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Solid-State Microfluidics with Integrated Thin-Film Acoustic Sensors

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Abstract

For point-of-care applications, integrating sensors into a microfluidic chip is a nontrivial task, since conventional detection modules are bulky and microfluidic chips are small in size, and their fabrication processes are not compatible. In this work, a solid-state microfluidic chip with on-chip acoustic sensors using standard thin-film technologies is introduced. The integrated chip is essentially a stack of thin films on silicon substrate, featuring compact size, electrical input (fluid control) and electrical output (sensor read-out). These features all contribute to portability. In addition, by virtue of processing discrete micro-droplets, the chip provides a solution to the performance degradation bottleneck of acoustic sensors in liquid-phase sensing. Label-free immunoassays in serum are carried out and the viability of the chip is further demonstrated by result comparison with commercial ELISA in prostate-specific antigen sensing experiments. The solid-state chip is believed to fit specific applications in personalized diagnostics and other relevant clinical settings where instrument portability matters.

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The ambition of lab-on-a-chip (LOC) systems to achieve chip-level integration of a complete analytical process capable of performing a complex set of biomedical protocols is hindered by the absence of standard fluidic components able to be assembled. As a result, most microfluidic platforms built to date are highly specialized and designed to fulfill the requirements of a single particular application within a limited set of operations. Electrowetting-on-dielectric (EWOD) digital microfluidic technology has been recently introduced as a new methodology in the quest for LOC systems. Herein, unit volume droplets are manipulated along electrode arrays, allowing a microfluidic function to be reduced to a set of basic operations. The highly reprogrammable architecture of these systems can satisfy the needs of a diverse set of biochemical assays and ensure reconfigurability, flexibility and portability between different categories of applications and requirements. While important progress was made over past years in the fabrication, miniaturization and function programming of the basic EWOD fluidic operations, the success of this technology will in great part depend on the ability of researchers to couple or integrate digital microfluidics to detection approaches that can make the system competitive for LOC applications. The detection techniques should be able to circumvent the limitations of hydrophobic surfaces and exploit the advantages of the array format, high droplet transport speeds and rapid mixing schemes. This review provides an in-depth look at recent developments for the coupling and integration of detection techniques with digital microfluidic platforms for bio-chemical applications.
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Voltage pulses that cause changes in fluid shape or movement can be used to drive optical components and miniaturized assays.
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We describe devices in which optics and fluidics are used synergistically to synthesize novel functionalities. Fluidic replacement or modification leads to reconfigurable optical systems, whereas the implementation of optics through the microfluidic toolkit gives highly compact and integrated devices. We categorize optofluidics according to three broad categories of interactions: fluid-solid interfaces, purely fluidic interfaces and colloidal suspensions. We describe examples of optofluidic devices in each category.
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To realize multiplexed sample preparation on a digital microfluidic chip for high-throughput Matrix Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-MS), several fluidic functions need to be integrated. These include the generation of multiple droplets from a reservoir and parallel in-line sample purification. In this paper, we develop two critical new functions in handling protein solutions and standard proteomic reagents with electrowetting-on-dielectric (EWOD) actuation, leading to an integrated chip for multiplexed sample preparation for MALDI-MS. The first is a voltage sequence designed to generate a series of droplets from each of the three reservoirs--proteomic sample, rinsing fluid, and MALDI reagents. It is the first time that proteomic reagents have been dispensed using EWOD in an air (as opposed to oil) environment. The second is a box-in-box electrode pattern developed to allow droplet passing over dried sample spots, making the process of in-line sample purification robust for parallel processing. As a result, parallel processing of multiple sample droplets is demonstrated on the integrated EWOD-MALDI-MS chip, an important step towards high-throughput MALDI-MS. The MS results, collected directly from the integrated devices, are of good quality, suggesting that the tedious process of sample preparation can be automated on-chip for MALDI-MS applications as well as other high-throughput proteomics applications.
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A full-field view laser ultrasonic imaging method has been developed that measures acoustic motion at a surface without scanning. Images are recorded at normal video frame rates by using dynamic holography with photorefractive interferometric detection. By extending the approach to ultra high frequencies, an acoustic microscope has been developed that is capable of operation at gigahertz frequency and micron length scales. Both acoustic amplitude and phase are recorded, allowing full calibration and determination of phases to within a single arbitrary constant. Results are presented of measurements at frequencies of 800-900 MHz, illustrating a multitude of normal mode behavior in electrically driven thin film acoustic resonators. Coupled with microwave electrical impedance measurements, this imaging mode provides an exceptionally fast method for evaluation of electric-to-acoustic coupling of these devices and their performance. Images of 256 /spl times/ 240 pixels are recorded at 18 fps rates synchronized to obtain both in-phase and quadrature detection of the acoustic motion. Simple averaging provides sensitivity to the subnanometer level at each pixel calibrated over the image using interferometry. Identification of specific acoustic modes and their relationship to electrical impedance characteristics show the advantages and overall high speed of the technique.