Featured
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Article
| Open Access
Operando investigation of the synergistic effect of electric field treatment and copper for bacteria inactivation
The overuse of chemicals in our disinfection processes has warranted the development of alternatives. Here, authors use a lab-on-a-chip device to study and observe the synergistic effects of electric field treatment and copper for inactivation of bacteria with promising applications in many fields.
- Mourin Jarin
- , Ting Wang
- & Xing Xie
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Article
| Open Access
Visualization-enhanced under-oil open microfluidic system for in situ characterization of multi-phase chemical reactions
Under-oil open microfluidic systems have potential for studying multi-phase chemical reactions but have so far demonstrated largely only for biological applications. Here, the authors report the development of a system for in situ characterization of gas-liquid reactions by Raman spectroscopy.
- Qiyuan Chen
- , Hang Zhai
- & Bu Wang
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Article
| Open Access
Molecular imprinting-based indirect fluorescence detection strategy implemented on paper chip for non-fluorescent microcystin
Fluorescence analysis is a fast and sensitive method for the trace detection of environmental toxins, but it remains challenging to develop a fluorescence method for detecting nonfluorescent toxins. Here, the authors report an indirect fluorescent sensing strategy for the rapid, selective and sensitive detection of the non-fluorescent microcystin as a model target.
- Bowei Li
- , Ji Qi
- & Lingxin Chen
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Article
| Open Access
Capturing nascent extracellular vesicles by metabolic glycan labeling-assisted microfluidics
Temporally sorting EV populations is hard. Here the authors report a microfluidic-based strategy to enable selective isolation of nascent EVs by using azido groups to act as a timestamp for click chemistry labelling: they apply this to mouse models of anti-PD-L1 immunotherapy.
- Qiuyue Wu
- , Wencheng Wang
- & Yanling Song
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Article
| Open Access
A human lung alveolus-on-a-chip model of acute radiation-induced lung injury
Acute exposure to radiation can lead to acute pneumonitis, fibrosis or death. Here the authors develop an alveolus-on chip model to study the molecular characteristics of radiation induced lung injury, better understand radiation induced lung disease and facilitate drug screening.
- Queeny Dasgupta
- , Amanda Jiang
- & Donald E. Ingber
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Article
| Open Access
Droplet-based bisulfite sequencing for high-throughput profiling of single-cell DNA methylomes
Single-cell DNA methylomic studies offer high resolution to differentiate cell subsets based on their epigenomic features. Here, the authors demonstrate Drop-BS, a droplet-based single-cell bisulfite sequencing library preparation method, for DNA methylome profiling.
- Qiang Zhang
- , Sai Ma
- & Chang Lu
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Article
| Open Access
SEC-seq: association of molecular signatures with antibody secretion in thousands of single human plasma cells
Linking proteins secreted from individual cells with other cellular information is challenging. Here, authors report a high-throughput method which uses hydrogel nanovials loaded with single cells to link the secretion profile of individual cells with their surface markers and transcriptomic data.
- Rene Yu-Hong Cheng
- , Joseph de Rutte
- & Richard G. James
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Article
| Open Access
High-throughput single nucleus total RNA sequencing of formalin-fixed paraffin-embedded tissues by snRandom-seq
Formalin-fixed paraffin-embedded (FFPE) tissues constitute a vast and valuable patient material bank, but single nucleus RNAseq using such tissues is challenging. Here the authors develop a droplet-based method called snRandom-seq for high-throughput and sensitive single nucleus RNA-seq of FFPE samples.
- Ziye Xu
- , Tianyu Zhang
- & Yongcheng Wang
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Article
| Open Access
Direct digital sensing of protein biomarkers in solution
There are limitations with current protein sensing methods. Here the authors report DigitISA, a digital immunosensor assay based on microchip electrophoretic separation and single-molecule detection that enables quantitation of protein biomarkers in a single, solution-phase step.
- Georg Krainer
- , Kadi L. Saar
- & Tuomas P. J. Knowles
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Article
| Open Access
An optofluidic platform for interrogating chemosensory behavior and brainwide neural representation in larval zebrafish
Studying chemosensory processing desires precise chemical cue presentation, behavioral response monitoring, and large-scale neuronal activity recording. Here, the authors report a fluidics-based toolkit for studying chemosensation in larval zebrafish, and used it to reveal the brainwide neural representations of cadaverine sensing and its binasal input-dependent behavioral avoidance.
