Mechanical Processing of Biosamples

Tissue/Cell Spatial Dissection

Spatial dissection with blade array device
Blade array device


Optically-Driven Nanotools

Manipulation and processing using optically-driven nanotools
Nanotool fabrication with lithography process


  • M. Harada, H. Takao, F. Shimokawa, K. Terao*: “Development of optically driven nanoneedles using SU-8 nanofabrication”, Electronics and Communications in Japan, 105(1), e12327 (2022)
  • K. Terao*, C. Masuda, R. Inukai, M. Gel, H. Oana, M. Washizu, T. Suzuki, H. Takao, F. Shimokawa, F. Oohira: “Characterization of optically-driven microstructures for manipulating single DNA molecules under a fluorescence microscope”, IET Nanobiotechnology, 10(3), 124-128(2016)

Assembly of Organs from Single Cells

In the fields of drug discovery and regenerative medicine, it is expected that organ structures can be formed in vitro to replace animal experiments, or to be used in the preliminary stages for clinical trials as samples that are closer to in vivo conditions than normal cultured cells. Methods of self-assembling cell clusters and bioprinting have been proposed, but it is difficult to control the type and position of the cells at the single-cell level. To solve this problem, we aim to assemble individual cells as desired and form various cellular tissue structures.

Cell assembly
Cell cluster formation


  • S. Mori, T. Ito, H. Takao, F. Shimokawa, K. Terao*: “Optically-driven microtools with an antibody-immobilized surface for on-site cell assembly”, IET Nanobiotechnology, 1-7 (2023)

Single Molecule Mechanical Processing

Biomolecules are usually processed as a mass of molecules in aqueous solution. Therefore, information on individual molecules is lost and averaged. In addition, DNA molecules, a typical biomolecule, are linear polymers, but they are easily fragmented by the sheer flow of solution, making it difficult to treat the molecules intact. Therefore, most of the widely used biomolecular analysis techniques target molecular populations, and for DNA molecules, analysis is performed by amplifying the fragmented DNA molecules. In this process, differences between individual molecules, spatial structure and function are lost. Therefore, we are developing technologies to manipulate, process, and analyze molecules on a molecule-by-molecule manner, rather than on a collective.

Manipulation of single chromosomal DNA molecule
Single DNA molecule cutting


  • A. Masuda, H. Takao, F. Shimokawa, K. Terao*: “On-site processing of single chromosomal DNA molecules using optically driven microtools on a microfluidic workbench”, Scientific Reports, 11, 7961 1-9 (2021)
  • R. Inukai, H. Takao, F. Shimokawa, K. Terao*: “Capture and elongation of single chromosomal DNA molecules using optically-driven microchopsticks”, Biomicrofluidics, 14, 044114 (2020)
  • K. Terao*, M. Washizu, H. Oana: “On-Site Manipulation of Single Chromosomal DNA Molecules by using Optically Driven Microstructures”, Lab on a Chip, 8(8), 1280-4 (2008)

Single Cell Stimulation and Response Analysis

Local Drug Stimulation to Single Cell for Receptor Analysis

In drug discovery and cell biology, it is a fundamental experiment to measure the cellular response of cells to a drug. Many drugs target receptors exist on the cell surface. Receptors interact with drug molecules to induce or inhibit cellular responses. The relationship between the number of receptors that interact with a drug and the amount of cellular response is thought to be different for each cell type and cell state, but is not well understood. In this research, we are focusing on this point and developing a technology to analyze the relationship between drug-receptor interactions and cellular responses on single cell resolution using microfluidic devices. This technology will contribute to drug discovery and personalized medicine by clarifying the response of each cell.

Microfluidic device for local stimulation to single cells
Local glucose stimulation to single pancreatic beta cell


  • K. Terao*, M. Gel, A. Okonogi, A. Fuke, T. Okitsu, T. Tada, T. Suzuki, S. Nagamatsu, M. Washizu, H. Kotera: “Subcellular Glucose Exposure Biases the Spatial Distribution of Insulin Granules in Single Pancreatic Beta Cells”, Scientific Reports, 4, 4123 1-6 (2014)
  • K. Terao*, A. Okonogi, A. Fuke, T. Okitsu, T. Suzuki, M. Washizu, H. Kotera: “Localized substance delivery to single cell and 4D imaging of its uptake using a flow channel with a lateral aperture”, Microfluidics and Nanofluidics, 12(1), 423-429 (2012)

Drug Stimulation to iPS Embryoid Body for Differentiation Control

The process of transforming iPS cells into target cells is called differentiation induction. Differentiation induction is performed using drugs, etc., but cells that remain undifferentiated or are not the target cells are generated, resulting in a heterogeneous cell population even when the same differentiation induction procedure is performed. This heterogeneity in differentiation induction is one of the hurdles to the practical use of iPS cells from the viewpoint of the risk of tumor formation and cell quality assurance.

