MEMS piezoelectric resonant microphone array for lung sound classification.

This paper reports a highly sensitive piezoelectric microelectromechanical systems (MEMS) resonant microphone array (RMA) for detection and classification of wheezing in lung sounds. The RMA is composed of eight width-stepped cantilever resonant microphones with Mel-distributed resonance frequencies from 230 to 630 Hz, the main frequency range of wheezing. At the resonance frequencies, the unamplified sensitivities of the microphones in the RMA are between 86 and 265 mV Pa-1, while the signal-to-noise ratios (SNRs) for 1 Pa sound pressure are between 86.6 and 98.0 dBA. Over 200-650 Hz, the unamplified sensitivities are between 35 and 265 mV Pa-1, while the SNRs are between 79 and 98 dBA. Wheezing feature in lung sounds recorded by the RMA is more distinguishable than that recorded by a reference microphone with traditional flat sensitivity, and thus, the automatic classification accuracy of wheezing is higher with the lung sounds recorded by the RMA than with those by the reference microphone, when tested with deep learning algorithms on computer or with simple machine learning algorithms on low-power wireless chip set for wearable applications.

Ring-Focusing Fresnel Acoustic Lens for Long Depth-of-Focus Focused Ultrasound with Multiple Trapping Zones.

This paper describes a novel acoustic transducer with dual functionality based on 1-mm-thick lead zirconate titanate (PZT) substrate with a modified air-cavity Fresnel acoustic lens on top. Designed to let ultrasound waves focus over an annular ring region, the lens generates a long depth-of-focus Bessel-like focal beam and multiple trapping zones based on quasi-Airy beams and bottle beams. With 2.32 MHz sinusoidal driving signal at 150 Vpp, the transducer produces a focal zone with 9.9 mm depth-of-focus and 0.8 MPa peak pressure at a focal length of 31.33 mm. With 2.32 MHz continuous sinusoidal drive at 30-35 Vpp, the transducer is able to trap multiple polyethylene microspheres (350-1,000 µm in diameter and 1.025-1.130 g/cm3 in density) in water either simultaneously (when suspended by mechanical agitation or released from water surface) or sequentially (when placed one after another with a pipette). The largest particles the transducer could trap are two 1-mm-diameter microspheres stuck together (1.07 mg in weight, lifted by buoyance and 0.257 µN acoustic-field-induced force). When the transducer is moved laterally, some firmly trapped microspheres follow along the transducer's movement, while being trapped. When trapped, some microspheres can rotate due to the rotation torque generated by the quasi-Airy beams.

Contactless Single Cell Extraction from Monolayer Cell Culture Using A MEMS Acoustic Droplet Ejector.

OBJECTIVE: To achieve a contactless and damage-less extraction of a single (or a few) human retinal pigment epithelial (RPE) cell(s) from a cell monolayer with acoustic droplet ejection. METHODS: An acoustic droplet ejector based on a self-focusing acoustic transducer (SFAT) is designed, microfabricated, and placed on a precision movable stage that aligns it to the targeted cell(s) in a Petri dish. The device delivers 20.1 MHz focused ultrasound (FUS) with a focal diameter of 100 µm, which ejects droplets capable of extracting and transferring only the targeted cell(s) from a monolayer. RESULTS: The extraction and collection of 1-10 cells are successfully demonstrated. The number of ejected cells can be controlled by the FUS pulse width. As confirmed by fluorescence-based cell viability assays and re-culture experiments, the ejected cell(s) and remaining monolayer cells are intact without damage after cell ejection. Furthermore, real-time reverse transcription polymerase chain reaction (RT-PCR) tests for both housekeeping genes (GAPDH and ß -actin) and RPE-specific genes (MITF, PEDF, and PMEL17) show no significant difference between the acoustically ejected cells and those collected manually with a micropipette. CONCLUSION: The proposed technology realizes a contactless, damage-free extraction of cells with high spatial resolution and precise control of the number of cells ejected, with a simple setup. SIGNIFICANCE: This powerful technology not only enables efficient, high-precision cell extraction for quality check applications but also opens new avenues for other advanced biotechnologies such as bioprinting.

Understanding the Response of Poly(ethylene glycol) diacrylate (PEGDA) Hydrogel Networks: A Statistical Mechanics-Based Framework.

