Soo Hyeon Kim

Direct detection of rare nucleic-acid targets without molecular amplification requires specific recognition events to be made observable while remaining distinguishable from nonspecific interactions. Here, we introduce a microbead-based heterodimer assay (MBHA) that converts two-site recognition of single-stranded DNA into spatially resolved, two-color bead-pairing events for direct nucleic-acid detection. Two spectrally distinct microbead populations are functionalized with partially double-stranded DNA probes exposing target-binding domains complementary to separate regions of the target. Target-mediated bridging produces heterotypic bead pairs that are classified by fluorescence identity and an interparticle-distance criterion, while residual background is evaluated relative to blank measurements. Under the tested conditions, 166 fM was the lowest target concentration exceeding the blank-derived detection threshold. A sequence-scrambled synthetic non-target DNA remained below threshold across the tested concentration range, and detection at 166 fM was retained in the presence of 1 µM non-target DNA, corresponding to an approximately six-million-fold molar excess. Probe redesign further extended the assay to a second 60-nucleotide synthetic DNA target derived from the SARS-CoV-2 ORF1ab sequence. This proof-of-concept study establishes heterodimer counting as an amplification-free measurement strategy in which rare molecular-recognition events are made directly observable and individually classifiable without increasing target copy number.

Swarm robotics relies on robots with minimal sensing and computation that achieve self-organization at the level of the collective to address a variety of tasks. Yet, swarm robotics still struggles with global tasks that require understanding the broader spatial context in which robots operate, such as identifying the shape of the arena in which they are embedded. Here, we introduce spectral swarm robotics, a framework in which robots recover global spectral descriptors of the swarm’s geometric structure through strictly local interactions. To do so, robots emulate diffusion to locally estimate Laplacian spectral invariants, quantities normally obtained only through centralized computation. These spectral values serve as compact descriptors of the environment. In the present proof of concept, robots estimated the second Laplacian eigenvalue, λ ₂ , and used it to classify arenas from a predefined set of shapes with distinct spectral signatures. We show that estimating a single eigenvalue is sufficient for one-shot classification among selected confined environments with distinct spectral signatures. We uncovered a scaling law linking swarm size (a global parameter) and interaction radius (a local parameter) that ensures robust estimation. We validated the approach experimentally on two distinct hardware platforms, Kilobots and Pogobots, achieving reliable classification of arena shapes under realistic noise and sparse connectivity conditions. Last, we discuss how locally recovering Laplacian spectral invariants opens avenues for swarm robotics in settings where producing efficient collective behaviors strongly depends on the global structure of the swarm.

To understand how individual cells interact with other cell types, cell–cell interactions must be investigated at the single-cell level. Here, we propose a novel microfluidic device, termed a trap-and-drop microwell array, for single-cell culture and deterministic pairing of single cells. Deterministic single-cell pairing is achieved by sequentially trapping single cells in an electroactive microwell array using dielectrophoresis, fabricated at the ceiling of a microfluidic channel, and subsequently transferring the trapped cells into polydimethylsiloxane cell culture microwells located beneath each electroactive microwell. By separating the functions of microwells for cell trapping and cell culture, the system enables independent optimization of microwell dimensions for efficient trapping and stable cell culture. We successfully demonstrated long-term single-cell culture of U937 cells, and efficient pairing of single cells by sequentially trapping and dropping two different populations of U937 cells, achieving a pairing efficiency of 62%. This system offers promising applications for analyzing long-term cell–cell interactions.

Epithelial tissues form selective barriers essential for physiological homeostasis. Conventional in vitro models rely on solid substrates, which limit the physicochemical flexibility of the cellular microenvironment. Here, we introduce a microfluidic platform in which a collagen-coated liquid–liquid interface formed between perfluorocarbon (FC-43) and culture medium serves as a substrate for epithelial cell adhesion. By culturing Caco-2 cells in the device, we show that the liquid interface supports cell attachment and the formation of monolayers. Immunofluorescence observation reveals the development of tight junctions and organized actin cytoskeletons, indicating early-stage epithelial maturation. Our new microfluidic system enables the formation of stable liquid–liquid interfaces that serve as viable and flexible substrates for epithelial cell culture, offering new opportunities for multiphase microfluidic models of epithelial barriers.

A method to study systematically the mechanical response of a simple DNA nanostar hydrogel evidences - at temperatures much higher than the percolation of the DNA network - a surprising solid behaviour attributed to a glass transition.

DNA nanostar hydrogels are a novel class of biocompatible and programmable materials with promising applications as a cell matrix for tissue engineering or cancer diagnosis. Yet, precise isolation of specific cell types with these hydrogels has remained elusive without specific interaction between DNA and cell membrane. Here, a DNA nanostar hydrogel–based method is reported for cell isolation, achieved by interfacing living cells with the hydrogel via an antibody‐functionalized DNA motif. As a proof of concept, epithelial cell adhesion molecule (EpCAM)‐positive cells are isolated—a model of circulating tumor cells—whose separation from white blood cells is crucial for early cancer diagnosis. By optimizing the antibody‐DNA conjugate, a specific binding is achieved between target cells and the DNA gel, enabling the capture of up to 90% of cells. The cells are selectively enriched from a mixture of different cell types using parallelized and iterative capture. The cells recover by dissociating the gel using strand displacement, retain their viability and capacity to proliferate, which supports their future use for culture or analysis. This generalizable method allows coupling of any cell type to DNA gels —supporting future applications ranging from cancer research to recapitulate cellular tumor models in vitro or regenerative medicine to grow designer tissues.

1細胞解析は世界的に注目を集めており，次世代シーケンサーを用いた網羅的な解析と組み合わせた基礎研究が活発に進められている．しかし，従来の1細胞解析技術は主に培養細胞を対象としており，細胞数が限られる臨床検体などの解析には適していない．本稿では，マイクロ流体デバイスを用いて単一細胞を決定論的に確実に捕捉し，その後，多様な分析を行うことが可能なエレクトロアクティブマイクロウェルアレイ技術の概要と，その医療分野への応用事例について紹介する．さらに，新たな試みとして，電気化学測定による単一細胞分析手法についても述べる．

Bioelectrochemistry is crucial for understanding biological functions and driving applications in synthetic biology, healthcare, and catalysis. However, current simulation methods fail to capture both the stochastic nature of molecular motion and electron transfer across the relevant picosecond-to-minute timescales. We present QBIOL, a web-accessible software that integrates molecular dynamics, applied mathematics, GPU programming, and quantum charge transport to address this challenge. QBIOL enables quantitative stochastic electron transfer simulations and has the potential to reproduce numerically any (bio) electrochemical experiments. We illustrate this potential by comparing our simulations with experimental data on the current generated by electrode-attached redox-labeled DNA, or by nanoconfined redox species, in response to a variety of electrical excitation waveforms, configurations of interest in biosensing and catalysis. The adaptable architecture of QBIOL extends to the development of devices for quantum and molecular technologies, positioning our software as a powerful tool for enabling new research in this rapidly evolving field.

This study presents a novel microfluidic device coupled with a multilayer interconnect Si/SiO² control circuit, named the deterministic single-cell combinatorial reactor, for the highly efficient combination of multiple single cells.