Youngki Choe

Microparticle trapping in an ultrasonic Bessel beam

This paper describes an acoustic trap consisting of a multi-foci Fresnel lens on 127 μm thick lead zirconate titanate sheet. The multi-foci Fresnel lens was designed to have similar working mechanism to an Axicon lens and generates an acoustic Bessel beam, and has negative axial radiation force capable of trapping one or more microparticle(s). The fabricated acoustic tweezers trapped lipid particles ranging in diameter from 50 to 200 μm and microspheres ranging in diameter from 70 to 90 μm at a distance of 2 to 5 mm from the tweezers without any contact between the transducer and microparticles.

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.

On-chip integration of eight directional droplet ejectors for inking a spot with eight droplets without ejector movement

This paper describes an on-chip acoustic ejector array consisting of eight directional droplet ejectors that was designed to ink a spot with eight different droplets without having to move the ejectors. Each of the eight directional ejectors consistently ejects uniform droplets in diameter of 51 µm with a directional angle about 17° (with respect to the normal direction of the liquid surface). When a glass substrate was placed 8 mm away from the ejector array chip, all the ejected droplets from the 8 ejectors were placed within 399 × 1080 µm2 area. If we exclude two ejectors which had bad alignment with the others, all the 6 droplets were placed within 238 × 380 µm2 area.

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.

Peptide Synthesis on Glass Substrate Using Acoustic Droplet Ejector

This paper describes the synthesis of a 9-mers-long peptide ladder structure of glycine on a modified glass surface using a nanoliter droplet ejector. To synthesize peptide on a glass substrate, SPOT peptide synthesis protocol was followed with a nozzleless acoustic droplet ejector being used to eject about 300 droplets of preactivated amino acid solution to dispense 60 nL of the solution per mer. The coupling efficiency of each mer was measured with FITC fluorescent tag to be 96%, resulting in net 70% efficiency for the whole 9-mer-long peptide of glycine. Usage of a nanoliter droplet ejector for SPOT peptide synthesis increases the density of protein array on a chip.This paper describes the synthesis of a 9-mers-long peptide ladder structure of glycine on a modified glass surface using a nanoliter droplet ejector. To synthesize peptide on a glass substrate, SPOT peptide synthesis protocol was followed with a nozzleless acoustic droplet ejector being used to eject about 300 droplets of preactivated amino acid solution to dispense 60 nL of the solution per mer. The coupling efficiency of each mer was measured with FITC fluorescent tag to be 96%, resulting in net 70% efficiency for the whole 9-mer-long peptide of glycine. Usage of a nanoliter droplet ejector for SPOT peptide synthesis increases the density of protein array on a chip.

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.

MEMS ultrasonic transducers for highly sensitive Doppler velocity sensor for low velocity measurement

This paper describes a novel, highly-sensitive ultrasonic Doppler velocity sensing system for low velocity measurement in portable navigation systems. It is a compact velocity sensing system, in which MEMS ultrasonic transducers are incorporated with phase-locked-loop (PLL) circuitry for frequency detection and signal processing. The achieved voltage-velocity sensitivity is 0.22 V/(mm/s) and the minimum detectable velocity is 0.67 mm/s, corresponding to 0.11 Hz in Doppler frequency. To the best of our knowledge, the minimum detectable velocity is the best reported in literature. Also, the output of the PLL is a DC voltage linearly related to the velocity, and there is no need to convert the frequency shift to analog voltage.

Electrical control of droplet direction with phase-varied fresnel lens on acoustic wave liquid ejector

This paper describes a novel design of a multi-directional acoustic ejector with capability of electrical control on the droplet ejection angle by changing the operating frequency. The newly developed ejector consistently ejects uniform droplets in diameter of 70 µm, with electrical control of the directional angle from −30° to 35° (with respect to normal direction of liquid surface plane) as the operating frequency is varied from 16.78 MHz to 19.08 MHz. To produce the electrically adjustable oblique ejections of nano-liter droplets, destructive wave interference is intentionally introduced through a phase-varied lens. With the novel lens, the direction of the droplet ejection depends monotonically on the operating frequency of the driving signal. This paper presents the experimental results, as well as the theoretical analysis and simulation verification of the phase-varied lens design that gives the electrical control on the direction of ejected droplets.

Ultrasonic microparticle trapping by multi-foci Fresnel lens

This paper describes an acoustic tweezers consisting of a multi-foci Fresnel lens on 127 µm thick PZT sheet, designed to capture micron-sized particles. The multi-foci Fresnel lens was designed to have similar working mechanism as that of an axicon lens to generate an acoustic Bessel beam and, correspondingly, to generate negative axial radiation force capable of trapping one or more microparticle(s). The fabricated acoustic tweezers successfully trapped lipid particles ranging in diameter from 50 to 200 µm and microspheres ranging in diameter from 70 to 90 µm at a distance of 2 to 5 mm from the tweezers without any contact between the transducer and microparticles.