- Samuel K. H. Sy
- , Danny C. W. Chan
- & Ho Ko
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Article
| Open Access
Large-scale perfused tissues via synthetic 3D soft microfluidics
Bioengineering live tissues has remained challenging due to limited nutrient exchange in the growing tissues. Here, the authors have developed micro-perfused 2-photon printing of 3D microfluidics, to engineer large-scale, viable and functional neural and hepatic 3D tissues.
- Sergei Grebenyuk
- , Abdel Rahman Abdel Fattah
- & Adrian Ranga
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Article
| Open Access
Wireless dielectrophoresis trapping and remote impedance sensing via resonant wireless power transfer
The authors use resonant wireless power transfer to remotely trap and release nanoparticles in solution and detect their presence as a shift in impedance in real-time. This is accomplished using the extreme field confinement of a nanogap capacitor.
- Christopher T. Ertsgaard
- , Minki Kim
- & Sang-Hyun Oh
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Article
| Open Access
Biomolecular condensate phase diagrams with a combinatorial microdroplet platform
A central concept for characterising phase-separating systems is the phase diagram but generation of such diagrams for biomolecular systems is typically slow and low-throughput. Here the authors describe PhaseScan, a combinatorial droplet microfluidic platform for high-resolution acquisition of multidimensional biomolecular phase diagrams.
- William E. Arter
- , Runzhang Qi
- & Tuomas P. J. Knowles
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Article
| Open Access
Microfluidic space coding for multiplexed nucleic acid detection via CRISPR-Cas12a and recombinase polymerase amplification
Fast, low-cost and multiplexed nucleic acid detection is challenging. Here the authors report a strategy that couples microfluidic space coding, CRISPRCas12a, and multiplex RPA for the rapid detection of up to 30 targets with only one fluorescent probe.
- Zhichen Xu
- , Dongjuan Chen
- & Maili Liu
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Article
| Open Access
A mid-infrared lab-on-a-chip for dynamic reaction monitoring
Rapid investigation of chemical reactions is a challenge in bio-medical analysis. Here, the authors demonstrate sensitive in-situ real-time reaction-monitoring of conformational changes in protein solution, based on a fingertip-sized mid-IR lab-on-a-chip.
- Borislav Hinkov
- , Florian Pilat
- & Gottfried Strasser
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Perspective
| Open Access
A sound approach to advancing healthcare systems: the future of biomedical acoustics
Acoustic techniques are moving towards the clinic. Here the authors highlight recent developments in the areas of acoustic mechanobiology, point-of-care diagnostics, in vivo manipulation and tissues engineering, and provide their thoughts on the current challenges and directions for future work.
- Joseph Rufo
- , Peiran Zhang
- & Tony Jun Huang
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Article
| Open Access
High resolution microfluidic assay and probabilistic modeling reveal cooperation between T cells in tumor killing
Anti-cancer cytotoxic T cell responses largely vary among individuals. Here authors show, by stochastic modeling on high throughput T cell behavior and matched tumor spheroid fate data generated by a microfluidics system, that tumor killing is dependent on T cell cooperativity, which might contribute to the heterogeneity of T cell responses.
- Gustave Ronteix
- , Shreyansh Jain
- & Charles N. Baroud
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Article
| Open Access
High-throughput production of functional prototissues capable of producing NO for vasodilation
Protoissues have received a lot of attention for studying cell interaction and for biomedical engineering. Here, the authors demonstrate a high-throughput, bottom-up approach to assemble spatial programmable prototissues based on the magnetic Archimedes affect and demonstrate biomedical application for producing NO for vasodilation.
- Xiangxiang Zhang
- , Chao Li
- & Xiaojun Han
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Article
| Open Access
Streamlined single-cell proteomics by an integrated microfluidic chip and data-independent acquisition mass spectrometry
Single-cell proteomics is an emerging approach to characterize cell-to-cell differences. Here, the authors develop chips that enable complete proteomic sample processing down to the single-cell level and integrate them with DIA-MS into a streamlined single-cell proteomics workflow.
- Sofani Tafesse Gebreyesus
- , Asad Ali Siyal
- & Hsiung-Lin Tu
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Article
| Open Access
Massive image-based single-cell profiling reveals high levels of circulating platelet aggregates in patients with COVID-19
The authors report the landscape of circulating platelet aggregates in COVID-19 obtained by massive single-cell image-based profiling and temporal monitoring to elucidate the underlying process of COVID-19-assocaited microvascular thrombosis.
