Abstract

An emerging demand for the precise manipulation of cells and particles for applications in cell biology and analytical chemistry has driven rapid development of ultrasonic manipulation technology. Compared to the other manipulation technologies, such as magnetic tweezing, dielectrophoresis and optical tweezing, ultrasonic manipulation has shown potential in a variety of applications, with its advantages of versatile, inexpensive and easy integration into microfluidic systems, maintenance of cell viability, and generation of sufficient forces to handle particles, cells and their agglomerates. This article briefly reviews current practice and reports our development of various ultrasonic standing wave manipulation devices, including simple devices integrated with high frequency (>20 MHz) ultrasonic transducers for the investigation of biological cells and complex ultrasonic transducer array systems to explore the feasibility of electronically controlled 2-D and 3-D manipulation. Piezoelectric and passive materials, fabrication techniques, characterization methods and possible applications are discussed. The behavior and performance of the devices have been investigated and predicted with computer simulations, and verified experimentally. Issues met during development are highlighted and discussed. To assist long term practical adoption, approaches to low-cost, wafer level batch-production and commercialization potential are also addressed.

Highlights

  • In recent decades, precise control of bioparticles, biomolecules and biological cells has become increasingly important in life sciences and medicine, with applications emerging in fields such as biochemical analysis, cell separation and sorting, study of cell mechanisms, and tissue engineering.Following this demand, particle manipulation technologies have been developing actively.One existing approach is to utilize contact-mediated forces applied to targets directly by mechanical tools, e.g., micropipettes [1], atomic force microscopes [2] and micro-grippers [3]

  • With the motivations to overcome the limitations of ultrasonic manipulation (USM) devices in terms of: (1) forces that can be generated; (2) constrained trapping sites due to the enclosure resonances and geometry of the devices; and (3) fabrication complexities negatively affecting progress towards mass production and commercialization, several multilayer resonator type USM devices have been investigated through simulation and experiment

  • The weak acoustic radiation forces generated in the current prototype device, still somewhat constrained cell motility

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Summary

Introduction

Precise control of bioparticles, biomolecules and biological cells has become increasingly important in life sciences and medicine, with applications emerging in fields such as biochemical analysis, cell separation and sorting, study of cell mechanisms, and tissue engineering.Following this demand, particle manipulation technologies have been developing actively.One existing approach is to utilize contact-mediated forces applied to targets directly by mechanical tools, e.g., micropipettes [1], atomic force microscopes [2] and micro-grippers [3]. Precise control of bioparticles, biomolecules and biological cells has become increasingly important in life sciences and medicine, with applications emerging in fields such as biochemical analysis, cell separation and sorting, study of cell mechanisms, and tissue engineering Following this demand, particle manipulation technologies have been developing actively. Direct mechanical intervention can cause problems with mechanical damage to the fragile structure of cells or tissues, and difficulty in handling large numbers of targets Contactless micromanipulation techniques, such as magnetic tweezing (MT) [4], dielectrophoresis (DEP) [5], optical tweezing (OT) [6], and ultrasonic manipulation (USM) [7] have significant advantages, creating moderate forces to drive particles towards equilibrium states at local potential energy minima without any direct, physical contact. Attention has been given to combining multiple contactless techniques in single systems, taking advantage of the particular properties of each technique, e.g., integrating USM and DEP [8], and USM and OT [9,10] to achieve precise manipulation of individual cells whilst simultaneously maintaining high throughput

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