Developing a surface acoustic wave-induced microfluidic cell lysis device for point-of-care DNA amplification.

We developed a microchip device using surface acoustic waves (SAW) and sharp-edge glass microparticles to rapidly lyse low-level cell samples. This microchip features a 13-finger pair interdigital transducer (IDT) with a 30-degree focused angle, creating high-intensity acoustic beams converging 6 mm away at a 16 MHz frequency. Cell lysis is achieved through centrifugal forces acting on Candida albicans cells and glass particles within the focal area. To optimize this SAW-induced streaming, we conducted 42 pilot experiments, varying electrical power, droplet volume, glass particle size, concentration, and lysis time, resulting in optimal conditions: an electrical signal of 2.5 W, a 20 µL sample volume, glass particle size below 10 µm, concentration of 0.2 µg, and a 5-min lysis period. We successfully amplified DNA target fragments directly from the lysate, demonstrating an efficient microchip-based cell lysis method. When combined with an isothermal amplification technique, this technology holds promise for rapid point-of-care (POC) applications.

A urinary Bcl-2 surface acoustic wave biosensor for early ovarian cancer detection.

In this study, the design, fabrication, surface functionalization and experimental characterization of an ultrasonic MEMS biosensor for urinary anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) detection with sub ng/mL sensitivity is presented. It was previously shown that urinary Bcl-2 levels are reliably elevated during early and late stages of ovarian cancer. Our biosensor uses shear horizontal (SH) surface acoustic waves (SAWs) on surface functionalized ST-cut Quartz to quantify the mass loading change by protein adhesion to the delay path. SH-SAWs were generated and received by a pair of micro-fabricated interdigital transducers (IDTs) separated by a judiciously designed delay path. The delay path was surface-functionalized with monoclonal antibodies, ODMS, Protein A/G and Pluronic F127 for optimal Bcl-2 capture with minimal non-specific adsorption. Bcl-2 concentrations were quantified by the resulting resonance frequency shift detected by a custom designed resonator circuit. The target sensitivity for diagnosis and identifying the stage of ovarian cancer was successfully achieved with demonstrated Bcl-2 detection capability of 500 pg/mL. It was also shown that resonance frequency shift increases linearly with increasing Bcl-2 concentration.

An analog integrated circuit beamformer for high-frequency medical ultrasound imaging.

We designed and fabricated a dynamic receive beamformer integrated circuit (IC) in 0.35-µm CMOS technology. This beamformer IC is suitable for integration with an annular array transducer for high-frequency (30-50 MHz) intravascular ultrasound (IVUS) imaging. The beamformer IC consists of receive preamplifiers, an analog dynamic delay-and-sum beamformer, and buffers for 8 receive channels. To form an analog dynamic delay line we designed an analog delay cell based on the current-mode first-order all-pass filter topology, as the basic building block. To increase the bandwidth of the delay cell, we explored an enhancement technique on the current mirrors. This technique improved the overall bandwidth of the delay line by a factor of 6. Each delay cell consumes 2.1-mW of power and is capable of generating a tunable time delay between 1.75 ns to 2.5 ns. We successfully integrated the fabricated beamformer IC with an 8-element annular array. Experimental test results demonstrated the desired buffering, preamplification and delaying capabilities of the beamformer.