- Masako Nishikawa
- , Hiroshi Kanno
- & Keisuke Goda
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Article
| Open Access
High-throughput and high-efficiency sample preparation for single-cell proteomics using a nested nanowell chip
Single-cell proteomics is an emerging technology but protein coverage, throughput and quantitation accuracy are often still insufficient. Here, the authors develop a nested nanowell chip that improves protein recovery, throughput and robustness of isobaric labeling-based quantitative single-cell proteomics.
- Jongmin Woo
- , Sarah M. Williams
- & Ying Zhu
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Article
| Open Access
Synchronization between peripheral circadian clock and feeding-fasting cycles in microfluidic device sustains oscillatory pattern of transcriptome
Chronic desynchronization between physiological and behavioral rhythms has been linked to the onset of metabolic diseases. Here the authors control the cyclic metabolic signals in a microfluidic device to study the effects of the timing, period and frequency of glucose and insulin on the transcriptome of cultured fibroblasts.
- Onelia Gagliano
- , Camilla Luni
- & Nicola Elvassore
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Article
| Open Access
Physiologic biomechanics enhance reproducible contractile development in a stem cell derived cardiac muscle platform
Investigations of human cardiac disease involving human pluripotent stem cell-derived cardiomyocytes are limited by the disorganized presentation of biomechanical cues resulting in cell immaturity. Here the authors develop a platform of micron-scale 2D cardiac muscle bundles to precisely deliver physiologic cues, improving reproducibility and throughput.
- Yao-Chang Tsan
- , Samuel J. DePalma
- & Adam S. Helms
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Article
| Open Access
A microfluidic platform for highly parallel bite by bite profiling of mosquito-borne pathogen transmission
High-throughput molecular surveillance of mosquitoes carrying dangerous pathogens is currently challenging. Here the authors present Vectorchip, a low-cost microfluidic platform enabling multiplexed detection of mosquito DNA, viral RNA and infectious viral particles at single bite resolution.
- Shailabh Kumar
- , Felix J. H. Hol
- & Manu Prakash
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Article
| Open Access
Measuring kinetics and metastatic propensity of CTCs by blood exchange between mice
Current methods for acquiring dissemination kinetics of rare circulating tumor cells (CTCs) that form metastases have several limitations. Here, the authors show an approach for measuring endogenous CTC kinetics by continuously exchanging CTC-containing blood between un-anesthetized, tumor-bearing mice and healthy, tumor-free counterparts.
- Bashar Hamza
- , Alex B. Miller
- & Scott R. Manalis
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Article
| Open Access
Spatially and optically tailored 3D printing for highly miniaturized and integrated microfluidics
The ever-growing need for highly functional, compact, and integrated microfluidic devices often incurs lengthy and expensive manufacturing processes. Here, authors introduce a generalized 3D printing process that enables fast parallel fabrication of miniaturized, high resolution 3D components.
- Jose L. Sanchez Noriega
- , Nicholas A. Chartrand
- & Gregory P. Nordin
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Article
| Open Access
Measuring expression heterogeneity of single-cell cytoskeletal protein complexes
Existing methods for multimeric protein complex quantification in single cells suffer from limited selectivity and sensitivity. Here the authors report Single-cell protein Interaction Fractionation Through Electrophoresis and immunoassay Readout (SIFTER) and use this to probe the effects of cellular stress.
- Julea Vlassakis
- , Louise L. Hansen
- & Amy E. Herr
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Article
| Open Access
Circulating trophoblast cell clusters for early detection of placenta accreta spectrum disorders
Placenta accreta spectrum (PAS) is a high-risk obstetrical complication associated with significant morbidity and mortality. Here the authors discover a uniquely high prevalence of circulating trophoblasts clusters in PAS and explore their diagnostic potential to augment current diagnostic modalities for the early detection of PAS.
- Yalda Afshar
- , Jiantong Dong
- & Yazhen Zhu
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Article
| Open Access
Guided accumulation of active particles by topological design of a second-order skin effect
Sustainable strategies for shepherding active particles are at the heart of many prospective applications. Here, Palacios et al. use the emerging topological properties of a microfluidic maze array to passively guide self-propelled colloids from the interior to the edges of the device.
