Lab on a ChipPub Date : 2026-09-07DOI: 10.1039/d6lc00458j
Jianfeng Chen,Ke Li,Yichuan Di,Feifan Hu,Yaqi Nie,Xiaoshan Jin,Xiaoxiao Chen,Mengxian Zhang,Meirong Yi
{"title":"A piezoelectric ultrasound-assisted microjetting platform for high-throughput intracellular delivery","authors":"Jianfeng Chen,Ke Li,Yichuan Di,Feifan Hu,Yaqi Nie,Xiaoshan Jin,Xiaoxiao Chen,Mengxian Zhang,Meirong Yi","doi":"10.1039/d6lc00458j","DOIUrl":"https://doi.org/10.1039/d6lc00458j","url":null,"abstract":"Efficient intracellular delivery of biomacromolecules and nanomaterials requires transient membrane permeabilization while preserving high cell viability, cell recovery, and processing throughput. However, conventional carrier-mediated delivery, electroporation, and passive mechanical extrusion approaches are often constrained by cargo-size limitations, cytotoxicity, limited processing throughput, or channel clogging. Here, we report a piezoelectric ultrasound-assisted microjetting platform for high-throughput, carrier-free intracellular delivery. The platform integrates a high-frequency piezoelectric actuator with a tapered micropore, enabling active ejection of cell suspensions through the nozzle. During microjetting, cells experience localized mechanical perturbation while passing through the micropore and undergo secondary deformation within the ejected droplets, which may promote transient membrane permeabilization. In addition, intra-droplet vortical flow may facilitate local cargo transport toward the cell membrane during the transient membrane-resealing window. Using this platform, we achieved efficient delivery of dextrans with different molecular weights (4–200 kDa), large plasmid DNA (9.3 kbp), polymer nanoparticles (100 nm), and quantum dots across multiple cell types while maintaining high cell viability and recovery. Under optimized conditions, the platform achieved delivery efficiencies of up to 86% and a processing throughput of up to 5 × 107 cells per min. These results suggest that piezoelectric ultrasound-assisted microjetting offers a clogging-resistant strategy with potential for future scale-up in carrier-free intracellular delivery of biomacromolecules and nanomaterials.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"30 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148899084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Closed-Loop Optoelectronic Tweezers System for Programmable Multi-Particle Manipulation and Dynamic Configuration Reconstruction","authors":"Shunxiao Huang,Wenyan Niu,Jingwen Ye,Ao Wang,Ziyi Wang,Caiding Ni,Zijin Zeng,Zaiyang Chen,Hongyan Sun,Chan Li,Yingjian Guo,Shuzhang Liang,Zhijun Zhao,Lin Feng","doi":"10.1039/d6lc00534a","DOIUrl":"https://doi.org/10.1039/d6lc00534a","url":null,"abstract":"Optoelectronic tweezers provide a powerful means for manipulating microscopic objects with low optical power, yet their practical throughput remains constrained because the manipulation time typically increases with the number of targets.Here, we demonstrate a scalable strategy for parallel optoelectronic tweezers manipulation that enables independent yet coordinated control of multiple particles while maintaining near-constant operation time as system size increases. Through real-time adaptive coordination of particle motion and dynamic light-field allocation, the platform simultaneously transports, assembles, and reconfigures multiple targets within a unified framework. Experiments show that the total manipulation time remains nearly unchanged from 1 to 18 particles (32.0 ± 5 s) and achieves more than 90% time reduction relative to conventional serial operation for particle numbers exceeding 20, while maintaining micrometer-scale positioning accuracy (1.63-2.61 μm). Beyond high-throughput transport, the approach enables the programmable assembly of complex structures and continuous multi-round topological reconfiguration with preserved synchronization and structural integrity.By decoupling manipulation efficiency from target number, this work advances optoelectronic tweezers from sequential object handling toward scalable microsystem control and establishes a foundation for reconfigurable cell arrays, microrobotic swarms, and dynamic microsystems.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"35 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148899083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Parallel Hierarchical Gene Assembly from Oligonucleotide Pools on an Integrated Digital Microfluidic Platform","authors":"Yu Guo,Chang Yu,Weihu Hu,Subee Tan,Yiming Dong,Xin Zhao,Dan Wu","doi":"10.1039/d6lc00428h","DOIUrl":"https://doi.org/10.1039/d6lc00428h","url":null,"abstract":"We report an integrated electrowetting-on-dielectric (EWOD) digital microfluidic (DMF) platform for automated gene assembly directly from oligonucleotide pools (OPs). The system is implemented on a glass chip with through-glass vias (TGVs), enabling dense, individually addressable electrodes for programmable droplet manipulation and integrated thermal control for enzymatic reactions. Barcode probes immobilized on a disposable top plate enable sequence-specific capture, spatial partitioning, and on-chip release of oligonucleotides for polymerase cycling assembly (PCA). The platform supports single-round assembly of ~1.2 kb fragments and enables hierarchical two-round assembly of ~1.8 kb products from a common OP, whereas direct single-round assembly of longer targets fails. This work establishes TGV-based DMF as a programmable and scalable platform for low-volume, automated, and hierarchical gene assembly from oligonucleotide pools.