Lingtao Wang

Mass spectrometric sampling of a liquid surface by nanoliter droplet generation from bursting bubbles and focused acoustic pulses: application to studies of interfacial chemistry.

The complex chemistry occurring at the interface between liquid and vapor phases contributes significantly to the dynamics and evolution of numerous chemical systems of interest, ranging from damage to the human lung surfactant layer to the aging of atmospheric aerosols. This work presents two methodologies to eject droplets from a liquid water surface and analyze them via mass spectrometry. In bursting bubble ionization (BBI), droplet ejection is achieved via the formation of a jet following bubble rupture at the surface of a liquid to yield 250 μm diameter droplets (10 nL volume). In interfacial sampling by an acoustic transducer (ISAT), droplets are produced by focusing pulsed piezoelectric transducer-generated acoustic waves at the surface of a liquid, resulting in the ejection of droplets of 100 μm in diameter (500 pL volume). In both experimental methodologies, ejected droplets are aspirated into the inlet of the mass spectrometer, resulting in the facile formation of gas-phase ions. We demonstrate the ability of this technique to readily generate spectra of surface-active analytes, and we compare the spectra to those obtained by electrospray ionization. Charge measurements indicate that the ejected droplets are near-neutral (<0.1% of the Rayleigh limit), suggesting that gas-phase ion generation occurs in the heated transfer capillary of the instrument in a mechanism similar to thermospray or sonic spray ionization. Finally, we present the oxidation of oleic acid by ozone as an initial demonstration of the ability of ISAT-MS to monitor heterogeneous chemistry occurring at a planar water/air interface.

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.

1E-1 Photoacoustic Microscopy with a 30MHz Array and Receive System

Photoacoustic microscopy is a hybrid imaging modality which captures the contrast advantage of optical imaging with the resolution advantage of ultrasonic imaging. This technique provides great promise for studying the structure and dynamics of tissue microvasculature in development and pathogenesis. In this paper we present results of a new high frequency array based photoacoustic microscopy system (PAM) using an Nd:YAG pumped tunable dye laser, a 30 MHz piezo composite linear array and a custom multi-channel receiver system. Using offline delay and sum beamforming and beamsteering, phantom images were obtained from a 6 mum carbon fiber in water at a depth of 8 mm. The measured axial and lateral spatial resolution of the system was 100 plusmn 5 mum and 45 plusmn 5 mum, respectively. In situ photoacoustic images were obtained of vessels less than 100 mum in diameter at depths of 3 mm below the skin surface in a Sprague Dawley rat

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.

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.

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.