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Robot-integrated microfluidic chip is a promising tool to realize mechanical characterization of a single cell with high throughput and high accuracy. The microfluidic chip used in our system has a pair of mechanical microprobes to measure deformation and reaction force of cells. In our previous studies, we measured the elasticity of cells in this measurement system. However, there were some problems...
This paper reports an ultra-fast manipulation on micro-scale objects in a microfluidic channel. The objects are manipulated in simple harmonic motions and the manipulation speed has been achieved up to 3000 Hz. While the maximum speed was only about 130 Hz in previous works, the speed is advanced with an additional order in this work. Based on the experimental results, we find that the gain decreases...
This paper discusses an on-chip Red Blood Cell (RBC) deformability checker with vision analyzer. The system is composed of a PDMS chip including three microfluidic channels, a microscope for appropriately enlarging RBC, and a high-speed vision for observing both the cell size and behaviors in the channel, respectively. We particularly focus on how to analyze the deformability of single cells by the...
This paper proposes a hybrid actuation for long-term cell manipulation in a microfluidic channel. While a conventional actuation can manipulate a cell, it usually cannot last for a very long time (i.e. less than 10 minutes) due to unavoidable pressure leak or drifts. The hybrid actuation is composed of two actuations where one is a gravity-based pressure system for macro-scale pressure balancing and...
An interesting phenomenon of microfluidic vortices rotating and transmitting like a set of gears has been experimentally observed and is named "Virtual Vortex Gear". We found that the vortices could be serially induced by increasing the driving pressure. Every two closed by vortices were having opposite directions of the swirling. The relation between the vortices and driving pressure has...
We report a simple and effective method for adjusting the gain of cell manipulation in a microfluidic channel. The gain of the manipulation is defined as the ratio of the displacements between the actuator and a target cell. The gain is found adjustable by controlling the offset pressure in the channel. According to the experimental results, the gain is about proportional to the offset pressure within...
A novel microfluidic system for applying cyclic pressure to cells during incubation is developed and tested in this work. The cyclic pressure generates stress stimulus to the cells, and is named “Cell Exercise” in this work. The goal of this paper is to design an “On-Chip Cell Gym” where we can observe what happens during the cell exercise in real-time. We design the cell gym on a PDMS chip composed...
This paper focuses on the comparison of red blood cell (RBC) deformability under continuous and repetitive loadings. We utilized a feedback position-control system and a narrow microfluidic channel for applying different deformation patterns on RBCs. According to the analyses of shape recoveries with different patterns, we found, for the first time, that the mechanical responses of RBCs upon continuous...
“Cell Pinball” is a phenomenon whereby rotating red blood cells (RBCs) move like pinballs inside a microfluidic channel where the cell inertia is negligible. The goal of this paper is to discuss the location of the actual rotational axis through the careful comparison between the contour and contact shapes of a moving RBC. By switching the reflection interference contrast (RIC) and the phase contrast...
Different cell buckling between positive and negative driving pressure in a microfluidic channel is investigated. Red blood cells under three different osmotic conditions have significant differences between positive and negative driving pressures. Cell insertion length is employed as an index for cell buckling. Greater variations of the insertion length are found with negative driving pressure. This...
Many researches have reported that the mechanical stimulus is important factor of the histogenesis and cellular differentiation. However, it is not clearly understood for cellular nucleus how to respond to the mechanical stimulus. Our purpose is applying a mechanical stimulus to cells for gene expression assay. On this paper, we report development of a micro-channel device and evaluating the device...
We propose a method to measure cellular elasticity using large compression model. Unlike Hertzian contact theory, this model can be fit to the experimental data even in large deformation area. This model is suitable for on-chip system to measure elasticity of cell using indentation of flat probes.
In this paper, we focus on mechanical characterization of human umbilical vein endothelial cell(HUVEC) and mesenchymal stem cell(MSC) co-cultured spheroids. HUVEC/MSC co-cultured spheroid has a characteristic that the size becomes compact with culture day increase. In order to measure the mechanical characteristics of size changing spheroids, we apply whole chip deformation mechanism to the actuation...
A surprising phenomenon is observed in a microfluidic channel where suspending microbeads are spontaneously aligned into lines. Microbeads are randomly distributed in the channel at a relatively high velocity (3.27 µm/ms), but start to align into lines at a relatively low velocity (0.05 µm/ms). The alignment has been repeated with and without obstacles in the channel. The phenomenon is interpreted...
A high-resolution cell manipulation system is presented for investigating red blood cell deformation under long-standing load in this paper. Because the low Reynolds number in microfluidic system, cell position can be manipulated by controlling the flow in a microchannel. A high-speed vision system is embedded in the system for providing cell present position as the feedback signal for the controller...
An automatic system for evaluating single cell viscoelasticity is proposed and tested in this paper. The system includes three main operations, and they are the operations of catch, load and launch. In the catch operation, the system is capable of capturing a target cell by high-speed vision and high-frequency flow control. The captured cell is pushed into a narrow constriction for the load operation...
We present a method which can evaluate stiffness of cell-spheroids, and show the measurement results of the stiffness changes with respect to the culture time. To obtain the stiffness-index map, where the map shows the relationship between the size and stiffness of cell-spheroids, we applied on-chip measurement method using a robot integrated microfluidic chip (robochip). The robochip has a microchannel...
We propose a method to measure displacement of microscale structures with high sensing resolution and large stroke on focal plane of microscopy. Using this method, measurable displacement become approximately 10 times larger than that of the conventional method, and the resolution is kept as small as tens nm order.
The frequency responses of a previously proposed on-chip pressure sensor is investigated with two different sizes of deformation chamber. Pressure inputs with the same span of frequencies, from 1 Hz to 64 Hz, are applied to the fabricated pressure sensors, and the pressure sensed by the on-chip sensor is represented by the movement of microbeads inside the sensing area. We found that the sensor with...
We present a method of cell mechanical characterization using a robot integrated microfluidic chip (robochip). The robochip has a microchannel, a force sensor and an on-chip probe. On-chip probe is actuated by whole chip deformation mechanism. Firstly, we designed the robochip. Secondary, we fabricated the robochip. Finally, we measured the young's modulus of zona pellucida by using Hertz contact...
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