Photopatternable Hydrogel for Next-Generation Biomedical and Tissue Engineering Applications
2026
Kavitha Govarthanan, Lakshmi Krishnan, Akanksha Jha, Abinaya Rajendran, Moeto Nagai, Suresh Rao, Tuhin Santra
掲載先 / Source: Biomicrofluidics
発行者 / Publisher: AIP Publishing
Type: scientific_journal
査読あり / Peer reviewed国際誌 / International journal国際共著 / International collaborationMulti-parallel PDMS Nozzles for Biomaterial Droplet Arrays (Rapid Prototyping with VPP 3D-printed Molds)
2026-10
Rifat Hussain Chowdhury, Muhammad Awais Maqbool, Shunya Okamoto, Takayuki Shibata, Tuhin Subhra Santra, Moeto Nagai
掲載先 / Source: Mechanical Engineering Journal
発行者 / Publisher: The Japan Society of Mechanical Engineers
Type: scientific_journal
査読あり / Peer reviewed国際共著 / International collaborationLLM-driven rapid prototyping of microfluidic devices: a deterministic Python-mediated framework for design, fabrication, and validation
2026-09-23
Muhammad Aneeq, Nazim Khatana, Muhammad Aqib Raza Shah, Takayuki Shibata, Shunya Okamoto, Tuhin Subhra Santra, Moeto Nagai
掲載先 / Source: Rapid Prototyping Journal
発行者 / Publisher: Emerald
Type: scientific_journal
Pages: 1–13
査読あり / Peer reviewed国際誌 / International journal国際共著 / International collaboration説明・概要 / Description
Purpose
Microfluidic device design remains time-intensive and heavily reliant on computer-aided design (CAD) expertise, which limits scalability in rapid prototyping, high-throughput experimentation and standardized design workflows. While large language models (LLMs) offer a route toward automated CAD, existing script-based CAD tools, e.g. CADQuery, are prompt-sensitive and prone to geometric inconsistencies. This study aims to enable reliable rapid prototyping by accelerating the design-to-fabrication cycle through an LLM-assisted, Python-mediated framework for microfluidics and performing physical fabrication and dimensional validation to confirm whether designs meet manufacturing tolerances and functional requirements.
Design/methodology/approach
ChatGPT is used to generate a closed-loop Python script, executed through a Python script that generates scalable vector graphics (SVG), drawing exchange format (DXF) and standard tessellation language (STL) outputs of microfluidic geometries, including Spiral Mixers, T-Junctions and Y-Junctions along with script execution time. Each design run is logged with a cryptographic hash to ensure traceability and confirm reproducibility. Physical fabrication using fused deposition modelling and dimensional validation using optical metrology on a digital microscope were essential to confirm whether designs meet manufacturing tolerances and functional requirements. Device functionality was assessed through pressure resistance evaluation, with indicative pressure-drop estimates calculated at leakage onset using the Hagen–Poiseuille approximation.
Findings
ChatGPT/Python workflow substantially reduces iteration time compared with the manual CAD workflow. Post-fabrication measurements showed dimensional deviations up to 12.6% across all geometries while iterative compensation further reduced dimensional deviations. Pressure resistance testing confirmed indicative functional device integrity within low-to-moderate flow regimes, with leakage onset observed at flow rates consistent with fused deposition modelling-related sealing limitations, with no evidence of gross geometric errors in the generated CAD files.
Originality/value
This workflow separates probabilistic LLM interaction from deterministic geometry execution. It provides a traceable route from design generation to exploratory fabrication, supported by cryptographic logging, dimensional validation and iterative compensation.
