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Micromanipulation of Particles and Cells Using Ultrasound
The contactless handling of micro-particles and cells bypasses the problems of adhesion and possible damage to microstructures incurred by contact methods such as miniature tweezers. The principle of using ultrasound to position particles and cells (10 to 100μm) in 3-D has been demonstrated. A device has been designed, theoretically described, and experimentally verified, for this task. The device consists of two plates, one active and one passive, between which a fluid layer (typically 500 to 1000μm thick) containing the suspended particles is trapped, as can be seen in the figure.
Fig. 1 Glass plate device
The active plate is a 12 mm square piece of glass with shear piezoelectric elements attached at each edge. When excited these piezoelectric elements cause a periodic surface displacement of the plate. This displacement causes the propagation of acoustic waves in the fluid layer which are reflected by the passive plate (usually a glass slide). The result is a 2 or 3 dimensional standing pressure field in the fluid, depending on whether the active plate is excited by one or two orthogonally orientated piezoelectric elements, respectively. The presence of the pressure field causes a force field capable of collecting particles or cells at the potential minima, and so into lines or points. Depending on the geometry of the system, this can involve the levitation of the particles from the lower surface.
Fig. 2 Positioning of MCF10A cells in lines. Images taken at 0 s, 0.8 s and 1.6 s (Haake et al, Biotechnology and Bioengineering 92, 2005).
Fig. 3 Positioning of HeLa cells at points. Images taken at 0 s, 2 s and 4 s (Haake et al, Biotechnology and Bioengineering 92, 2005).
Furthermore, it is possible to subsequently displace the cells with micrometer accuracy, by altering the sound field. Due to the relative size of the spatial periodicity of the ultrasound field and the particle size, this method, unlike optical systems, is capable of handling many particles simultaneously. In addition as the force field acts across the whole fluid layer it is not necessary to first locate particles prior to manipulation. Further information (video) here.
The device consists of 200 µm deep, 5 mm wide channel which was etched into a 300 µm thick Si wafer, the length differing from device to device (typical value 5 mm). A glass plate and piezoelectric plate were attached to the Si layer.
Fig. 4 Microfluidic channel device
The upper electrode and the larger lower electrode were grounded, and the signal applied to a 0.7 mm wide electrode strip along the edge of the lower electrode. When a sinusoidal voltage is applied, a wave propagates along the piezoelectric plate from the activated end. The resultant vibration couples to the fluid layer to create a pressure field, which, when the appropriate frequency is used, is capable of aligning particles suspended in the fluid volume. The device is supported at each end.
A method for two dimensional arraying based on the superposition of two in-plane orthogonally oriented standing pressure waves has been investigated. A device has been built (Fig. 5) and the experimental results have been compared with a qualitative analytical model. A single piezoelectric transducer is used to excite the structure to vibration, which consists of a square chamber etched in silicon sealed with a glass plate. A set of orthogonally aligned electrodes, analogously to the strip electrodes mentioned above, have been defined on one surface of the piezoelectric. This allows either a quasi one dimensional standing pressure field to be excited in one of two directions or if both electrodes are activated simultaneously a two dimensional pressure field to be generated.
Fig. 5 Device for 2D positioning
Two different operational modes have been studied: two signals identical in amplitude and frequency were used to trap particles in oval shaped clumps; two signals with slightly different frequencies to trap particles in circular clumps (Fig. 6).
Fig. 6 Two different patterns can be achieved, depending on the difference between the excitation frequencies.
Recently the feasibility of the combined use of different manipulations techniques, in particular acoustic manipulation and mechanical gripping, has been investigated. Particles previously aligned along the centerline of a 1mm wide, 200 mm deep channel have been removed by means of a microgripper inserted trough an interface on the side. It has been shown that the accuracy and repeatability of the lateral positioning is sufficient to operate the microgripper in such a way that it does not need to be moved laterally.
Video 1: Combined use of acoustic manipulation and mechanical gripping
Collaboration with the group of Prof. B. Nelson, www.iris.ethz.ch (funded by KTI, TopNano 21 Number 6643.1 and 6989.1).
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Glass
plate device