- Lucas S. Palacios
- , Serguei Tchoumakov
- & Adolfo G. Grushin
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Article
| Open Access
Oil immersed lossless total analysis system for integrated RNA extraction and detection of SARS-CoV-2
Bottlenecks in qPCR-based COVID-19 diagnostics include the lengthy multistep process and reagent shortages. Here the authors report OIL-TAS which integrates RNA extraction and detection into a single device.
- Duane S. Juang
- , Terry D. Juang
- & David J. Beebe
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Article
| Open Access
Mattertronics for programmable manipulation and multiplex storage of pseudo-diamagnetic holes and label-free cells
Here, the authors present a pseudo-diamagnetophoresis mattertronic approach for programmable manipulation of label-free cells. Immersed in biocompatible ferrofluids, single cells are moved along linear negative micromagnetic patterns, switched at eclipse diode patterns and stored in potential wells.
- Sandhya Rani Goudu
- , Hyeonseol Kim
- & CheolGi Kim
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Article
| Open Access
Microfluidic platform accelerates tissue processing into single cells for molecular analysis and primary culture models
Existing methods for tissue dissociation are inefficient and lead to variable outcomes and biases. Here, the authors present a microfluidic platform that combines digestion, disaggregation and filtration of tissue to allow single cell analysis and RNA sequencing.
- Jeremy A. Lombardo
- , Marzieh Aliaghaei
- & Jered B. Haun
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Article
| Open Access
3D mechanical characterization of single cells and small organisms using acoustic manipulation and force microscopy
It is currently challenging to mechanically assess 3D specimens without manual handling. Here the authors combine a micro-force sensor and an acoustically controlled manipulation device to enable rotation of samples while assessing mechanical properties at the chosen region.
- Nino F. Läubli
- , Jan T. Burri
- & Bradley J. Nelson
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Article
| Open Access
Lung cancer organoids analyzed on microwell arrays predict drug responses of patients within a week
The lengthy time in establishing patient-derived organoids(PDOs) hampers the implementation of PDO-based drug sensitivity tests in clinics. Here, the authors show a microwell array-based method to predict patient’s responses to anti-cancer therapies in a week using lung cancer organoids.
- Yawei Hu
- , Xizhao Sui
- & Peng Liu
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Article
| Open Access
Automatic synchronisation of the cell cycle in budding yeast through closed-loop feedback control
It is difficult to synchronize the cell cycle in a population of yeast cells for extended periods of time. Here the authors use a cybergenetic system with inbuilt feedback to synchronize a population of modified yeast.
- Giansimone Perrino
- , Sara Napolitano
- & Diego di Bernardo
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Article
| Open Access
Machine learning enables design automation of microfluidic flow-focusing droplet generation
Devices for droplet generation are at the heart of many microfluidic applications but difficult to tailor for specific cases. Lashkaripour et al. show how design customization can greatly be simplified by combining rapid prototyping with data-driven machine learning strategies.
- Ali Lashkaripour
- , Christopher Rodriguez
- & Douglas Densmore
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Article
| Open Access
Digital microfluidic isolation of single cells for -Omics
Multi-Omic approaches are a powerful way for obtaining in-depth understanding of a cell’s state. Here the authors present DISCO, combining digital microfluidics, laser cell lysis, and artificial intelligence-driven image processing to analyze single-cell genomes, transcriptomes and proteomes in a mixed population.
- Julian Lamanna
- , Erica Y. Scott
- & Aaron R. Wheeler
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Article
| Open Access
A combined high-throughput and high-content platform for unified on-chip synthesis, characterization and biological screening
On-chip synthesis and screening has been used to automate drug discovery but on-chip analysis still remains a major limitation. Here, the authors report on a dendrimer-based surface patterning method to create nanodroplet arrays on materials which allow for on-chip high-throughput analysis.
- Maximilian Benz
- , Arndt Asperger
- & Pavel A. Levkin
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Article
| Open Access
Automated microfluidic platform for dynamic and combinatorial drug screening of tumor organoids
The use of organoids in personalized medicine is promising but high throughput platforms are needed. Here the authors develop an automated, high-throughput, microfluidic 3D organoid culture system that allows combinatorial and dynamic drug treatments and real-time analysis of organoids.