Light-activated, highly efficient intracellular biomolecular delivery using a titanium nitride micro-array device
2026-07
Nandhini Balasubramaniam, Srabani Kar, Amal Kanti Bera, Moeto Nagai, Tuhin Subhra Santra
掲載先 / Source: The Analyst
発行者 / Publisher: Royal Society of Chemistry (RSC)
Type: scientific_journal
査読あり / Peer reviewed国際誌 / International journal国際共著 / International collaboration説明・概要 / Description
A titanium nitride micro-array device for light-activated cell therapy uses near-infrared pulsed laser irradiation to induce transient membrane pores, thereby enabling the intracellular delivery of biomolecules.
Phototaxis and Motility of Euglena gracilis in Physiological Saline via Stepwise Acclimation for Biohybrid Microrobotics
2026-07-06
Kaiya Endo, Soshi Morimoto, Hayato Obayashi, Takayuki Shibata, Shunya Okamoto, Tuhin Subhra Santra, Moeto Nagai
掲載先 / Source: Micromachines
発行者 / Publisher: MDPI AG
Vol.: 17
No.: 7
Type: scientific_journal
Pages: 815–815
査読あり / Peer reviewed国際誌 / International journal国際共著 / International collaboration説明・概要 / Description
Microrobots navigating the human body require biocompatible actuators capable of functioning in physiological fluids. The microalga Euglena gracilis offers precise phototactic control; however, its operational stability in simulated physiological environments remains unproven. Here, we report that a stepwise acclimation process preserves the robotic functionality of E. gracilis in 100% phosphate-buffered saline (PBS), 100% fetal bovine serum (FBS), and a NaCl solution at a concentration equivalent to PBS (137 mM). We compared direct transfer against a graduated adaptation protocol, evaluating morphology, swimming speed, motility rate, and phototaxis. Direct transfer to each medium caused near-total immobilization, whereas stepwise acclimation retained motility. Acclimated cells exhibited size reduction (miniaturization) while maintaining their characteristic eccentricity. These adapted cells sustained a negative phototactic response among the remaining motile population, supporting optical controllability despite reduced swimming speed. These results indicate that stepwise acclimation allows E. gracilis to retain partial motility and phototactic controllability under simulated physiological saline conditions, and that the observed miniaturization and preserved photo-responsiveness may be useful features for future biohybrid microrobotics.
A biomimetic microfluidic triple-compartment periodontium-on-chip model for investigation of inflammatory responses in periodontitis
2026-06
Abinaya R., Kavitha Govarthanan, Lakshmi Krishnan, Ki-Taek Lim, Moeto Nagai, Suresh Rao, Tuhin Subhra Santra
掲載先 / Source: Small
発行者 / Publisher: Wiley
Type: scientific_journal
査読あり / Peer reviewed国際誌 / International journal国際共著 / International collaboration量子技術教育導入を見越したデジタルマイクロミラーデバイスを用いた光波制御システムの構築
2026-06
野田陽太, 永井萌土, 河野託也
掲載先 / Source: 応用物理教育
発行者 / Publisher: 公益社団法人応用物理学会応用物理教育分科会
Vol.: 50
No.: 1
Type: scientific_journal
査読あり / Peer reviewedFully Automated Multi-Sample Sandwich ELISA Device with Flow-Measurement-based Mold Optimization for Practical Applications
2026-05
Yusuke Kanai, Moeto Nagai, Takayuki Shibata, Yoshiaki Ukita, Shunya Okamoto
掲載先 / Source: Sensors and Actuators B: Chemical
発行者 / Publisher: Elsevier BV
Type: scientific_journal
Pages: 140146–140146
査読あり / Peer reviewed国際誌 / International journalForce-Sensor-Integrated Soft Microfinger for Mechanical Stimulation and Reaction Generated Force Evaluation of Zebrafish Larvae
2026-05
Tomohiro Nakatsuka, Hiromi Hirata, Moeto Nagai, Satoshi Konishi
掲載先 / Source: Scientific Reports
発行者 / Publisher: Springer Nature
Type: scientific_journal
査読あり / Peer reviewed招待 / Invited国際誌 / International journalBeyond the Black Box: Resin Viscosity and Tensile Strength as Fabrication Guides for VPP 3D-Printed Microfluidic Molds
