Advanced Lab-on-Chip and Micro-Systems for Manipulation and Bio-Detection

A special issue of Biosensors (ISSN 2079-6374). This special issue belongs to the section "Biosensor and Bioelectronic Devices".

Deadline for manuscript submissions: 30 June 2026 | Viewed by 18698

Special Issue Editors

Liaoning Key Laboratory of Marine Sensing and Intelligent Detection, Department of Information Science and Technology, Dalian Maritime University, Dalian 116026, China
Interests: dielectrophoresis; microfluidics; lab-on-chip; particle manipulation and separation
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Guest Editor
Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050, China
Interests: microfluidics; micro/nano-fabrication; smart materials; surface modification; biomimetic sensors and systems
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

To achieve the precise manipulation and detection of micro- and nanotargets, LOC micro-systems provide promising options due to their applications in mechanical, medical, biological, and environmental fields. In all these areas, the adoption of microfluidic devices transforms the efficiency of the reactive process or assay and analytical throughput. For biological and chemical applications, there is great interest in micro/nano-structured channel systems and micro/nano-patterned surfaces. So-called microfluidic devices offer great prospects for carrying out biochemical reactions, as well as successive separation and analysis of the reaction products on one chip. In this Special Issue, entitled “Advanced Lab-on-Chip and Micro-Systems for Manipulation and Bio-Detection”, we seek to showcase research papers, communications, and review articles that focus on novel methodological developments by using advanced microfluidic systems for sampling and detection, with particular interest being paid to techniques for the manipulation, separation, characterization, and identification of micro-targets. Based on their ability to perform complex experimental workflows in a rapid, efficient, and robust fashion, the platforms are favorable for defined biological and chemical applications.

Dr. Kai Zhao
Dr. Kaihuan Zhang
Guest Editors

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Keywords

  • microfluidics
  • LOC devices
  • dielectrophoretic
  • microfabrication
  • target manipulation
  • signal detection
  • resolution and throughput

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Published Papers (5 papers)

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Research

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11 pages, 3028 KB  
Article
Efficient On-Chip Separation and Labeling of Extracellular Vesicles from Whole Blood
by Jian Feng, Zhichen Li, Haoyang Shen, Rui Hao, Yifei Yang, Xi Chen, Xin Hong, Guoqiang Gu, Lin Zeng and Hui Yang
Biosensors 2026, 16(4), 220; https://doi.org/10.3390/bios16040220 - 14 Apr 2026
Viewed by 261
Abstract
The development of high-throughput technologies for the separation and labeling of extracellular vesicles (EVs) from whole blood is critical for downstream EV detection and analysis. However, conventional EV separation and labeling workflows are typically labor-intensive and inefficient, requiring multiple sequential processing steps. Here, [...] Read more.
The development of high-throughput technologies for the separation and labeling of extracellular vesicles (EVs) from whole blood is critical for downstream EV detection and analysis. However, conventional EV separation and labeling workflows are typically labor-intensive and inefficient, requiring multiple sequential processing steps. Here, we present a microfluidic platform that integrates negative magnetophoresis-based separation with mixing-enhanced on-chip labeling. The chip adopts a vertical flow channel architecture in combination with a Halbach-array magnetic field configuration, thereby overcoming the throughput limitations inherent to traditional horizontal microchannels. Parallel channels can be freely arranged above on the magnetic array to achieve ultra-high throughput processing, achieving a cell removal efficiency of 99.97% at a blood-to-sheath flow ratio of 1:5. Furthermore, by incorporating a narrow-wide channel design synergized with a herringbone–Tesla micromixer structure, the platform achieves a labeling efficiency of 91.8% within 2 min, approaching the performance of conventional 20 min incubation. This system offers both high-throughput and integration capabilities, providing a powerful technical platform for EV-related life science research. Full article
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19 pages, 3043 KB  
Article
Human Gut–Brain Interaction Chip for Dissecting the Gut-Derived LPS and Butyrate Regulation of the Blood–Brain Barrier
by Ranran Yan, Ge Gao, Yulin Deng, Jinhua Li and Yujuan Li
Biosensors 2026, 16(1), 23; https://doi.org/10.3390/bios16010023 - 29 Dec 2025
Viewed by 892
Abstract
The gut–brain axis (GBA) interaction is important for human health and disease prevention. Organ chips are considered a solution for GBA research. Three-dimensional (3D) cultures and microfluidics engineered in an organ chip could improve the scientific knowledge in the GBA interactions field. In [...] Read more.
The gut–brain axis (GBA) interaction is important for human health and disease prevention. Organ chips are considered a solution for GBA research. Three-dimensional (3D) cultures and microfluidics engineered in an organ chip could improve the scientific knowledge in the GBA interactions field. In this study, a novel organ chip is developed, which achieves multicellular three-dimensional cultivation by utilizing a decellularized matrix. In addition, this paper reports the rapid prototyping process of the GBA microfluidic chip in polydimethylsiloxane (PDMS) using 3D printing interconnecting poly(ethylene/vinyl acetate) (PEVA) microchannel templates. In comparison to the static culture system of the transwell model, the intestinal epithelial barrier (IEB) and blood–brain barrier (BBB) models on our chip demonstrated superior barrier function and the efflux functionality of transporters under appropriate fluidic conditions. Additionally, it is observed that butyrate protected against BBB dysfunction induced by gut-derived lipopolysaccharide (LPS) via enhancing intestinal barrier function. These results demonstrate that this multicellular, three-dimensional cultivation integrated with a fluidic shear stress simulation chip offers a promising tool for gut–brain interaction study to predict therapy of intestinal and neurological disorders. Full article
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Review

