An on-chip deformability checker is proposed to improve the velocity–deformation correlation for red blood cell (RBC) evaluation. RBC deformability has been found related to human diseases, and can be evaluated based on RBC velocity through a microfluidic constriction as in conventional approaches. The correlation between transit velocity and amount of deformation provides statistical information of RBC deformability. However, such correlations are usually only moderate, or even weak, in practical evaluations due to limited range of RBC deformation. To solve this issue, we implemented three constrictions of different width in the proposed checker, so that three different deformation regions can be applied to RBCs. By considering cell responses from the three regions as a whole, we practically extend the range of cell deformation in the evaluation, and could resolve the issue about the limited range of RBC deformation. RBCs from five volunteer subjects were tested using the proposed checker. The results show that the correlation between cell deformation and transit velocity is significantly improved by the proposed deformability checker. The absolute values of the correlation coefficients are increased from an average of 0.54 to 0.92. The effects of cell size, shape and orientation to the evaluation are discussed according to the experimental results. The proposed checker is expected to be useful for RBC evaluation in medical practices.

Red blood cell responses during a long-standing load were experimentally investigated. With a high-speed camera and a high-speed actuator, we were able to manipulate cells staying inside a microfluidic constriction, and each cell was compressed due to the geometric constraints. During the load inside the constriction, the color of the cells was found to gradually darken, while the cell lengths became shorter and shorter. According to the analysis results of a 5 min load, the average increase of the cell darkness was 60.9 in 8-bit color resolution, and the average shrinkage of the cell length was 15% of the initial length. The same tendency was consistently observed from cell to cell. A correlation between the changes of the color and the length were established based on the experimental results. The changes are believed partially due to the viscoelastic properties of the cells that the cells’ configurations change with time for adapting to the confined space inside the constriction.

This paper proposes a microfluidic device which can perform simultaneous observation on cell growth with and without applying periodic hydrostatic pressure (Yokoyama et al. Sci. Rep. 2017, 7, 427). The device is called on-chip cell incubator. It is known that culture with periodic hydrostatic pressure benefits the elasticity of a cultured cell sheet based on the results in previous studies, but how the cells respond to such a stimulus during the culture is not yet clear. In this work, we focused on cell behavior under periodic hydrostatic pressure from the moment of cell seeding. The key advantage of the proposed device is that we can compare the results with and without periodic hydrostatic pressure while all other conditions were kept the same. According to the results, we found that cell sizes under periodic hydrostatic pressure increase faster than those under atmospheric pressure, and furthermore, a frequency-dependent fluctuation of cell size was found using Fourier analysis.

This paper reports the development of a micro-heater array device that can be selectively heated at an arbitrary location. To confirm the heating characteristics of this micro-heater array device, heating experiments using a thermo-responsive gel were conducted. Since a micro-heater can supply heat with a rapid-response on a micro-scale, various applications have been studied. Based on these characteristics, micro-heaters have often been used in recent research applications involving biological cells. To expand the versatility of the micro-heater, the development of micro-heater array systems that can supply heat selectively at an arbitrary location is required. In this work, to support micro-heater applications in the field of biochemistry, the design and materials of a micro-heater array device were optimized and a fabrication process was established. Furthermore, the usefulness of this device was verified using a thermo-responsive gel, and control of the temperature distribution on a glass substrate was successfully demonstrated. This micro-heater array device can be heated with regional selectivity, and each region can be controlled to an arbitrary temperature, so the device is also capable of generating temperature gradients.

In cell culture, the pH of the culture medium is one of the most important conditions. However, the culture medium may have non-uniform pH distribution due to activities of cells and changes in the environment. Although it is possible to measure the pH distribution with an existing pH meter using distributed electrodes, the method involves direct contact with the medium and would greatly increase the risk of contamination. Here in this paper, we propose a computed tomography (CT) scan for measuring pH distribution using the color change of phenol red with a light-emitting diode (LED) light source. Using the principle of CT scan, we can measure pH distribution without contacting culture medium, and thus, decrease the risk of contamination. We have developed the device with a LED, an array of photo receivers and a rotation mechanism. The system is firstly calibrated with different shapes of wooden objects that do not pass light, we succeeded in obtaining their 3D topographies. The system was also used for measuring a culture medium with two different pH values, it was possible to obtain a pH distribution that clearly shows the boundary.