2026-04-24
Rifat Hussain Chowdhury, Shunya Okamoto, Takayuki Shibata, Tuhin Subhra Santra, Moeto Nagai
掲載先 / Source: Micro
Vol.: 6
No.: 2
Type: scientific_journal
査読あり / Peer reviewed国際誌 / International journal国際共著 / International collaborationReduced Bubbles in a PDMS SlipChip: Magnetic Alignment, Oil-Infused Lubrication, and Geometry Optimization
2026-03-21
Rafia Inaam, Imran M., Hussain Mohammad, Hirofumi Yamamoto, Marcela F. Bolontrade, Shunya Okamoto, Takayuki Shibata, Tuhin Subhra Santra, Moeto Nagai
掲載先 / Source: Applied Sciences
発行者 / Publisher: MDPI AG
Vol.: 16
No.: 6
Type: scientific_journal
Pages: 3040–3040
査読あり / Peer reviewed国際誌 / International journal国際共著 / International collaboration説明・概要 / Description
PDMS SlipChips are vital for precision medicine, but their performance often degrades when solutions leak or air pockets become trapped between layers. These failures stem from the inherent stickiness of PDMS and uneven surface contact, as the sliding nature of the device prevents permanent sealing. This work addresses these technical hurdles by integrating magnetic clamping with oil-infused lubrication and refined microwell geometries. A 3D-printed magnetic fixture maintains steady contact pressure during operation, while custom-made microstages provide the precise control needed to align microwells across the x–y plane. By allowing the porous PDMS to absorb silicone oil, we created a stable lubricating interface that prevents leakage and reduces friction without sacrificing mobility. We found that a microwell-to-channel width ratio of five substantially suppresses bubble formation compared with narrower designs. These enhancements ensure the generation of consistent, discrete concentration gradients and establish a reliable platform for high-throughput assays using minute sample volumes.
Advanced Photoporation: Micro‐Nanostructures for Size‐Specific Highly Efficient Biomolecular Delivery
2026-02-07
Ashwini Surendra Shinde, Gayathri R., Nandhini Balasubramaniam, Athira Prasad, Donia Dominic, Moeto Nagai, Srabani Kar, Tuhin Subhra Santra
掲載先 / Source: Small
発行者 / Publisher: Wiley
Vol.: 22
No.: 16
Type: scientific_journal
査読あり / Peer reviewed国際誌 / International journal国際共著 / International collaboration説明・概要 / Description
ABSTRACT
With the growing demand for precise and minimally invasive intracellular delivery, photoporation has emerged as a powerful non‐viral strategy. This review presents a comprehensive analysis of photoporation as a versatile intracellular delivery platform, with particular emphasis on the role of micro‐ and nanostructured materials in enabling efficient transport across a wide range of biomolecular sizes. A key novelty of this review is its size‐centric organizational framework, which systematically classifies photoporation strategies based on biomolecular cargo size, from small molecules and nucleic acids to ultralarge assemblies and bacteria, rather than conventional material‐ or laser‐based categorizations. The review examines laser‐induced mechanisms responsible for transient membrane permeabilization and highlights critical material parameters, including composition, size, shape, surface charge, and optical properties, that govern light–matter interactions and delivery efficiency. Comparative evaluation of micro‐ and nanostructured materials across different size regimes provides a practical framework for rational material selection and platform design. In addition, key challenges related to delivery precision, biocompatibility, scalability, and clinical translation are critically discussed alongside emerging optimization strategies. By integrating mechanistic insights with translational considerations, this review provides a structured roadmap for developing safe, efficient, and size‐adaptive photoporation platforms for biological research and therapeutic applications.
