Integrated "lab-on-a-chip" microfluidic systems for isolation, enrichment, and analysis of cancer biomarkers.

The liquid biopsy has garnered considerable attention as a complementary clinical tool for the early detection, molecular characterization and monitoring of cancer over the past decade. In contrast to traditional solid biopsy techniques, liquid biopsy offers a less invasive and safer alternative for routine cancer screening. Recent advances in microfluidic technologies have enabled handling of liquid biopsy-derived biomarkers with high sensitivity, throughput, and convenience. The integration of these multi-functional microfluidic technologies into a 'lab-on-a-chip' offers a powerful solution for processing and analyzing samples on a single platform, thereby reducing the complexity, bio-analyte loss and cross-contamination associated with multiple handling and transfer steps in more conventional benchtop workflows. This review critically addresses recent developments in integrated microfluidic technologies for cancer detection, highlighting isolation, enrichment, and analysis strategies for three important sub-types of cancer biomarkers: circulating tumor cells, circulating tumor DNA and exosomes. We first discuss the unique characteristics and advantages of the various lab-on-a-chip technologies developed to operate on each biomarker subtype. This is then followed by a discussion on the challenges and opportunities in the field of integrated systems for cancer detection. Ultimately, integrated microfluidic platforms form the core of a new class of point-of-care diagnostic tools by virtue of their ease-of-operation, portability and high sensitivity. Widespread availability of such tools could potentially result in more frequent and convenient screening for early signs of cancer at clinical labs or primary care offices.

Analysis and Design of Capacitive Parametric Ultrasonic Transducers for Efficient Ultrasonic Power Transfer Based on a 1-D Lumped Model.

There is an increasing interest in wireless power transfer for medical implants, sensor networks, and consumer electronics. A passive capacitive parametric ultrasonic transducer (CPUT) can be suitable for these applications as it does not require a dc bias or a permanent charge. In this paper, we present a 1-D lumped parameter model of the CPUT to study its operation and investigate relevant design parameters for power transfer applications. The CPUT is modeled as an ultrasound-driven piston coupled to an RLC resonator resulting in a system of two coupled nonlinear ordinary differential equations. Simulink is used along with an analytical approximation of the system to obtain the voltage across the capacitor and displacement of the piston. Parametric resonance threshold and ultrasound-to-electrical conversion efficiency are evaluated, and the dependence of these performance metrics on the load resistance, input ultrasound intensity, forcing frequency, electrode coverage area, gap height, and the mechanical Q-factor are studied. Based on this analysis, design guidelines are proposed for highly efficient power transfer. Guided by these results, practical device designs are obtained through COMSOL simulations. Finally, the feasibility of using the CPUT in air is predicted to set the foundation for further research in ultrasonic wireless power transfer, energy harvesting, and sensing.

A capacitive ultrasonic transducer based on parametric resonance.

A capacitive ultrasonic transducer based on a parametric resonator structure is described and experimentally demonstrated. The transducer structure, which we call capacitive parametric ultrasonic transducer (CPUT), uses a parallel plate capacitor with a movable membrane as part of a degenerate parametric series RLC resonator circuit with a resonance frequency of fo. When the capacitor plate is driven with an incident harmonic ultrasonic wave at the pump frequency of 2fo with sufficient amplitude, the RLC circuit becomes unstable and ultrasonic energy can be efficiently converted to an electrical signal at fo frequency in the RLC circuit. An important characteristic of the CPUT is that unlike other electrostatic transducers, it does not require DC bias or permanent charging to be used as a receiver. We describe the operation of the CPUT using an analytical model and numerical simulations, which shows drive amplitude dependent operation regimes including parametric resonance when a certain threshold is exceeded. We verify these predictions by experiments with a micromachined membrane based capacitor structure in immersion where ultrasonic waves incident at 4.28 MHz parametrically drive a signal with significant amplitude in the 2.14 MHz RLC circuit. With its unique features, the CPUT can be particularly advantageous for applications such as wireless power transfer for biomedical implants and acoustic sensing.