The precise rotational manipulation of single cells or organisms is invaluable to many applications in biology, chemistry, physics and medicine. In this article, we describe an acoustic-based, on-chip manipulation method that can rotate single microparticles, cells and organisms. To achieve this, we trapped microbubbles within predefined sidewall microcavities inside a microchannel. In an acoustic field, trapped microbubbles were driven into oscillatory motion generating steady microvortices which were utilized to precisely rotate colloids, cells and entire organisms (that is, C. elegans). We have tested the capabilities of our method by analysing reproductive system pathologies and nervous system morphology in C. elegans. Using our device, we revealed the underlying abnormal cell fusion causing defective vulval morphology in mutant worms. Our acoustofluidic rotational manipulation (ARM) technique is an easy-to-use, compact, and biocompatible method, permitting rotation regardless of optical, magnetic or electrical properties of the sample under investigation.

Rotational manipulation of single cells and organisms using acoustic waves

Many applications of ultrasound for sensing, actuation and imaging require miniaturized and low power transducers and transducer arrays integrated with electronic systems. Piezoelectric micromachined ultrasound transducers (PMUTs), diaphragm-like thin film flexural transducers typically formed on silicon substrates, are a potential solution for integrated transducer arrays. This paper presents an overview of the current development status of PMUTs and a discussion of their suitability for miniaturized and integrated devices. The thin film piezoelectric materials required to functionalize these devices are discussed, followed by the microfabrication techniques used to create PMUT elements and the constraints the fabrication imposes on device design. Approaches for electrical interconnection and integration with on-chip electronics are discussed. Electrical and acoustic measurements from fabricated PMUT arrays with up to 320 diaphragm elements are presented. The PMUTs are shown to be broadband devices with an operating frequency which is tunable by tailoring the lateral dimensions of the flexural membrane or the thicknesses of the constituent layers. Finally, the outlook for future development of PMUT technology and the potential applications made feasible by integrated PMUT devices are discussed.

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Piezoelectric Micromachined Ultrasound Transducer (PMUT) Arrays for Integrated Sensing, Actuation and Imaging

New developments in the microrheology of complex fluids are considered. Firstly the requirements for a simple modern particle tracking microrheology experiment are introduced, the error analysis methods associated with it and the mathematical techniques required to calculate the linear viscoelasticity. Progress in microrheology instrumentation is then described with respect to detectors, light sources, colloidal probes, magnetic tweezers, optical tweezers, diffusing wave spectroscopy, optical coherence tomography, fluorescence correlation spectroscopy, elastic- and quasi-elastic scattering techniques, 3D tracking, single molecule methods, modern microscopy methods and microfluidics. New theoretical techniques are also reviewed such as Bayesian analysis, oversampling, inversion techniques, alternative statistical tools for tracks (angular correlations, first passage probabilities, the kurtosis, motor protein step segmentation etc), issues in micro/macro rheological agreement and two particle methodologies. Applications where microrheology has begun to make some impact are also considered including semi-flexible polymers, gels, microorganism biofilms, intracellular methods, high frequency viscoelasticity, comb polymers, active motile fluids, blood clots, colloids, granular materials, polymers, liquid crystals and foods. Two large emergent areas of microrheology, non-linear microrheology and surface microrheology are also discussed.

https://iopscience.iop.org/article/10.1088/0034-4885/79/7/074601/pdf

Advances in the microrheology of complex fluids.

Acoustic actuation of bioinspired microswimmers is experimentally demonstrated. Microswimmers are fabricated in situ in a microchannel. Upon acoustic excitation, the flagellum of the microswimmer oscillates, which in turn generates linear or rotary movement depending on the swimmer design. The speed of these bioinspired microswimmers is tuned by adjusting the voltage amplitude applied to the acoustic transducer. Simple microfabrication and remote actuation are promising for biomedical applications.

Acoustic actuation of bioinspired microswimmers

Optical manipulations utilizing the mechanical effect of light have been indispensable in various disciplines. Among those various manipulations, optical pulling has emerged recently as an attractive notion and captivated the popular imagination, not only because it constitutes a rich family of counterintuitive phenomena compared with traditional manipulations but also due to the profound physics underneath and potential applications. Beginning with a general introduction to optical forces, related theories, and methods, we review the progresses achieved in optical pulling forces using different mechanisms and configurations. Similar pulling forces in other forms of waves, including acoustic, water, and quantum matter waves, are also integrated. More importantly, we also include the progresses in counterintuitive left-handed optical torque and lateral optical force as the extensions of the pulling force. As a new manipulation degree of freedom, optical pulling force and related effects have potential applications in remote mass transportation, optical rotating, and optical sorting. They may also stimulate the investigations of counterintuitive phenomena in other forms of waves.

Optical pulling forces and their applications

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.

Acoustic Devices for Particle and Cell Manipulation and Sensing

Ultrasonic standing wave manipulation has many promising applications in cell biology, such as noncontact investigation of cell and tissue mechanics. In this paper, recent progress in developing a high frequency resonant chamber using a lithium niobate transducer is presented. This device is designed to sit on a petri dish or microscope slide, with the propagation direction parallel to the dish surface, in a configuration compatible with an optical microscope. It comprises a high frequency ultrasonic transducer with a low acoustic impedance transducer mounting, a polished reflector, and a set of precision spacers between the reflector and transducer. The prototype device demonstrates the feasibility of trapping microparticles with ultrasound radiation forces in multiple trapping sites, and the short wavelength reduces the separation of trapping sites to the same order as the cell dimensions. The basic design of device was validated with one dimensional modelling and finite element simulation. Experimental results of trapping 10 μm polystyrene beads correspond to simulated pressure distributions showing multiples of half-wavelength standing waves.

Kees Weijer

Papers

Acoustic Devices for Particle and Cell Manipulation and Sensing

Multi-wavelength ultrasonic standing wave device for non-invasive cell manipulation and characterisation