Label‐Free and Regenerative Electrochemical Microfluidic Biosensors for Continual Monitoring of Cell Secretomes

Shin, Su Ryon; Kilic, Tugba; Zhang, Yu Shrike; Avcı, Hüseyin; Hu, Ning; Kim, Duck Jin; Branco, Cristina; Aleman, Julio; Massa, Solange; Silvestri, Antonia; Kang, Jian; Desalvo, Anna; Hussaini, Mohammed Abdullah; Chae, Su Kyoung; Polini, Alessandro; Bhise, Nupura S.; Hussain, Mohammad Asif; Lee, HeaYeon; Dokmeci, Mehmet R.; Khademhosseini, Ali

doi:10.1002/advs.201600522

Cited by 143 publications

(114 citation statements)

References 65 publications

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“…The microdevices with cell‐laden GelMA hydrogels were cultured in an incubator at 37 °C and 5% CO 2 . Using a WAGO controller and a customized MATLAB program to control solenoid valves, N 2 gas was propelled into the pressure chamber via the gas inlet . Cyclic compressions of 1 Hz were applied to the crosslinked hydrogel within the microdevices for 7 days of culture.…”

Section: Methodsmentioning

confidence: 99%

Cardiac Fibrotic Remodeling on a Chip with Dynamic Mechanical Stimulation

Kong

Lee

Yazdi

et al. 2019

Adv Healthcare Materials

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Cardiac tissue is characterized by being dynamic and contractile, imparting the important role of biomechanical cues in the regulation of normal physiological activity or pathological remodeling. However, the dynamic mechanical tension ability also varies due to extracellular matrix remodeling in fibrosis, accompanied with the phenotypic transition from cardiac fibroblasts (CFs) to myofibroblasts. It is hypothesized that the dynamic mechanical tension ability regulates cardiac phenotypic transition within fibrosis in a strain-mediated manner. In this study, a microdevice that is able to simultaneously and accurately mimic the biomechanical properties of the cardiac physiological and pathological microenvironment is developed. The microdevice can apply cyclic compressions with gradient magnitudes (5-20%) and tunable frequency onto gelatin methacryloyl (GelMA) hydrogels laden with CFs, and also enables the integration of cytokines. The strain-response correlations between mechanical compression and CFs spreading, and proliferation and fibrotic phenotype remolding, are investigated. Results reveal that mechanical compression plays a crucial role in the CFs phenotypic transition, depending on the strain of mechanical load and myofibroblast maturity of CFs encapsulated in GelMA hydrogels. The results provide evidence regarding the strainresponse correlation of mechanical stimulation in CFs phenotypic remodeling, which can be used to develop new preventive or therapeutic strategies for cardiac fibrosis.

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Section: Methodsmentioning

confidence: 99%

Cardiac Fibrotic Remodeling on a Chip with Dynamic Mechanical Stimulation

Kong

Lee

Yazdi

et al. 2019

Adv Healthcare Materials

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“…In recent years, microfluidics‐based electrochemical biosensors have been favored by researchers. Many microfluidics‐based electrochemical sensors have successfully demonstrated that they have great potential for biomarker detection . These detection chips for various antibody proteins have great potential for detection of exosomes.…”

Section: Detection Techniques For Exosomesmentioning

confidence: 99%

Progress in Microfluidics‐Based Exosome Separation and Detection Technologies for Diagnostic Applications

Lin

Chen

et al. 2019

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Exosomes are secreted by most cell types and circulate in body fluids. Recent studies have revealed that exosomes play a significant role in intercellular communication and are closely associated with the pathogenesis of disease. Therefore, exosomes are considered promising biomarkers for disease diagnosis. However, exosomes are always mixed with other components of body fluids. Consequently, separation methods for exosomes that allow high‐purity and high‐throughput separation with a high recovery rate and detection techniques for exosomes that are rapid, highly sensitive, highly specific, and have a low detection limit are indispensable for diagnostic applications. For decades, many exosome separation and detection techniques have been developed to achieve the aforementioned goals. However, in most cases, these two techniques are performed separately, which increases operation complexity, time consumption, and cost. The emergence of microfluidics offers a promising way to integrate exosome separation and detection functions into a single chip. Herein, an overview of conventional and microfluidics‐based techniques for exosome separation and detection is presented. Moreover, the advantages and drawbacks of these techniques are compared.

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“…Indeed, a new trend in the field of organson-chips and in vitro tissue models is to harness the potential offered by the integration of sensing units with the culture chambers to continuously monitor the system. [17][18][19] The present work falls in this area as we have developed a strategy for a sensing device for stem cell differentiation monitoring, with the potential to be integrated within a cell culture chamber. Our technology is based on the coupling of the electrochemical properties of poly (3,4ethylenedioxythiophene): polystyrene sulfonate (PEDOT:PSS), and the specificity brought by monoclonal antibodies targeting the analyte of choice.…”

Section: Introductionmentioning

confidence: 99%

BMP-2 functionalized PEDOT:PSS-based OECTs for stem cell osteogenic differentiation monitoring

Decataldo

Druet

Pappa

et al. 2019

Flex. Print. Electron.

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Stem cell osteogenic differentiation is a complex process, associated with a number of events such as the secretion of collagen type I, osteopontin, osteonectin, osteocalcin and Bone Morphogenic Protein 2 (BMP-2). These molecules can be used as markers to monitor stem cell fate while studying the effects of a specific osteogenic differentiation treatment (e.g. electrical stimulation). Currently available techniques, such as the evaluation of the expression levels of specific genes and end-point biochemical assays, do not allow real-time monitoring of cellular processes, therefore overlooking potentially interesting information. This study explores a promising functionalization strategy towards on-line electrical monitoring of stem cell osteogenic differentiation process, using an organic electrochemical transistor (OECT) to detect cytokines of interest, secreted by cells during the osteogenic differentiation process, such as BMP-2. In this work, antibodies against BMP-2 were anchored on the poly(3,4-ethylenedioxythiophene):polystyrene (PEDOT:PSS) sulfonate gate electrode of an OECT. The biofunctionalization process was evaluated using multiple techniques such as Atomic Force Microscopy, Electrochemical Raman Spectroscopy, Quartz crystal microbalance. Electrode properties were assessed by running chronoamperometric studies, as well as by characterizing the PEDOT:PSS thin film resistance to ion flow by electrochemical impedance spectroscopy and OECT performance using transient (AC) measurements. Finally, a proof-of-concept, biosensor measurement was performed to test our functionalization strategy for sensing, proving that the antibody-functionalized OECTs were able to detect recombinant BMP-2 at levels that are comparable to those used for in vitro stimulation of bone regeneration via soluble osteoinductive factors.

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Label‐Free and Regenerative Electrochemical Microfluidic Biosensors for Continual Monitoring of Cell Secretomes

Cited by 143 publications

References 65 publications

Cardiac Fibrotic Remodeling on a Chip with Dynamic Mechanical Stimulation

Cardiac Fibrotic Remodeling on a Chip with Dynamic Mechanical Stimulation

Progress in Microfluidics‐Based Exosome Separation and Detection Technologies for Diagnostic Applications

BMP-2 functionalized PEDOT:PSS-based OECTs for stem cell osteogenic differentiation monitoring

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