Laboratory for Future Interdisciplinary Research of Science and Technology, Institute of Integrated Research, Institute of Science Tokyo Nisisako Group Microfluidic Interface Lab.

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Research Topics

Below are some examples of the research topics in our lab.

3D-Printed Droplet Separation Device NEW

3D-Printed Droplet Separation Device

We developed a low-cost, 3D-printed microfluidic device that integrates droplet generation and deterministic lateral displacement (DLD) for continuous separation of main and satellite droplets. Using a desktop SLA 3D printer, deep microchannels and post arrays were fabricated to process large droplets (>200 µm), which are difficult to handle with conventional lithography. The device enables robust size-based separation and subsequent synthesis of monodisperse polymer particles, demonstrating the potential of accessible 3D printing for scalable droplet and particle microfluidics.

Selected Papers

  1. Tang et al., Ind. Eng. Chem. Res. 65, 873–881 (2026)

Biosensing of Nucleic Acid Therapeutics NEW

Biosensing of Nucleic Acid Therapeutics

We proposed an electrochemical sensing approach for charge-neutral antisense oligonucleotides (ASOs) using Viltolarsen as a model target. Hairpin DNA (or RNA) probes immobilized on nanostructured gold electrodes enabled electrochemical monitoring of hybridization. Although the signal change was smaller than that for negatively charged DNA targets, the response was faster and formed a stable duplex. These behaviors originate from reduced electrostatic repulsion, providing design guidelines for ASO-targeted biosensors.

Selected Papers

  1. Kanno et al., ACS Electrochem. , 2026, DOI:10.1021/acselectrochem.5c00384

Thermally Tunable Cell-Sorting Device NEW

Thermally Tunable Cell Separation Device

We have developed a microfluidic device capable of temperature-controlled cell separation. By integrating thermo-responsive hydrogel micropillars into a hybrid microchannel, the device enables dynamic tuning of the critical diameter (Dc), allowing flexible separation of target cells, such as cancer cells, from complex samples. This platform achieves high-purity, label-free sorting while preserving cell viability. The innovation offers promising applications in medical diagnostics, rare cell isolation, and future cell-based therapies.

Selected Papers

  1. Science Tokyo Press Release: A new tunable cell-sorting device with potential biomedical applications (Dec. 3, 2025).Link
  2. Jiang et al., Lab Chip 25, 6454–6464(2025).
  3. Tottori et al., Sci. Rep. 13, 4994(2023).

Droplet Measurement by On-Chip Laser Diffraction NEW

Droplet Measurement by On-Chip Laser Diffraction

We developed an on-chip laser diffraction (LD) system integrated into a commercial inverted microscope for high-precision in-situ characterization of microfluidic droplets. In a PDMS cross-junction device, generated 20–50 µm O/W and W/O droplets were irradiated with a laser, and diffraction patterns were analyzed to obtain diameter and refractive index simultaneously. The system achieved detection limits of 0.1 µm in diameter and 0.004 in refractive index, with errors below 5% and 0.5%, respectively.

Selected Papers

  1. Masui et al., ACS Meas. Sci. Au 5, 647–655(2025).

Dual Production of Biconvex Particles from Ternary Droplets

Dual Production of Biconvex Particles from Ternary Droplets

This study presents a microfluidic method to generate surfactant-laden ternary droplets, enabling the simultaneous fabrication of two biconvex polymeric particles from a single droplet. Using two photocurable monomer streams and a silicone oil separator, nanoliter-sized ternary droplets are formed and photopolymerized off-chip. The approach doubles production yield compared to Janus droplets and allows precise control of particle size and shape by adjusting flow-rate ratios, offering a versatile and efficient route for producing tailored micro-optical elements and functional materials.

Selected Papers

  1. Xu et al., Sci. Rep. 15, 22936(2025).

Producing O/W Droplets Below 20 µm Using a PDMS Step Emulsification Device

Production of Monodisperse O/W Droplets Below 20 µm Using a PDMS Step Emulsification Device

We developed a PDMS step emulsification device with 264 triangular nozzles (height 4 µm, minimum width 10 µm, opening width 38 µm) rendered hydrophilic by oxygen plasma treatment. The device stably produced O/W droplets with mean diameters below 20 µm and CVs under 4%, achieving a maximum throughput of 0.5 mL h⁻¹. Off-chip photopolymerization yielded monodisperse acrylic microspheres of similar size.

