Barrier-on-a-Chip with a Modular Architecture and Integrated Sensors for Real-Time Measurement of Biological Barrier Function

Biological barriers are essential for the maintenance of organ homeostasis and their dysfunction is responsible for many prevalent diseases. Advanced in vitro models of biological barriers have been developed through the combination of 3D cell culture techniques and organ-on-chip (OoC) technology. However, real-time monitoring of tissue function inside the OoC devices has been challenging, with most approaches relying on off-chip analysis and imaging techniques. In this study, we designed and fabricated a low-cost barrier-on-chip (BoC) device with integrated electrodes for the development and real-time monitoring of biological barriers. The integrated electrodes were used to measure transepithelial electrical resistance (TEER) during tissue culture, thereby quantitatively evaluating tissue barrier function. A finite element analysis was performed to study the sensitivity of the integrated electrodes and to compare them with conventional systems. As proof-of-concept, a full-thickness human skin model (FTSm) was grown on the developed BoC, and TEER was measured on-chip during the culture. After 14 days of culture, the barrier tissue was challenged with a benchmark irritant and its impact was evaluated on-chip through TEER measurements. The developed BoC with an integrated sensing capability represents a promising tool for real-time assessment of barrier function in the context of drug testing and disease modelling.

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Integrating Biosensors in Organs-on-Chip Devices: A Perspective on Current Strategies to Monitor Microphysiological Systems

Biosensors ◽

10.3390/bios10090110 ◽

2020 ◽

Vol 10 (9) ◽

pp. 110 ◽

Cited By ~ 2

Author(s):

Erika Ferrari ◽

Cecilia Palma ◽

Simone Vesentini ◽

Paola Occhetta ◽

Marco Rasponi

Keyword(s):

Imaging Techniques ◽

Biological Models ◽

Electromechanical Properties ◽

Human Organs ◽

Tissue Constructs ◽

Microphysiological Systems ◽

Metabolic Activities ◽

On Chip ◽

Chip Analysis

Organs-on-chip (OoC), often referred to as microphysiological systems (MPS), are advanced in vitro tools able to replicate essential functions of human organs. Owing to their unprecedented ability to recapitulate key features of the native cellular environments, they represent promising tools for tissue engineering and drug screening applications. The achievement of proper functionalities within OoC is crucial; to this purpose, several parameters (e.g., chemical, physical) need to be assessed. Currently, most approaches rely on off-chip analysis and imaging techniques. However, the urgent demand for continuous, noninvasive, and real-time monitoring of tissue constructs requires the direct integration of biosensors. In this review, we focus on recent strategies to miniaturize and embed biosensing systems into organs-on-chip platforms. Biosensors for monitoring biological models with metabolic activities, models with tissue barrier functions, as well as models with electromechanical properties will be described and critically evaluated. In addition, multisensor integration within multiorgan platforms will be further reviewed and discussed.

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Real time monitoring of peptide delivery in vitro using high payload pH responsive nanogels

Polymer Chemistry ◽

10.1039/c9py01120j ◽

2020 ◽

Vol 11 (2) ◽

pp. 425-432 ◽

Cited By ~ 2

Author(s):

Shegufta Farazi ◽

Fan Chen ◽

Henry Foster ◽

Raelene Boquiren ◽

Shelli R. McAlpine ◽

...

Keyword(s):

Real Time ◽

Intracellular Delivery ◽

Peptide Delivery ◽

High Loading ◽

Loading Capacity ◽

Ph Responsive ◽

Real Time Monitoring ◽

High Payload

A pH responsive pMAA nanogel that demonstrates high loading capacity and rapid intracellular delivery of hydrophilic peptides.

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Facile solvothermal synthesis of ultrathin spinel ZnMn2O4 nanospheres: An efficient electrocatalyst for in vivo and in vitro real time monitoring of H2O2

Journal of Electroanalytical Chemistry ◽

10.1016/j.jelechem.2021.115674 ◽

2021 ◽

Vol 900 ◽

pp. 115674

Author(s):

Muthaiah Annalakshmi ◽

Sakthivel Kumaravel ◽

T.S.T. Balamurugan ◽

Shen-Ming Chen ◽

Ju-Liang He

Keyword(s):

Real Time ◽

Solvothermal Synthesis ◽

Real Time Monitoring

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Non-invasive, real-time reporting drug release in vitro and in vivo

Chemical Communications ◽

10.1039/c4cc09920f ◽

2015 ◽

Vol 51 (32) ◽

pp. 6948-6951 ◽

Cited By ~ 31

Author(s):

Yanfeng Zhang ◽

Qian Yin ◽

Jonathan Yen ◽

Joanne Li ◽

Hanze Ying ◽

...

Keyword(s):

Drug Release ◽

Real Time ◽

Near Infrared ◽

Reporting System ◽

Real Time Monitoring ◽

Near Infrared Fluorescence ◽

Non Invasive ◽

Fluorescence Dye

Anin vitroandin vivodrug-reporting system is developed for real-time monitoring of drug release via the analysis of the concurrently released near-infrared fluorescence dye.

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NIR-Responsive Lysosomotropic Phototrigger: ʽAIE + ESIPTʼ Active Naphthalene Based Single Component Photoresponsive Nanocarrier with Two-Photon Uncaging and Real-Time Monitoring Ability

10.33774/chemrxiv-2021-nftrb ◽

2021 ◽

Author(s):

Biswajit Roy ◽

Rakesh Mengji ◽

Samrat Roy ◽

Bipul Pal ◽

Avijit Jana ◽

...