Thanks to many promising properties, including biocompatibility and the ability to experience large deformations, poly(ethylene glycol) diacrylate (PEGDA) hydrogels are excellent candidate materials for a wide range of applications. Interestingly, the polymerization of PEGDA leads to a network microstructure that is fundamentally different from that of the "classic" polymeric gels. Specifically, PEGDA hydrogels comprise PEG chains that are interconnected by multifunctional densely grafted rod-like polyacrylates (PAs), which serve as cross-linkers. In this work, we derive a microstructurally motivated model that captures the essential features which enable deformation in PEGDA hydrogels: (1) entropic elasticity of PEG chains, (2) deformation of PA rods, and (3) PA-PA interactions. Expressions for the energy-density functions and the stress associated with each of the three contributions are derived. The model demonstrates the microstructural evolution of the network during loading and reveals the role of key microscopic quantities. To validate the model, we fabricate and compress PEGDA hydrogel discs. The model is in excellent agreement with our experimental findings for a broad range of PEGDA compositions. Interestingly, we show that the response of PEGDA hydrogels with short PEG chains and long PA rods is governed by PA-PA interactions, whereas networks with longer PEG chains are dominated by entropy. To enable design, we employ the model to investigate the influence of key microstructural quantities, such as the length of the PEG and the PA chains, on the macroscopic properties and response. The findings from this work pave the way to the efficient design of PEGDA hydrogels with tunable properties and behaviors, which will enable the optimization of their performance in various applications.

Simple sacrificial-layer-free microfabrication processes for air-cavity Fresnel acoustic lenses (ACFALs) with improved focusing performance.

Focused ultrasound (FUS) is a powerful tool widely used in biomedical therapy and imaging as well as in sensors and actuators. Conventional focusing techniques based on curved surfaces, metamaterial structures, and multielement phased arrays either present difficulties in massively parallel manufacturing with high precision or require complex drive electronics to operate. These difficulties have been addressed by microfabricated self-focusing acoustic transducers (SFATs) with Parylene air-cavity Fresnel acoustic lenses (ACFALs), which require a time-demanding step in removing the sacrificial layer. This paper presents three new and improved types of ACFALs based on polydimethylsiloxane (PDMS), an SU-8/PDMS bilayer, and SU-8, which are manufactured through simple sacrificial-layer-free microfabrication processes that are two to four times faster than that for the Parylene ACFALs. Moreover, by studying the effect of the lens thickness on the acoustic transmittance through the lens, the performance of the transducers has been optimized with improved thickness control techniques developed for PDMS and SU-8. As a result, the measured power transfer efficiency (PTE) and peak output acoustic pressure are up to 2.0 and 1.8 times higher than those of the Parylene ACFALs, respectively. The simple microfabrication techniques described in this paper are useful for manufacturing not only high-performance ACFALs but also other miniaturized devices with hollow or suspended structures for microfluidic and optical applications.

In Vivo Non-Thermal, Selective Cancer Treatment With High-Frequency Medium-Intensity Focused Ultrasound.

Focused ultrasound (FUS) has proven its efficacy in non-invasive, radiation-free cancer treatment. However, the commonly used low-frequency high-intensity focused ultrasound (HIFU) destroys both cancerous and healthy tissues non-specifically through extreme heat and inertial cavitation with low spatial resolution. To address this issue, we evaluate the therapeutic effects of pulsed (60 Hz pulse repetition frequency, 1.45 ms pulse width) high-frequency (20.7 MHz) medium-intensity (spatial-peak pulse-average intensity ISPPA < 279.1 W/cm2, spatial-peak temporal-average intensity ISPTA < 24.3 W/cm2) focused ultrasound (pHFMIFU) for selective cancer treatment without thermal damage and with low risk of inertial cavitation (mechanical index < 0.66), in an in vivo subcutaneous B16F10 melanoma tumor growth model in mice. The pHFMIFU with 104 µm focal diameter is generated by a microfabricated self-focusing acoustic transducer (SFAT) with a Fresnel acoustic lens. A three-axis positioning system has been developed for automatic scanning of the transducer to cover a larger treatment volume, while a water-cooling system is custom-built for dissipating non-acoustic heat from the transducer surface. Initial testing revealed that pHFMIFU treatment can be applied to a living animal while maintaining skin temperature under 35.6 °C without damaging normal skin and tissue. After eleven days of treatment with pHFMIFU, the treated tumors were significantly smaller with large areas of necrosis and apoptosis in the treatment field compared to untreated controls. Potential mechanisms of this selective, non-thermal killing effect, as well as possible causes of and solutions to the variation in treatment results, have been analyzed and proposed. The pHFMIFU could potentially be used as a new therapeutic modality for safer cancer treatment especially in critical body regions, due to its cancer-specific effects and high spatial resolution.