Selected Papers

  1. Tottori et al., Micromachines 16, 132(2025).

Step Emulsification and DLD Separation

Step Emulsification and DLD Separation

Step emulsification generates monodisperse droplets using interfacial tension gradients and is resistant to flow rate variations, making it suitable for scale-up. However, satellite droplets are often by-products. This study developed a device with a DLD micropillar array downstream of the nozzle array to separate main droplets from satellite droplets. Using a scaled-up device with up to 1000 nozzles and DLD channels, 100% satellite-free monodisperse droplets were achieved.

Selected Papers

  1. Ji et al., Micromachines 15, 908(2024).
  2. Ji et al., Micromachines 14, 622(2023).

A Step Emulsification Device with a Slit Channel

A Step Emulsification Device with a Slit Channel

We have developed a new step emulsification device featuring parallel channels that intersect a slit channel perpendicularly. This device effectively guides the generated droplets from the vicinity of the nozzles along the slit channel to the outlet using the continuous phase flow, thereby preventing droplet retention near the nozzles and coalescence of droplets. As a result, monodisperse water-in-oil (W/O) or oil-in-water (O/W) droplets can be rapidly collected outside the device.

Selected Papers

  1. Zheng et al., Ind. Eng. Chem. Res. 64, 13720–13729(2025).
  2. Zheng et al., Ind. Eng. Chem. Res. 63, 10226–10233(2024).

Understanding Droplet Breakup in a Micropost Array

Understanding Droplet Breakup in a Micropost Array

Recent studies have highlighted the capability of generating relatively uniform (quasi-monodisperse) droplets by directing the flow of two immiscible liquids (e.g., water and oil) through an array of aligned microscopic posts. Our research has unveiled two distinct breakup modes contingent upon the shear force magnitude. Furthermore, it has been elucidated that the diameter of the resulting droplets exhibits a power-law correlation with Capillary number.

Selected Papers

  1. Masui et al., Lab Chip 23, 4959–4966(2023).

Particle Separation

Microfluidic Particle Separation

Particle separation is a crucial necessity across diverse fields, including analytical chemistry and material production. Our research group is studying a microfluidic technology that allows for highly efficient separation of particles through periodically arrayed microposts. Our accomplishments include the successful separation of polymer particles, droplets, cells, and more.

Selected Papers

  1. Tottori et al., RSC Adv. 7, 35516 (2017).
  2. Tottori et al., Biomicrofluidics 10, 014125 (2016).

Microlenses Fabrication

マイクロレンズ成型

We are pioneering a novel approach to fabricating microlenses, bypassing the need for a solid mold through droplet microfluidics. This technique involves the creation of multiphase droplets wherein a curable and non-curing liquids undergo phase separation. By subsequent photopolymerization, microlenses exhibiting diverse shapses (biconvex, biconcave, concave and convex) can be produced.

Selected Papers

  1. Nisisako et al., Micromachines 6, 1435–1444 (2015).
  2. Nisisako et al., Small 10, 5116–5125 (2014).
  3. Nisisako et al., 精密工学会誌 79, 460–466 (2013)

Artificial Lipid Bilayer Platform

人工脂質二分子膜

Lipid bilayer membranes serve as fundamental components in cell membranes. In recent years, systems utilizing artificial lipid bilayer membranes have found extensive applications in diverse areas such as electrophiological tests, biosensors, and artificial cell studies. We have developed a highly efficient method for fabricating planar lipid bilayers within microchannles or microchambers, facilitating rapid measurements of the in-vitro passsive membrane permeability of potential drug candidates.

Selected Papers

  1. Nisisako et al., Analyst 138, 6793-6800 (2013).

Parallelization for Scaled-Up Production

マイクロ流路の並列化による生産スケールアップ

We are conducting research on technology to scale up the production of various droplets and particles by parallelizing (numbering up) a large number of microchannels at high density. To date, we have parallelized tens to hundreds of microchannels on a chip of several centimeters square to increase the production rate of single-phase emulsion droplets, Janus droplets, multi-phase emulsions, and various fine particles with excellent size uniformity. We are conducting research aimed at further scaling up.

Selected Papers

  1. Nisisako et al., Lab Chip 12, 3426–3435 (2012).
  2. Nisisako et al., Lab Chip 8, 287–293 (2008).
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