Yongqiang Qiu

Array-controlled ultrasonic manipulation of particles in planar acoustic resonator

Ultrasonic particle manipulation tools have many promising applications in life sciences, expanding on the capabilities of current manipulation technologies. In this paper, the ultrasonic manipulation of particles and cells along a microfluidic channel with a piezoelectric array is demonstrated. An array integrated into a planar multilayer resonator structure drives particles toward the pressure nodal plane along the centerline of the channel, then toward the acoustic velocity maximum centered above the subset of elements that are active. Switching the active elements along the array moves trapped particles along the microfluidic channel. A 12-element 1-D array coupled to a rectangular capillary has been modeled and fabricated for experimental testing. The device has a 300-μm-thick channel for a half-wavelength resonance near 2.5 MHz, with 500 μm element pitch. Simulation and experiment confirm the expected trapping of particles at the center of the channel and above the set of active elements. Experiments demonstrated the feasibility of controlling the position of particles along the length of the channel by switching the active array elements.

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

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.

Letters: optically transparent piezoelectric transducer for ultrasonic particle manipulation

We report an optically transparent ultrasonic device, consisting of indium-tin-oxide-coated lithium niobate (LNO), for use in particle manipulation. This device shows good transparency in the visible and near-infrared wavelengths and, acoustically, compares favorably with conventional prototype devices with silver electrodes.

Acoustic devices for particle and cell manipulation and sensing.

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.

Transducer arrays for ultrasonic particle manipulation

Ultrasonic particle manipulation tools have many promising applications in life sciences research, expanding on the capabilities of current manipulation technologies. In this paper the feasibility of ultrasonic manipulation of particles and cells along a microfluidic channel with an array is investigated. An array integrated into a multilayer resonator structure drives particles towards the pressure nodal plane along the axis of the channel, then towards the acoustic velocity maximum centered above the driven elements. Switching the active elements along the array moves trapped particles along the microfluidic channel. A 1-D array coupled to a rectangular capillary has been simulated and fabricated for experimental testing. The device has a 300 µm thick channel for a half wavelength resonance near 2.5 MHz, and 500 µm element pitch. Simulation and experiment confirm the expected trapping of particles at the centre of the channel and above the set of driven elements. Experiments demonstrated the feasibility of controlling the position of particles along the length of the channel by switching the driven array elements.

Micromachined diaphragm transducers for miniaturised ultrasound arrays

Miniaturised ultrasound transducer arrays with integrated electronics will in future enable significant advances in high resolution medical imaging and in acoustic tweezing for bioscience research. However, their development has been limited by challenges in scaling down conventional piezoelectric ultrasound transducer fabrication and interconnection techniques. Piezoelectric thin film transducers on silicon substrates can overcome these challenges by reducing dimensional constraints in fabrication and facilitating integration with electronics, including allowing low drive voltages in transmission. We present the design, fabrication and testing of diaphragm transducers to evaluate the feasibility of integrated piezoelectric micromachined ultrasonic transducers (PMUTs). Transducers have been designed, then fabricated with 80 μm and 130 μm diameter diaphragms, the latter in arrays with ~500 diaphragms. Receive measurements demonstrate functionality of both devices, with pulse-echo bandwidths of approximately 90% for the 80 μm diaphragms, demonstrating initial feasibility for ultrasound imaging.

Screen-printed ultrasonic 2-D matrix array transducers for microparticle manipulation

This paper reports the development of a two-dimensional thick film lead zirconate titanate (PZT) ultrasonic transducer array, operating at frequency approximately 7.5MHz, to demonstrate the potential of this fabrication technique for microparticle manipulation. All layers of the array are screen-printed then sintered on an alumina substrate without any subsequent patterning processes. The thickness of the thick film PZT is 139±2μm, the element pitch of the array is 2.3mm, and the dimension of each individual PZT element is 2×2mm(2) with top electrode 1.7×1.7mm(2). The measured relative dielectric constant of the PZT is 2250±100 and the dielectric loss is 0.09±0.005 at 10kHz. Finite element analysis was used to predict the behaviour of the array and to optimise its configuration. Electrical impedance spectroscopy and laser vibrometry were used to characterise the array experimentally. The measured surface motion of a single element is on the order of tens of nanometres with a 10Vpeak continuous sinusoidal excitation. Particle manipulation experiments have been demonstrated with the array by manipulating Ø10μm polystyrene microspheres in degassed water. The simplified array fabrication process and the bulk production capability of screen-printing suggest potential for the commercialisation of multilayer planar resonant devices for ultrasonic particle manipulation.

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

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.

Acoustic Sensing and Ultrasonic Drug Delivery in Multimodal Theranostic Capsule Endoscopy

Video capsule endoscopy (VCE) is now a clinically accepted diagnostic modality in which miniaturized technology, an on-board power supply and wireless telemetry stand as technological foundations for other capsule endoscopy (CE) devices. However, VCE does not provide therapeutic functionality, and research towards therapeutic CE (TCE) has been limited. In this paper, a route towards viable TCE is proposed, based on multiple CE devices including important acoustic sensing and drug delivery components. In this approach, an initial multimodal diagnostic device with high-frequency quantitative microultrasound that complements video imaging allows surface and subsurface visualization and computer-assisted diagnosis. Using focused ultrasound (US) to mark sites of pathology with exogenous fluorescent agents permits follow-up with another device to provide therapy. This is based on an US-mediated targeted drug delivery system with fluorescence imaging guidance. An additional device may then be utilized for treatment verification and monitoring, exploiting the minimally invasive nature of CE. While such a theranostic patient pathway for gastrointestinal treatment is presently incomplete, the description in this paper of previous research and work under way to realize further components for the proposed pathway suggests it is feasible and provides a framework around which to structure further work.

Investigating the motility of Dictyostelium discodeum using high frequency ultrasound as a method of manipulation

Cell motility is an essential process in the development of all organisms. The earliest stages of embryonic development involve massive reconfigurations of groups of cells to form the early body structures. Embryos are very complex systems, and therefore to investigate the molecular and cellular basis of development a simpler genetically tractable model system is used. The social amoeba Dictyostelium Discoideum is known to chemotax up a chemical gradient. From previous work, it is clear that cells generate forces in the nN range. This is above the limit of optical tweezers and therefore we are investigating the use of acoustic tweezers instead. In this paper, we present recent progress of the investigation in to the use of acoustic tweezers for the characterisation of cell motility and forces. We will describe the design, modelling and fabrication of several devices. All devices use high frequency (>15MHz) ultrasound to exert a force on the cells to position and/or stall them. Also, each device is designed to be suitable for the life-sciences laboratory where form-factor and sterility is concerned. A transducer (LiNo) operating at 24 MHz excites resonant acoustic modes in a rectangular glass capillary (100um by 2mm). This device is used to alter the directionality of the motile cells inside the fluid filled capillary. A quarter-ring PZT26 transducer operating at 20.5MHz is shown to be useful for manipulating cells using axial acoustic radiation forces. This device is used to exert a force on cells and shown to pull them away from a coverslip. The presented devices show promise for the manipulation of cells in suspension. Currently the forces produced are below that required for adherent cells; the reasons for this are discussed. We also report on other issues that arise when using acoustic waves for manipulating biological samples such as streaming and heating.