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Real Time ◽

Near Infrared ◽

Single Component ◽

Photon Absorption ◽

Real Time Monitoring ◽

Two Photon ◽

Nir Light

In recent times, organelle-targeted drug delivery systems gained tremendous attention due to the site specific delivery of active drug molecules resulting in enhanced bioefficacy. In this context, the phototriggered drug delivery system (DDS) for releasing an active molecule is superior as it provides spatial and temporal control over the release. So far, near infrared (NIR) light responsive organelle targeted DDS has not yet been developed. Hence, we introduced a two-photon NIR-light responsive lysosome targeted ʽAIE + ESIPTʼ active single component DDS based on naphthalene chromophore. The Two-photon absorption cross-section of our DDS is 142 GM at 850 nm. The DDS was converted into pure organic nanoparticles for biological applications. Our nano-DDS is capable of selective targeting, AIE-luminogenic imaging, and drug release within the lysosome. In vitro studies using cancerous cell lines showed that our single component photoresponsive nanocarrier exhibited enhanced cytotoxicity and real-time monitoring ability of the drug release.

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Gold Nanoparticle-Based Fluorescent Theranostics for Real-Time Image-Guided Assessment of DNA Damage and Repair

International Journal of Molecular Sciences ◽

10.3390/ijms20030471 ◽

2019 ◽

Vol 20 (3) ◽

pp. 471 ◽

Cited By ~ 2

Author(s):

Shriya S. Srinivasan ◽

Rajesh Seenivasan ◽

Allison Condie ◽

Stanton L. Gerson ◽

Yanming Wang ◽

...

Keyword(s):

Molecular Imaging ◽

Real Time ◽

Targeted Delivery ◽

Specific Binding ◽

Imaging Techniques ◽

Cancer Cell Line ◽

Molecular Probe ◽

Biodistribution Studies

Chemotherapeutic dosing, is largely based on the tolerance levels of toxicity today. Molecular imaging strategies can be leveraged to quantify DNA cytotoxicity and thereby serve as a theranostic tool to improve the efficacy of treatments. Methoxyamine-modified cyanine-7 (Cy7MX) is a molecular probe which binds to apurinic/apyrimidinic (AP)-sites, inhibiting DNA-repair mechanisms implicated by cytotoxic chemotherapies. Herein, we loaded (Cy7MX) onto polyethylene glycol-coated gold nanoparticles (AuNP) to selectively and stably deliver the molecular probe intravenously to tumors. We optimized the properties of Cy7MX-loaded AuNPs using optical spectroscopy and tested the delivery mechanism and binding affinity using the DLD1 colon cancer cell line in vitro. A 10:1 ratio of Cy7MX-AuNPs demonstrated a strong AP site-specific binding and the cumulative release profile demonstrated 97% release within 12 min from a polar to a nonpolar environment. We further demonstrated targeted delivery using imaging and biodistribution studies in vivo in an xenografted mouse model. This work lays a foundation for the development of real-time molecular imaging techniques that are poised to yield quantitative measures of the efficacy and temporal profile of cytotoxic chemotherapies.

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Real-Time Monitoring Of Intracellular Redox Changes In Human Bronchial Epithelial Cells Undergoing In Vitro Exposure To Ozone

10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a4644 ◽

2012 ◽

Author(s):

Eugene A. Gibbs-Flournoy ◽

Wan-Yun Cheng ◽

Philip A. Bromberg ◽

James M. Samet

Keyword(s):

Epithelial Cells ◽

Real Time ◽

Bronchial Epithelial Cells ◽

Real Time Monitoring ◽

Human Bronchial Epithelial Cells ◽

Bronchial Epithelial ◽

In Vitro Exposure ◽

Intracellular Redox

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An Implantable Inductive Near-Field Communication System with 64 Channels for Acquisition of Gastrointestinal Bioelectrical Activity

Sensors ◽

10.3390/s19122810 ◽

2019 ◽

Vol 19 (12) ◽

pp. 2810 ◽

Cited By ~ 10

Author(s):

Amir Javan-Khoshkholgh ◽

Aydin Farajidavar

Keyword(s):

Real Time ◽

Radio Frequency Identification ◽

Communication System ◽

Near Field ◽

Data Communication ◽

Near Field Communication ◽

Bioelectrical Activity ◽

Real Time Monitoring ◽

Rf Transceiver

High-resolution (HR) mapping of the gastrointestinal (GI) bioelectrical activity is an emerging method to define the GI dysrhythmias such as gastroparesis and functional dyspepsia. Currently, there is no solution available to conduct HR mapping in long-term studies. We have developed an implantable 64-channel closed-loop near-field communication system for real-time monitoring of gastric electrical activity. The system is composed of an implantable unit (IU), a wearable unit (WU), and a stationary unit (SU) connected to a computer. Simultaneous data telemetry and power transfer between the IU and WU is carried out through a radio-frequency identification (RFID) link operating at 13.56 MHz. Data at the IU are encoded according to a self-clocking differential pulse position algorithm, and load shift keying modulated with only 6.25% duty cycle to be back scattered to the WU over the inductive path. The retrieved data at the WU are then either transmitted to the SU for real-time monitoring through an ISM-band RF transceiver or stored locally on a micro SD memory card. The measurement results demonstrated successful data communication at the rate of 125 kb/s when the distance between the IU and WU is less than 5 cm. The signals recorded in vitro at IU and received by SU were verified by a graphical user interface.

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