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"70 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148893380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A hand-powered positive pressure-driven sample injection digital RPA-CRISPR-Cas12a chip","authors":"Mengda Liang,Juxin Yin,Xutong Shi,Dexiong Xia,Wen Zong,Haiqin Hu,Ningkang Xie,Yulai Li,Shaowu Lv","doi":"10.1039/d6lc00542j","DOIUrl":"https://doi.org/10.1039/d6lc00542j","url":null,"abstract":"Chamber-based digital nucleic acid assays allow absolute quantification with high analytical sensitivity, However, sample introduction and digital discretization mainly relies on negative pressure drive, and this injection method limits its application, especially in on-site detection. but their use outside laboratory settings is still limited by the way samples are partitioned, which often depends on vacuum systems, centrifugation or specialized actuation. Positive-pressure loading is simple and well suited to portable operation, yet it is difficult to apply directly to chamber-based digital assays because air backflow and sample trailing can disrupt stable compartmentalization. This study proposed a hand-powered positive pressure-driven sample injection digital RPA-CRISPR-Cas12a chip for on-site food-safety testing. In this study, these two problems were addressed by combining photocurable oil fixation with branch-channel optimization, enabling rapid and stable discretization in a 15,120 chamber-based microfluidic digital chip using only a hand-operated syringe. Sample loading and partitioning were completed within 2 min without vacuum or centrifugal loading equipment. After integration with a one-pot digital RPA–CRISPR–Cas12a assay targeting hlyA, the system achieved absolute quantification of Listeria monocytogenes with a detection limit of 100 copies μL⁻¹ and good linearity across dilutions (R² = 0.99973). The tests conducted on the milk samples containing the standard substances further proved that this method can be used for on-site testing under resource-limited conditions. Overall, this study provides a feasible strategy for implementing positive-pressure digitization in portable chamber-based digital microfluidic system, which expands the utility of chamber-based digital assays for portable and instrument-free on-site food-safety testing.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"47 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148877465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lab on a ChipPub Date : 2026-09-02DOI: 10.1039/d6lc00581k
Julia Radzio,Stephanie J Yang,Paulo E. Arratia,David Issadore
{"title":"Viscoelasticity-dependent, deformation-based sorting of microgels using sequential bifurcations","authors":"Julia Radzio,Stephanie J Yang,Paulo E. Arratia,David Issadore","doi":"10.1039/d6lc00581k","DOIUrl":"https://doi.org/10.1039/d6lc00581k","url":null,"abstract":"Droplet-based microfluidics have accelerated the discovery of rare variants in large combinatorial protein libraries by enabling high-throughput screening in miniaturized reaction systems. However, throughput limitations and assay compatibility constrain the accessible sequence space and the diversity of enzyme classes amenable to droplet-based screening. Passive, deformability-based sorting systems offer scalability via microfluidic parallelization, but existing platforms lack the sensitivity and throughput required for efficiently exploring vast fitness landscapes. In this work, we present a microfluidic device for passively sorting monodisperse microgels based on their deformability using sequential bifurcations, with a throughput up to 300 Hz. Extension-dominated flow in a T-shaped junction enables rapid microgel deformation, leading to viscoelasticity-dependent trajectories under finite flow inertia. To investigate the relationship between microgel viscoelasticity and sorting performance, we characterized the transit dynamics of a model system of agarose microgels. We demonstrated the ability to rapidly isolate highly viscous agarase-degraded microgels from highly elastic 1% agarose microgels with 99.3% accuracy. Our design has promise for expanding the capabilities of droplet-based screening for enzyme-mediated polymerization or degradation assays.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"4 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148877532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lab on a ChipPub Date : 2026-08-27DOI: 10.1039/d6lc00562d
Ran Tao,Nathaniel C Esteves,Jun Zhu,Arnold Mathijssen
