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.
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.
With many emerging applications such as chemical reactions and ultrasound therapy, acoustic cavitation plays a vital role in having improved energy efficiency. For example, acoustic cavitation results in substantial enhancement in the rates of various chemical reactions. In this regard, an applied acoustic field within a medium generates acoustic streaming, where cavitation bubbles appear due to preexisting dissolved gas in the working fluid. Upon cavitation inception, bubbles can undergo subsequent growth and collapse. During the last decade, the studies on the effects of different parameters on acoustic cavitation such as applied ultrasound frequency and power have been conducted. The bubble growth and collapse mechanisms and their distribution within the medium have been classified. Yet, more research is necessary to understand the complex mechanism of multi-bubble behavior under an applied acoustic field. Various parameters affecting acoustic cavitation such as surface roughness of the acoustic generator should be investigated in more detail in this regard. In this study, single bubble lifetime, bubble size and multi-bubble dynamics were investigated by changing the applied ultrasonic field. The effect of surface roughness on bubble dynamics was presented. In the analysis, images from a high-speed camera and fast video recording techniques were used. Numerical simulations were also done to investigate the effect of acoustic field frequency on bubble dynamics. Bubble cluster behavior and required minimum bubble size to be affected by the acoustic field were obtained. Numerical results suggested that bubbles with sizes of 50 µm or more could be aligned according to the radiation potential map, whereas bubbles with sizes smaller than 10 µm were not affected by the acoustic field. Furthermore, it was empirically proven that surface roughness has a significant effect on acoustic cavitation phenomena.
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