- Brooke Schuster
- , Michael Junkin
- & Savaş Tay
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Article
| Open Access
Versatile live-cell activity analysis platform for characterization of neuronal dynamics at single-cell and network level
Current methods of neuronal network imaging cannot be used for continuous, long-term functional recordings. Here, the authors present a dual-mode high-density microelectrode array, which can simultaneously record in full-frame and high-signal-to-noise modes for label-free electrophysiological measurements.
- Xinyue Yuan
- , Manuel Schröter
- & Urs Frey
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Article
| Open Access
Raman image-activated cell sorting
Most current cell sorting methods are based on fluorescence detection with no imaging capability. Here the authors generate and use Raman image-activated cell sorting with a throughput of around 100 events per second, providing molecular images with no need for labeling.
- Nao Nitta
- , Takanori Iino
- & Keisuke Goda
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Article
| Open Access
Sub-nanowatt microfluidic single-cell calorimetry
Calorimetrically measuring the heat of single cells is currently not possible due to the sensitivity of existing calorimeters. Here the authors present on-chip single cell calorimetry, with a sensitivity over ten-fold greater than the current gold-standard.
- Sahngki Hong
- , Edward Dechaumphai
- & Renkun Chen
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Article
| Open Access
Multi-omic single-cell snapshots reveal multiple independent trajectories to drug tolerance in a melanoma cell line
Detailed understanding of how cancer cells transition from a drug sensitive to a tolerant state is lacking. Here, using single cell proteomic and metabolic data the authors uncover that isogenic BRAF mutant melanoma cells can take two distinct paths to become tolerant to BRAF inhibition.
- Yapeng Su
- , Melissa E. Ko
- & James R. Heath
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Article
| Open Access
High-throughput cell and spheroid mechanics in virtual fluidic channels
High-throughput rheological measurements of cells and cell clusters by microfluidics is limited by fixed channel dimensions. Here the authors create virtual fluidic channels inside the cuvette of commercial flow cytometers to dynamically tune channel cross section to enable rheological measurements from cells and cell clusters.
- Muzaffar H. Panhwar
- , Fabian Czerwinski
- & Oliver Otto
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Article
| Open Access
Highly parallel and efficient single cell mRNA sequencing with paired picoliter chambers
Single-cell RNA-seq can reveal accurate and precise cell types and states. Here the authors present an scRNA-seq platform, Paired-seq, which uses differential flow resistance to achieve 95% cell utilisation efficiency for improved cell-free RNA removal and gene detection.
- Mingxia Zhang
- , Yuan Zou
- & Chaoyong Yang
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Article
| Open Access
Ultracompact 3D microfluidics for time-resolved structural biology
There is a need for more robust sample delivery methods for serial crystallography. Here the authors present the design and characterization of ultracompact 3D microfluidic devices that can be printed, which require less sample, have a lower background signal and allow 3D mixing for time resolved experiments.
- Juraj Knoška
- , Luigi Adriano
- & Michael Heymann
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Article
| Open Access
Microengineered human blood–brain barrier platform for understanding nanoparticle transport mechanisms
Developing an in vitro blood-brain-barrier (BBB) model that reproduces the organ’s complex structure and function is an open challenge. Here the authors present a BBB-on-a-chip that includes endothelial cells, pericytes and a 3D astrocytic network which resembles the morphology and function of astrocytes in the BBB in vivo.
- Song Ih Ahn
- , Yoshitaka J. Sei
- & YongTae Kim
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Article
| Open Access
Large scale and integrated platform for digital mass culture of anchorage dependent cells
Large scale culture of adherent cells would benefit from a platform for continuous monitoring and control of cell growth and culture conditions. Here the authors develop an integrated, smart cell culture platform where cells are grown on multiple layers of thin sensors that can be wirelessly integrated across several incubators.
- Kyoung Won Cho
- , Seok Joo Kim
- & Dae-Hyeong Kim
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Article
| Open Access
A tunable dual-input system for on-demand dynamic gene expression regulation
Cellular systems have numerous mechanisms to control gene expression. Here the authors build a Tet-On system with conditional destablising elements to regulate gene expression and protein stability, allowing fine modulation of mESC signalling pathways.
- Elisa Pedone
- , Lorena Postiglione
- & Lucia Marucci
Modeling early pathophysiological phenotypes of diabetic retinopathy in a human inner blood-retinal barrier-on-a-chip