of Cancer Cells

Biophysical effects of ultrasonic energy in tissue include changes induced by heat, cavitation, and body force (radiation energy). Conventional acoustic devices generate low-frequency (1-4 MHz) high-intensity acoustic waves (> 103 W/cm2), which cause tissue destruction primarily through thermal or cavitation effects. However, these effects may be difficult to precisely control and not specific for cancerous cells over normal tissue. Here, we describe the design, fabrication, and therapeutic potential of high-frequency (18-MHz) acoustic irradiation with a self-focusing acoustic transducer (SFAT). A surface micromachining technique was used on a piezoelectric substrate to produce a SFAT device capable of focusing acoustic energy within an area of 100 μm in diameter at the 800-μm focal length. As we sought to minimize potentially nonspecific heat or cavitation effects by acoustic irradiation, operational parameters were chosen to study bioeffects of the device in the absence of tissue heating or biological effects due to cavitation. By varying the acoustic energy, we identified an acoustic intensity threshold (AIT) of 0.15 W/cm2 at 17.3 MHz, sufficient to cause this cytolysis effect in human prostate cancer cells 22RV1 without heat or cavitation. Next, we compared the AIT in various cell lines representative of benign and malignant prostate, breast, and skin cells and observed lower AITs in cancer cells over nonmalignant variants. As decreased stiffness (increased compliance) is a biomechanical characteristic, which differs between malignant and nonmalignant cell lines, we hypothesized that a less organized actin cytoskeletal pattern, which is known to be associated with decreased cell stiffness, would correlate with changes in the AIT. Actin staining of cytoskeletal structures confirmed an association between a pattern of diffuse and less organized actin filaments with decreased AIT. Moreover, the same trend of decreased actin organization and decreased AIT was observed following treatments that changed actin patterns in the MCF-10A breast epithelial cell line. These results suggest that biomechanical properties make malignant cells specifically sensitive to cytolysis caused by this form of acoustic energy. In summary, we describe a miniaturized acoustic transducer capable of producing a heatless and cavitation-free, cancer-specific focused cytolysis by direct body force (radiation pressure) effects alone. Ultimately, this device may lead to a miniaturized cancer-treatment system that can be used to focally and specifically ablate cancerous tissue with microscopic precision.

Real-time label-free detection of DNA synthesis by FBAR-based mass sensing

This paper reports a real-time detection of DNA polymerase reaction through mass sensing with film bulk acoustic resonator (FBAR) coated with self-assembled DNA sequences. This label-free, real-time detection of DNA synthesis can potentially lead to detection of single nucleotide addition for DNA sequencing application, which can be developed into a low-cost, third-generation DNA sequencing system capable of reading thousands of nucleotides in a single run.

Selectivity and Long-Term Reliability of Resonant Explosive-Vapor-Trace Detection based on Antigen-Antibody Binding

This paper reports experimental results on the selectivity and long-term reliability of the explosive-vapor-trace detection based on antigen-antibody binding on a film bulk acoustic resonator (FBAR). An FBAR coated with specific antibody was shown to be able to detect vapor trace of TNT (Trinitrotoluene) or RDX (Cyclotrimethylenetrinitramine) without any pre-concentrator [1], but its false alarm rate and long-term reliability have never been experimentally investigated. This paper confirms that the anti-TNT coated FBAR sensor indeed responds to TNT vapor very selectively with permanent resonant frequency shift, as expected since an antigen binds only to its specific antibody. Also experimentally obtained is a surprisingly long lifetime (up to a month) of the anti-TNT at room temperature.

Micro-localized cell lysis by low power Focused Acoustic Transducer

In this study, we designed and fabricated Self Focused Acoustic Transducer (SFAT) for micron-sized localized cytolysis. Monolayer 22RV1 prostate cancer cells were cultured in the cell culture chamber and locally lysed by the SFAT. Various electric powers and operating frequencies of actuating pulsed signal were applied to characterize the localized cell lysis effects. The cell lysis area was around 2.28×10-9 m2 and 1.64×10-9 m2, when the acoustic waves produced by the transducer were 17.3 and 52 MHz, respectively. The minimum electric power required for the cell lysis of 22RV1 is as low as 9 mW, which produces an acoustic intensity 0.15 W/cm2 at the focal spot. The amount of mRNA released in the culture media was increased more than 10 times after the cytolysis. According to experiment results, the size of lysed cells area is determined by the acoustic-wave frequency, and very little by the electric power applied to the device above a threshold. Signs of inertia cavitation phenomena such as bubble generation or temperature raise were not observed. Therefore, low-power micron-sized cell lysis without cavitation may have practical applications relating to cancer diagnosis and therapeutics.

Combinatory localized cytolysis with micron precision by acoustic transducer array for fast screening of drug induced cytoskeleton alteration

This paper reports combinatory localized-cytolysis by an array of MEMS ultrasonic transducers for fast screening of drug-induced cytoskeleton variation with fluorescence-stained cytolysis assay. An array of 6×6 Self Focused Acoustic transducers (SFATs) and disposable cell culture microwells were fabricated for the cytolysis and the fluorescence stain analysis. Cells were cultured in the microwells, and different drugs were applied to the cells to modify cell cytoskeletons. Multi-spot, localized cytolysis with micron precision was carried out with the SFAT array. Experimental results show that the SFAT array produced localized cytolysis with a focal spot of about 100-300 microns in diameter in multiple microwells, and the changes of the acoustic intensity threshold (AIT) for cytolysis were in accord with the alterations of the cytoskeleton induced by the drug treatments. Therefore, cytoskeleton-specific fast drug screening can be realized by observing the variation of the AIT. Since the SFAT array can lyse multiple cell samples within 3 minutes, it is easy to discern the lysed cells under fluorescent microscope, and the SFAT array system improves the efficiency and simplicity of the drug screening greatly.

Frequency-multiplexed combinatory mass sensing with single data line from multiple integrated film bulk acoustic resonators

This paper presents a novel array of four film bulk acoustic resonators (FBAR) having four distinct fundamental resonant frequencies that offers parallel and/or combinatory mass sensing of multiple chembio species, such as various proteins. To achieve the multiple resonant frequencies, we connect multiple FBARs (having slightly different resonant frequencies, thus each representing a unique sensor) in parallel, and form one FBAR (out of the multiple) on a chip. This way, when we measure the frequency shifts of the arrayed FBAR through a network analyzer, we have multiple resonant frequencies, each of which will change as a function of added mass (of chembio species), independent of the others.