Micromachines, Volume 5, Issue 1 (March 2014) – 8 articles , Pages 1-115

Mini and micro robots, which can swim in an underwater environment, have drawn widespread research interests because of their potential applicability to the medical or biological fields, including delivery and transportation of bio-materials and drugs, bio-sensing, and bio-surgery. This paper reviews the recent ideas and developments of these types of self-propelling devices, ranging from the millimeter scale down to the micro and even the nano scale. Specifically, this review article makes an emphasis on various propulsion principles, including methods of utilizing smart actuators, external magnetic/electric/acoustic fields, bacteria, chemical reactions, etc. In addition, we compare the propelling speed range, directional control schemes, and advantages of the above principles. Full article

We present a single cell study of a highly effective Hog1 inhibitor. For this application, we used sequential treatment of a Saccharomyces cerevisiae cell array, with the Hog1 inhibitor and osmotic stress. For this purpose, a four-inlet microfluidic chamber with controlled introduction of two different cell strains within the same experimental setting and a subsequent rapid switching between treatments was designed. Multiple cell strains within the same experiment is a unique feature which is necessary for determining the expected absent cellular response. The nuclear translocation of the cytosolic MAPK, Hog1, was monitored by fluorescence imaging of Hog1-GFP on a single-cell level. An optical tweezers setup was used for controlled cell capture and array formation. Nuclear Hog1-GFP localization was impaired for treated cells, providing evidence of a congenial microfluidic setup, where the control cells within the experiments validated its appropriateness. The chamber enables multiple treatments with incubation times in the order of seconds and the possibility to remove either of the treatments during measurement. This flexibility and the possibility to use internal control cells ensures it a valuable scientific tool for unraveling the HOG pathway, similar signal transduction pathways and other biological mechanisms where temporal resolution and real time imaging is a prerequisite. Full article

The micro-conveyor is a 9 × 9 mm² manipulation surface able to move millimeter-sized planar objects in the four cardinal directions using air flows. Thanks to a specific design, the air flow comes through a network of micro-channels connected to an array of micro-nozzles. Thus, the micro-conveyor generates an array of tilted air jets that lifts and moves the object in the required direction. In this paper, we characterize the device for transport and positioning tasks and evaluate its performances in terms of speed, resolution and repeatability. We show that the micro-conveyor is able to move the object with a speed up to 137 mm · s^-1 in less than 100 ms whereas the positioning repeatability is around 17.7 μm with feedback control. The smallest step the object can do is 0.3 μm (positioning resolution). Moreover, we estimated thanks to a dynamic model that the speed could reach 456 mm· s^-1 if several micro-conveyors were used to form a conveying line. Full article

Pneumatic microvalves are widely used key components for automating liquid manipulation and flow control in microfluidics for more than one decade. Due to their robust operations and the ease of fabrication, tremendous microfluidic systems have been developed with the multiple microvalves for higher throughput and extended functionalities. Therefore, operation performance of the microvalves in the integrated microfluidic devices is crucial to the related applications, in fields such as micro-flows, cell analyses, drug discovery, and physical/chemical detections. It has been reported that operation performance of the microvalves are highly sensitive to the device configuration and pressurization scheme. This implies the further development of integrated microfluidics with a larger number of the valves may suffer the problems of undetermined microvalve behaviors during operations, which can become an unavoidable hurdle in the device design and optimization processes. Herein, we characterize responses of the individual microvalves for different operation configurations, e.g., membrane thicknesses and driving pressures. We investigate also the effects in microfluidics integrated with the more valves, through experiments, modeling and simulations. We show that dynamics of the microvalves is indeed influenced by the configurations, levels of design complexity and positions in the devices. Overall, taken dynamics of the microvalve responses into considerations, this work provides insights and guidelines for better designs of integrated microfluidics for the future applications requiring higher throughput and improved operation performance. Full article

This review describes the use of ultrasound for inducing and retaining cell-cell contact in multi-well microplates combined with live-cell fluorescence microscopy. This platform has been used for studying the interaction between natural killer (NK) cells and cancer cells at the level of individual cells. The review includes basic principles of ultrasonic particle manipulation, design criteria when building a multi-well microplate device for this purpose, biocompatibility aspects, and finally, two examples of biological applications: Dynamic imaging of the inhibitory immune synapse, and studies of the heterogeneity in killing dynamics of NK cells interacting with cancer cells. Full article

We report a novel approach to study cell migration under physical stresses by utilizing established growth factor chemotaxis. This was achieved by studying cell migration in response to epidermal growth factor (EGF) chemoattraction in a gradually tapered space, imposing mechanical stresses. The device consisted of two 5-mm-diameter chambers connected by ten 600 µm-long and 10 µm-high tapered microchannels. The taper region gradually changes the width of the channel. The channels tapered from 20 µm to 5 µm over a transition length of 50 µm at a distance of 250 µm from one of the chambers. The chemoattractant drove cell migration into the narrow confines of the tapered channels, while the mechanical gradient clearly altered the migration of cells. Cells traversing the channels from the wider to narrow-end and vice versa were observed using time-lapsed imaging. Our results indicated that the impact of physical stress on cell migration patterns may be cell type specific. Full article

In general, cell culture-based assays, investigations of cell number, viability, and metabolic activities during culture periods, are commonly performed to study the cellular responses under various culture conditions explored. Quantification of cell numbers can provide the information of cell proliferation. Cell viability study can understand the percentage of cell death under a specific tested substance. Monitoring of the metabolic activities is an important index for the study of cell physiology. Based on the development of microfluidic technology, microfluidic systems incorporated with impedance measurement technique, have been reported as a new analytical approach for cell culture-based assays. The aim of this article is to review recent developments on the impedance detection of cellular responses in micro/nano environment. These techniques provide an effective and efficient technique for cell culture-based assays. Full article