Hirotaka Sugiura

On-Chip Method to Measure Mechanical Characteristics of a Single Cell by Using Moiré Fringe

We propose a method to characterize the mechanical properties of cells using a robot-integrated microfluidic chip (robochip) and microscopy. The microfluidic chip is designed to apply the specified deformations to a single detached cell using an on-chip actuator probe. The reaction force is simultaneously measured using an on-chip force sensor composed of a hollow folded beam and probe structure. In order to measure the cellular characteristics in further detail, a sub-pixel level of resolution of probe position is required. Therefore, we utilize the phase detection of moire fringe. Using this method, the experimental resolution of the probe position reaches 42 nm. This is approximately ten times smaller than the optical wavelength, which is the limit of sharp imaging with a microscope. Calibration of the force sensor is also important in accurately measuring cellular reaction forces. We calibrated the spring constant from the frequency response, by the proposed sensing method of the probe position. As a representative of mechanical characteristics, we measured the elastic modulus of Madin-Darby Cannie Kidney (MDCK) cells. In spite of the rigid spring constant, the resolution and sensitivity were twice that achieved in our previous study. Unique cellular characteristics can be elucidated by the improvements in sensing resolution and accuracy.

Large Indentation Method to Measure Elasticity of Cell in Robot-Integrated Microfluidic Chip

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 on the measurement method limited in small deformation regions of cell. To avoid these problems, we changed the measurement method to utilize large deformation regions of cell. First, we proposed a differential-type sampling moiré method to extend the range of the force or displacement measurement. Second, the mechanical model of the cell was improved to express the deformation characteristics up to large deformation region. The deformation model was derived from high-molecular theory. Therefore, the measured elasticity was related to the intracellular filament network. As a result, we accomplished in measuring the elasticity of the cells using the experimental data in a large deformation region. This study provided us with a more practical and reliable method to measure cellular elasticity.

On-chip measurement of cellular mechanical properties using moiré fringe

This paper proposes the method for mechanical characterization of floating cells on a microfluidic chip. We measured the reactive force of cells on the chip by applying mechanical deformation to the cells. Particularly we focused on the method to improve the sensing resolution of the probe position by using the phase detection of moiré fringe. This method realized approximately ten times higher resolution compared to the previous method. The detailed data suggest some unique characteristics of cells. We discussed the phenomenon seen on the data with a mechanical model, which is based on Heltzian contact theory in the light of stiff nucleus.

Elasticity evaluation of single cell with uniaxial deformation in microfluidic chip

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.

On-chip Method to Measure Elastic Property of Single Cell Using Large Compressive Deformation Model

This paper proposes a method to measure cellular elasticity on a microfluidic chip using large compressive deformation model. In our previous researches, we succeeded in improving accuracy and sensitivity of measurement devices using piezoelectric actuator and sampling moire method. However, there still were some problems on the analysis of mechanical properties of cell. Conventional studies employed Hertzian Contact Theory, which could be utilized in quite limited area of cell compression. Therefore, this theory could not be adaptive to on-chip measurement system based on uniaxial large compression mechanism. In this research, we introduce a large compressive deformation model to illustrate elastic behavior of single cell in detail. This is naturally extended model of Hertzian Contact Theory, and in good accordance with the experimental data. Using iterative least square estimation method, we succeed in demonstrating elasticity measurement based on the new model.

A method to measure displacement of microscale structures with high resolution and large stroke for cellular characterization

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.

Measurement of cellular reactive force on a microfluidic chip using moiré fringe

In this paper we propose the method for the measurement of cellular mechanical response on a microfluidic chip. In order to improve the sensing resolution, we applied the principle of moiré fringe. As a result, the resolution of the measurement is approximately ten times higher than our previous research.