Research

In medicine and biology, a number of technologies have been developed to analyze the types and amounts of biomolecules contained in single cells. On the other hand, spatial information on the location of the analyzed cells in the body and the organ from which they originated is often lost.
We are working on the development of a technology to sample cell-sized fractions with spatial information, that is, with the tag of where they originated from in an organ. This technology will make it possible to link the material information of analyzed cells with spatial information in organs, and is expected to lead to the analysis of cancer microstructures and the elucidation of the relationship between cytoarchitecture and function.

At the focus of a laser beam, tiny objects with sizes ranging from nanometers to micrometers can be captured, which is known as optical tweezers. Our goal is to create various shapes of micro objects captured by optical tweezers and to apply surface treatment to them in order to harness the functions and use them as tools in the nano-world. By using such optically-driven nano/microtools, we are approaching areas that are difficult to handle in conventional bio experiments, such as manipulation and processing of a single cell and a single biomolecule.

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.

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.

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.

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.

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.

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.

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

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.