{"title":"Elongation suppresses rheotaxis and enables microfluidic enrichment of β-lactam-resistant bacteria","authors":"Ran Tao,Nathaniel C Esteves,Jun Zhu,Arnold Mathijssen","doi":"10.1039/d6lc00562d","DOIUrl":"https://doi.org/10.1039/d6lc00562d","url":null,"abstract":"Antimicrobial resistance (AMR) complicates the treatment of diseases including lung and urinary tract infections (UTIs), which are among the most common bacterial infections worldwide. Motile pathogens can use rheotaxis to swim upstream against fluid flows, potentially promoting access to upper regions of anatomical tracts. However, it remains unclear how antibiotic exposure and resistance influence this transport process. Here, using single-cell tracking microscopy, we investigate how elongation induced by β-lactam antibiotics affects the rheotactic migration of E. coli in confined microfluidic channels. Remarkably, we find that rheotaxis can be inhibited 100-fold by antibiotics, even if the susceptible elongated cells remain fully motile. However, resistant bacteria remain short and retain upstream migration under the same conditions. Using genetically engineered bacteria with tunable cell length, we show that the underlying mechanism that governs rheotaxis is the coupling between cell morphology and flow vorticity, where elongated cells are rapidly rotated downstream. Finally, we exploit this length-dependent transport difference to separate short and elongated cells under flow and enrich ampicillin-resistant cells from mixed populations. Together, these results establish bacterial elongation as a key control parameter for rheotactic transport, and provide a proof-of-concept strategy for enriching β-lactam-resistant bacteria for potential use in rapid AMR detection.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"53 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148853835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lab on a ChipPub Date : 2026-08-27DOI: 10.1039/d6lc00576d
Mitch de Waard,Ignaas Jimidar,Valentina Biagioni,Han J.G.E. Gardeniers,Stefano Cerbelli,Gert Desmet
{"title":"Towards a Brownian Sieving device for Nanoparticle Size Separations †","authors":"Mitch de Waard,Ignaas Jimidar,Valentina Biagioni,Han J.G.E. Gardeniers,Stefano Cerbelli,Gert Desmet","doi":"10.1039/d6lc00576d","DOIUrl":"https://doi.org/10.1039/d6lc00576d","url":null,"abstract":"We report on a preliminary study to test the liquid flow and particle diffusion properties in a device developed to deliver a proof-of-principle for so-called Brownian sieve-enforced Hydrodynamic Chromatography (BS-HDC). This is a recently proposed novel separation principle to enhance the selectivity and efficiency of conventional HDC by combining it with a size sieving step through a micro-or nano-perforated separating wall interfacing a central feed channel to a peripheral auxiliary channel, characterized by a different average velocity, that can only accept the small particles in the sample. We demonstrate the feasibility to fabricate a proof-of-principle device with a 400 nm sieving gap, and report on the flow and diffusion tests that were carried out with a fluorescent marker. These tests demonstrate the magnitude of the velocity fields and the transport across the nano-gaps between the central and peripheral auxiliary channel, which perfectly match with theoretical expectations. Specifically, transport across the nano gaps is dominated by molecular diffusion. Nanosieving experiments with 235 and 563 nm particles showed the ability to selectively transport the smaller particles through the nano-sieving gaps while the larger particles remained in the central feed channel with a 100% selectivity. However, the observed fluxes were found to be strongly influenced by local convective flows opposing the diffusive transport near the in-and outlet of the channels, a phenomenon we think can be owed to the presence of persistent air bubbles in the flow distributors creating undesirable pressure fluctuations.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"32 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148853836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lab on a ChipPub Date : 2026-08-26DOI: 10.1039/d5lc01038a
Lena Bauernhofer,Jasmin Baron,Sandro Keller,Georg Krainer
{"title":"Microfluidic Diffusional Sizing in Bioanalysis and Biosensing","authors":"Lena Bauernhofer,Jasmin Baron,Sandro Keller,Georg Krainer","doi":"10.1039/d5lc01038a","DOIUrl":"https://doi.org/10.1039/d5lc01038a","url":null,"abstract":"Microfluidic diffusional sizing (MDS) has emerged as a versatile lab-on-a-chip technology for quantitative analysis of biomolecules in solution, particularly for determining particle sizes and characterizing biomolecular interactions. By measuring the diffusive behavior of molecules under laminar flow in a microfluidic chip, MDS enables the precise determination of hydrodynamic radii and binding affinities, even in complex biological samples, while requiring only minute sample volumes. As a result, MDS is establishing itself as a key tool in the life sciences. This review summarizes recent advances and applications of MDS in the context of bioanalysis and biosensing. We outline the fundamental principles of MDS and highlight its wide range of applications, including studies of protein aggregation, antibody affinity profiling, protein–lipid interactions, and nanoparticle sizing. We further discuss recent technological developments, such as single-molecule detection, label-free strategies, and multidimensional analysis, that have significantly expanded the scope, sensitivity, and utility of MDS. We conclude with an outlook on the anticipated impact of MDS on biomedical research, diagnostics, and therapeutic development.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"33 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148853837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lab on a ChipPub Date : 2026-08-25DOI: 10.1039/d5lc01169h