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37 pages, 2901 KB  
Review
Organs-on-Chips in Drug Development: Engineering Foundations, Artificial Intelligence, and Clinical Translation
by Nilanjan Roy and Luca Cucullo
Biosensors 2026, 16(3), 155; https://doi.org/10.3390/bios16030155 - 11 Mar 2026
Viewed by 1503
Abstract
Organ-on-a-chip (OoC) technologies, also termed microphysiological systems (MPSs), integrate microfluidics, engineered biomaterials, human-derived cells, and on-chip biosensing to model human physiology in microscale devices that deliver quantitative, time-resolved readouts. This review surveys the 2010–2025 literature, emphasizing how sensing, standardized sampling, and analytics enable [...] Read more.
Organ-on-a-chip (OoC) technologies, also termed microphysiological systems (MPSs), integrate microfluidics, engineered biomaterials, human-derived cells, and on-chip biosensing to model human physiology in microscale devices that deliver quantitative, time-resolved readouts. This review surveys the 2010–2025 literature, emphasizing how sensing, standardized sampling, and analytics enable clinical concordance and fit-for-purpose regulatory use. We synthesize advances in (i) materials, fabrication, and microfluidic design; (ii) organ- and disease-focused case studies; and (iii) translational benchmarks that align chip outputs with clinical pharmacokinetics, toxicology, and biomarker datasets. Across organ systems, platforms increasingly incorporate vascularization, immune components, and organoid hybrids, paired with real-time measurements of barrier integrity, metabolism, electrophysiology, and secreted biomarkers using impedance (TEER), electrochemical, and optical modalities. Representative benchmarking studies report cardiac OoCs achieving AUROC ≥ 0.85 for torsadogenic risk classification, and renal chips improving prediction of transporter-mediated clearance relative to conventional in vitro assays. We summarize validation approaches and regulatory developments relevant to new approach methodologies, including the FDA Modernization Act 2.0, and discuss how AI and multi-omics can automate signal and image analysis, harmonize cross-platform datasets, and support digital-twin workflows that couple OoC measurements to in silico models. Overall, biosensor-enabled OoCs are progressing toward quantitatively benchmarked platforms for safety pharmacology, ADME/PK–PD, and precision medicine. Full article
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18 pages, 4824 KB  
Review
Review of Microchip Analytical Methods Coupled with Aptamer-Based Signal Amplification Strategies for High-Sensitivity Bioanalytical Applications
by Xudong Xue, Yanli Hou, Caihua Hu and Yan Zhang
Biosensors 2025, 15(10), 653; https://doi.org/10.3390/bios15100653 - 1 Oct 2025
Cited by 1 | Viewed by 909
Abstract
Aptamers have many advantages, including facile synthesis and a high affinity and good selectivity toward their targets. Therefore, aptamer-based biosensors have become increasingly popular for the detection of different bioanalytical substances. Microchip-based analytical detection platforms offer significant advantages for the detection of different [...] Read more.
Aptamers have many advantages, including facile synthesis and a high affinity and good selectivity toward their targets. Therefore, aptamer-based biosensors have become increasingly popular for the detection of different bioanalytical substances. Microchip-based analytical detection platforms offer significant advantages for the detection of different analytes, including their ease of operation, high throughput, cost-effectiveness, and high sensitivity. Aptamer-based signal amplification techniques have been combined with microchips to sensitively detect bioanalytical substances due to their stable reactions, easy operation, and specificity in biomedical science and environmental fields. This review summarizes representative articles about aptamer signal amplification strategies on microchips for the detection of bioanalytical substances, as well as their advantages and challenges for specific applications. We highlight the accomplishments and shortcomings of aptamer signal amplification strategies on microchips and discuss the direction of development and prospects of aptamer signal amplification strategies on microchips. Full article
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37 pages, 7820 KB  
Review
Recent Advances in Dielectrophoretic Manipulation and Separation of Microparticles and Biological Cells
by Junzhu Yao, Kai Zhao, Jia Lou and Kaihuan Zhang
Biosensors 2024, 14(9), 417; https://doi.org/10.3390/bios14090417 - 27 Aug 2024
Cited by 25 | Viewed by 11885
Abstract
Dielectrophoresis (DEP) is an advanced microfluidic manipulation technique that is based on the interaction of polarized particles with the spatial gradient of a non-uniform electric field to achieve non-contact and highly selective manipulation of particles. In recent years, DEP has made remarkable progress [...] Read more.
Dielectrophoresis (DEP) is an advanced microfluidic manipulation technique that is based on the interaction of polarized particles with the spatial gradient of a non-uniform electric field to achieve non-contact and highly selective manipulation of particles. In recent years, DEP has made remarkable progress in the field of microfluidics, and it has gradually transitioned from laboratory-scale research to high-throughput manipulation in practical applications. This paper reviews the recent advances in dielectric manipulation and separation of microparticles and biological cells and discusses in detail the design of chip structures for the two main methods, direct current dielectrophoresis (DC-DEP) and alternating current dielectrophoresis (AC-DEP). The working principles, technical implementation details, and other improved designs of electrode-based and insulator-based chips are summarized. Functional customization of DEP systems with specific capabilities, including separation, capture, purification, aggregation, and assembly of particles and cells, is then performed. The aim of this paper is to provide new ideas for the design of novel DEP micro/nano platforms with the desired high throughput for further development in practical applications. Full article
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