Titanium Nitride Nanomaterials—A New Horizon for Light‐activated human Mesenchymal Stem Cell and Cancer Cell Therapy
2026-02-04
Nandhini Balasubramaniam, Ranjith Balakrishnan, Amal Kanti Bera, Moeto Nagai, Rajasekaran Subbarayan, Srabani Kar, Tuhin Subhra Santra
掲載先 / Source: Advanced Therapeutics
発行者 / Publisher: Wiley
Vol.: 9
No.: 2
Type: scientific_journal
査読あり / Peer reviewed国際誌 / International journal国際共著 / International collaboration説明・概要 / Description
ABSTRACT
Optoporation enables high‐precision delivery of biomolecules for treating diseases through cell therapy, gene editing, and personalized therapeutics. Nanoparticle‐based optoporation offers high transfection efficiency by minimizing cell damage, thus enhancing the overall cellular health. This study demonstrates the versatility of using Titanium nitride nanoparticles (TiN NPs)‐mediated optoporation for the delivery of small to large cargos, achieving high transfection efficiency alongside cell viability. TiN NPs adsorbed on the cell membrane, when irradiated with a laser fluence of 12.8 mJ/cm <sup>2</sup> at an 850 nm wavelength, generate plasmonic bubbles, facilitating the delivery of cargo into the cells. By using this platform, wide range of cargos/biomolecules such as propidium iodide (PI) dye (668.4 Da), dextran (3 kDa), small interfering RNA (siRNA) (13.3 kDa), enhanced green fluorescence protein (EGFP) expression plasmid DNA (229.4 kDa), and β‐ galactosidase enzyme (465 kDa) are delivered into diverse mammalian cell lines (L929, MG‐63, and N2a) with high transfection efficiency and cell viability. The functionality of the transfected β‐galactosidase enzyme is assessed by measuring its enzymatic activity, verifying the effectiveness of the transfection process. For small PI molecules, MG‐63 cells demonstrated a delivery efficiency of 98% with a cell viability of 99%. In contrast, for oversized cargo (enzyme, 465 kDa), the transfection efficiency and cell viability achieved were 97% and 99%, respectively. Furthermore, human mesenchymal stem cells (hMSCs) are transfected with the EGFP plasmid and β‐galactosidase enzyme, demonstrating a transfection efficiency of 98% and cell viability of 99%. To study the cytotoxicity of TiN NPs, an MTT assay, Kaplan‐Meier survival analysis, and behavioral assessment of the in vivo zebrafish model are conducted. The plots suggest that TiN NPs do not pose neurotoxic effects. Thus, this platform has demonstrated inherent potential for cell reprogramming and applications in medicine, molecular biology, and cellular biology.
Immobilized, micro-patterned graphene nanoflake devices for high-throughput, uniform intracellular biomolecular delivery
2026-01
Donia Dominic, Rajdeep Ojha, Moeto Nagai, Srabani Kar, Tuhin Subhra Santra
掲載先 / Source: Materials Advances
発行者 / Publisher: Royal Society of Chemistry (RSC)
Vol.: 7
No.: 4
Type: scientific_journal
Pages: 2279–2299
査読あり / Peer reviewed国際誌 / International journal国際共著 / International collaboration説明・概要 / Description
Micro-patterned rGO devices enable high-throughput intracellular biomolecular delivery.