Anthony Lefebvre, Wataru Hanamoto, Jongho Park, Pascal Deleporte, Anne-Sophie Dewalle, Vincent Senez, Orégane Bajeux, Nicolas Stoup, Guillaume Paul Grolez, Laurent Mortier, Nadira Delhem, Beomjoon Kim
{"title":"Development of dual-function optical microneedle lens array for skin cancer treatment by photodynamic therapy.","authors":"Anthony Lefebvre, Wataru Hanamoto, Jongho Park, Pascal Deleporte, Anne-Sophie Dewalle, Vincent Senez, Orégane Bajeux, Nicolas Stoup, Guillaume Paul Grolez, Laurent Mortier, Nadira Delhem, Beomjoon Kim","doi":"10.1039/d5lc01169h","DOIUrl":"10.1039/d5lc01169h","url":null,"abstract":"<p><p>Skin cancer is among the most prevalent cancers worldwide, with melanoma accounting for most skin cancer-related deaths owing to its aggressiveness and metastatic potential. Although treatments including surgery, radiotherapy, immunotherapy, and targeted therapy have improved outcomes, therapeutic limitations persist, particularly in locally advanced or recurrent disease. Photodynamic therapy (PDT), which combines a photosensitizer (PS), light activation, and oxygen to produce reactive oxygen species (ROS) inducing tumor cell death and antitumor immunity, offers a minimally invasive treatment alternative. Despite its clinical success for superficial basal cell carcinoma, PDT efficacy declines for lesion with increased thickness due to a poor PS and limited light penetration through the heterogeneous skin structure. To address these challenges, microneedles (MNs) have emerged as an effective drug delivery tool that can bypass the stratum corneum. Solid, transparent MNs can also guide and concentrate light. Previous studies have suggested combining MNs with lens arrays (optical microneedle lens array, OMLA) to enhance light delivery deeper into the tissues. In this study, we present a novel OMLA device that integrates aligned lenses and coated MNs for the dual delivery of the PS and light. An OMLA fabricated from polylactic-acid (PLA) <i>via</i> hot embossing was mechanically characterized for insertion capability. Computational analysis was used to evaluate light propagation properties, which were validated in an <i>ex vivo</i> human NativeSkin® model. Additionally, we coated two clinically relevant PSs, 5-aminolevulinic acid and rose bengal. Finally, we demonstrated that a PS-coated OMLA effectively delivered both light and the PS, resulting in effective PDT-induced cytotoxicity in 2D and 3D melanoma cell models.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":"4705-4723"},"PeriodicalIF":6.3,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148596611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A versatile microfluidic electrochemical platform for diffusion-controlled, quasi-one-dimensional interfacial studies.","authors":"Shreyanshu Agrawal, Alexander Saperstein, Farzam Zoueshtiagh, Ranga Narayanan, Kirk J Ziegler","doi":"10.1039/d6lc00427j","DOIUrl":"10.1039/d6lc00427j","url":null,"abstract":"<p><p>We present a quasi-one-dimensional microfluidic electrochemical platform that suppresses convection through microscale confinement and eliminates electric field singularities by combining thin film electrodes with a dielectric overhang that shields the top surface of the electrode. This is important as dynamic electrochemical processes emerge from the coupled interplay between ion transport and interfacial kinetics, yet most experimental configurations cannot simultaneously enforce diffusion-dominated conditions and directly visualize the evolving interface. Electrostatic simulations identify an optimal overhang length range that minimizes field intensity and angle variations while maintaining mechanical stability, yielding an approximately equipotential electrode with field lines nearly normal to the interface. To demonstrate the concept, we fabricate a representative device using sputtered Cu/W electrodes and a low stress, pinhole free dielectric stack of alumina and silicon nitride. Using copper electrodeposition as a model system, <i>in situ</i> optical imaging tracks morphological evolution and front motion, while difference image analysis enables quantitative verification of mass conservation between anodic dissolution and cathodic growth under diffusion-dominated conditions. Cells incorporating the dielectric overhang exhibit mass balances consistent with quasi-one-dimensional transport. This modular architecture, compatible with different metal-electrolyte-dielectric combinations and advanced imaging modalities, provides a versatile platform to systematically investigate transport and interfacial phenomena in electrochemical systems.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":"4639-4650"},"PeriodicalIF":6.3,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148596677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}