Microdevice for differentiation induction
Embryoid bodies of iPS cells


  • N.  Kusunoki, S. Konagaya, M. Nishida, S. Sato, H. Takao, F. Shimokawa, K. Terao*: “Microfluidic device for differentiation induction of iPS cells with local chemical stimulation”, Electronics and Communications in Japan, 105(3), e12393 (2023)

In Vitro Model for Analyzing Blood Circulation of Cancer Cells

Most cancer deaths are accompanied by metastasis, a process in which cancer cells circulate in the bloodstream. It is extremely difficult to observe this process in vivo due to the rarity and rapid move of cancer cells in the blood. Therefore, technologies have been proposed to reproduce the blood circulation process of cancer cells in vitro. In particular, considerable attention has been paid to the behavior of cancer cells in capillaries, which are thought to have a significant impact on metastasis, and how cancer cells deform and pass through constrictions and how they recover and change their properties once they pass through remain unsolved.

In vitro capillary constriction model
Cancer cell deformation and recovery


Biosample Manipulation

Microfluidic Device Reproducing Kidney Microenvironment

We are developing a microfluidic device to reproduce a kidney microenvironment in vitro. In particular, we aim to reproduce the conditions of septic acute kidney injury (AKI) to understand disease mechanisms and to develop effective therapies. However, it is difficult to observe them in vivo.

Microfluidic device reproducing AKI microenvironment
Culture and stimulation of tubular cells

“Molecular Ring Toss” for Imaging Single Circular DNAs

Conformational changes in DNA molecules play an important role in the maintenance of living functions and diseases through the expression and repression of functions in cells. For this reason, many methods have been developed to measure the dynamics of single DNA molecules. However, most of them are limited to DNA molecules on a linear strand with ends. In contrast, we focused on circular DNA molecules. Since circular DNA molecules do not have ends, they are suitable for observing specific conformational changes such as molecular twisting and relaxation

Molecular ring toss device
Imaging of circular DNA molecules


  • D. Dohi, K. Hirano*, K. Terao*: “Molecular ring toss of circular BAC DNA using micropillar array for single molecule studies”, Biomicrofluidics, 14, 014115 (2020)

2-Dimentional Micronozzle Array

A micro-nozzle that dispenses solution through a tiny aperture can be used to fabricate fine fibers and perform chemical processing on a limited area of a substrate surface. For this reason, they are used in bioprinting and biopatterning. If these micro-nozzles can be densely integrated in a two-dimensional array, it is expected that complex flows of various solutions can be formed from the apertures, leading to the in vitro formation of organs and highly integrated biosensors.

Stainless micro nozzle array
Formation of heterogeneous gel fiber


  • K. Takahashi, H. Takao, F. Shimokawa, K. Terao*: “On-demand formation of heterogeneous gel fibers using two-dimensional  micronozzle array”, Microfluidics and Nanofluidics, 26, 15 (2022)
  • K. Takahashi, S. Kamiya, H. Takao, F. Shimokawa, K. Terao*: “Stainless Microfluidic Probe with 2D array Microapertures”, AIP Advances, 11(1), 015331 (2021)

Previous Works

Surface Biosensing Enhanced by Microstructures

Blood testing with filter SPR sensor chip
Electric-field-assisted SPR sensing


  • K. Terao*, S. Kondo: “AC-Electroosmosis-Assisted Surface Plasmon Resonance Sensing for Enhancing Protein Signals with a Simple Kretschmann Configuration”, Sensors, 22(3), 854 1-9 (2022)
  • K. Terao*, S. Hiramatsu, T. Suzuki, H. Takao, F. Shimokawa, F. Oohira: “Fast protein detection from raw blood by size-exclusion SPR sensing”, Analytical Methods, 7, 6483-6488 (2015)
  • N. Nagase, K. Terao*, N. Miyanishi, N. Tamai, N. Uchiyama, T. Suzuki, H. Takao, F. Shimokawa, F. Oohira: “Signal Enhancement of Protein Binding by Electrodeposited Gold Nanostructures for Application in Kretschmann-Type SPR Sensor”, Analyst, 137(21), 5034-5040 (2012)
  • K. Terao*, K. Shimizu, N. Miyanishi, S. Shimamoto, T. Suzuki, H. Takao, F. Oohira: “Size-Exclusion SPR Sensor Chip: Application to Detection of Aggregation and Disaggregation of Biological Particles”, Analyst, 137(9), 2192-2198 (2012)

Single Cell Manipulation for Cell-Cell Interaction Studies

Heterotypic cell positioning
Non-contact cell positioning


  • Y. Tao, K. Fukuda, H. Takao, F. Shimokawa, and K. Terao*: “Development of microfluidic device for imaging paracrine communication”, IEEJ Transactions on Sensors and Micromachines, 137(5), 128-133(2017)
  • K. Terao*, Y. Kitazawa, R. Yokokawa, A. Okonogi, H. Kotera: “Open-Access and Multi-Directional Electroosmotic Flow Chip for Positioning Heterotypic Cells”, Lab on a Chip, 11(8), 1507-1512(2011)