Transparent SU-8 Micronozzle Array with Minimal Dead Volume for Parallel Liquid-to-Liquid Sample Ejection
2025-09
Kentaro Tanagi, Anuj Tiwari, Sho Kawaharada, Shunya Okamoto, Takayuki Shibata, Tuhin Subhra Santra, Moeto Nagai
掲載先 / Source: Micro
発行者 / Publisher: MDPI
Vol.: 5
No.: 3
Type: scientific_journal
査読あり / Peer reviewed国際誌 / International journal国際共著 / International collaborationA high-speed sequential liquid compartmentalization method for digital loop-mediated isothermal amplification in a microfluidic device
2025-08
Riku Honda, Taketo Saruwatari, Daigo Natsuhara, Yuka Kiba, Shunya Okamoto, Moeto Nagai, Masashi Kitamura, Takayuki Shibata
掲載先 / Source: Lab on a Chip
Vol.: 25
Type: scientific_journal
Pages: 4787–4799
査読あり / Peer reviewed国際誌 / International journalMassively parallel photosensitive hydrogel encapsulated single-cell to a cluster of cells patterning and bone regeneration application
2025-08
Sarin Abraham, Gayathri R., Kavitha Govarthanan, Suresh Ranga Rao, Moeto Nagai, Tuhin Subhra Santra
掲載先 / Source: Lab on a Chip
発行者 / Publisher: Royal Society of Chemistry
Vol.: 25
Type: scientific_journal
Pages: 4735–4755
査読あり / Peer reviewed国際誌 / International journal国際共著 / International collaborationHigh Throughput Intracellular Delivery Using a 2D Cell‐Squeezing Mechanoporation Device and Its Analysis by a Deep Learning Model
2025-08-21
Pulasta Chakrabarty, Abinaya R., Ryoma Suzuki, Srikanth Vedantam, Suresh Rao, Moeto Nagai, Tuhin Subhra Santra
掲載先 / Source: Advanced Healthcare Materials
発行者 / Publisher: Wiley
Vol.: 14
No.: 32
Type: scientific_journal
査読あり / Peer reviewed国際誌 / International journal説明・概要 / Description
Abstract
Cell‐squeezing mechanoporation is a simple method for intracellular delivery. Most studies rely on 1D constrictions; however, the throughput is limited. To enable parallel single‐cell delivery with higher throughput, a 2D cell‐squeezing microfluidic device is designed and fabricated. An array of vertical through‐holes, 8 to 15‐µm in diameter (up to 62 000 holes per device), is fabricated on a 20‐µm thin SU‐8 membrane integrated into a polydimethylsiloxane (PDMS) structure. Intracellular delivery occurred by diffusion as single‐cells are rapidly sheared through the vertical constrictions. The platform demonstrates dextran (4–40‐kDa) delivery into an adherent (HeLa) and a suspension (Jurkat) cell line at throughputs up to 3 million cells min<sup>−1</sup>. The device also delivers small interfering ribonucleic acid (siRNA) and plasmids into primary human mesenchymal stem cells (hMSCs) and human gingival fibroblasts (hGFs), validating its potential for therapeutic applications. The delivery results are analyzed using “image cytometry”—which combines instance segmentation with a rule‐based image processing system. The automated evaluation of single‐cell states, such as cell diameter and fluorescence intensity, is done, which evaluates cell diameter distribution and fluorescence variation within an experimental sample. Quantification of a mechanoporation‐based intracellular delivery at a single‐cell resolution is performed with an automated deep learning (DL)‐based analysis system.
Combinatorial and Alternating Droplet Printing with Self-regulating Pen-needle-based Micronozzle
2025-07
Muhammad Awais Maqbool, Muhammad Zohaib Maqbool, Shunya Okamoto, Takayuki Shibata, Tuhin Subhra Santra, Moeto Nagai
掲載先 / Source: MRS Advances
発行者 / Publisher: Springer Nature
Vol.: 10
Type: scientific_journal
査読あり / Peer reviewed国際誌 / International journal国際共著 / International collaborationDistance-Dependent Spatial Analysis of Micropattern-Generated Shockwave for Cell-Type Specific Intracellular Delivery
2025-06
Aniket Mishra, Shunya Okamoto, Takayuki Shibata, Tuhin Subhra Santra, Sangjin Ryu, Moeto Nagai
掲載先 / Source: Biomedical Microdevices
発行者 / Publisher: Springer Nature
Vol.: 27
No.: 30
Type: scientific_journal
査読あり / Peer reviewed国際誌 / International journal国際共著 / International collaborationParallel dilution microfluidic device for enabling logarithmic concentration generation in molecular diagnostics
2025-06
Akira Miyajima, Fumiya Nishimura, Daigo Natsuhara, Yuka Kiba, Shunya Okamoto, Moeto Nagai, Tadashi Yamamuro, Masashi Kitamura, Takayuki Shibata
掲載先 / Source: Lab on a Chip
Vol.: 25
Type: scientific_journal
Pages: 3242–3253
査読あり / Peer reviewed国際誌 / International journal説明・概要 / Description
In this study, we present a genetic diagnostic device with a four-stepwise logarithmic dilution capability for rapid and reliable detection of target nucleic acids in a single operation using the colorimetric loop-mediated isothermal amplification (LAMP) method. An innovative feature is the confluent point with differing microchannel heights ensuring the synchronized inflow of liquids while preventing backflow, even under large volumetric flow rate variations (10-10,000-fold). This enabled the independent generation of each dilution factor under constant pressure.
Light-controlled spatiotemporal manipulation of Euglena gracilis in microfluidic channels
2025-06
Pulasta Chakrabarty, Ryoga Ono, Takuya Kohno, Shunya Okamoto, Takayuki Shibata, Tuhin Subhra Santra, Moeto Nagai
掲載先 / Source: Sensors and Actuators A: Physical
発行者 / Publisher: Elsevier BV
Vol.: 387
Type: scientific_journal
Pages: 116414–116414
査読あり / Peer reviewed国際誌 / International journal国際共著 / International collaborationDevelopment of an autonomous picoliter droplet array generating device with a centrifugal microfluidic system
2025-06-04
Shunya Okamoto, Shota Nakamura, Ayumu Oshita, Moeto Nagai, Takayuki Shibata
掲載先 / Source: Microfluidics and Nanofluidics
発行者 / Publisher: Springer Science and Business Media LLC
Vol.: 29
No.: 7
Type: scientific_journal
査読あり / Peer reviewed国際誌 / International journal説明・概要 / Description
In this study, we propose and develop an autonomous picoliter droplet array-generating device using a centrifugal microfluidic system. Droplet arrays play a crucial role in the advancement of chemical analyses, such as digital quantification and digital PCR. In digital quantification, it is important to standardize the size of the droplets and ensure the ease of analysis of the detection reactions within each droplet. Hence, we developed a device that can form droplets of a predetermined size within pre-arranged cup structures simply by flowing liquid and successfully controlled the flow for generating picoliter droplet arrays. The flow control was conducted simply by rotation, and it was not necessary to customize the centrifuge. By optimizing the cup arrangement and these spaces, the device realized that approximately140 pL of highly uniform droplets with an area concentration as high as 32 pieces per square millimeter. Moreover, by implementing an evaporation-prevention function, it was confirmed that the droplets could be retained for more than 30 min. Owing to its simplicity, it is expected to make a significant contribution to the widespread adoption of digital quantification and advancement of analysis.
PDMS SlipChip: Optimizing Sealing, Slipping, and Biocompatibility Using Low-Viscosity Silicone Oils
2025-04
Rafia Inaam, Marcela Fabiana Bolontrade, Shunya Okamoto, Takayuki Shibata, Tuhin Subhra Santra, Moeto Nagai
掲載先 / Source: Micromachines
発行者 / Publisher: MDPI
Vol.: 16
No.: 5
Type: scientific_journal
査読あり / Peer reviewed国際誌 / International journal国際共著 / International collaborationProposal of a Rapid Detection System Using Image Analysis for ELISA with an Autonomous Centrifugal Microfluidic System
2024-11
Shunya Okamoto, Yuto Mori, Shota Nakamura, Yusuke Kanai, Yoshiaki Ukita, Moeto Nagai, Takayuki Shibata
掲載先 / Source: Micromachines
Vol.: 15
No.: 11
Type: scientific_journal
査読あり / Peer reviewed国際誌 / International journal