scholarly journals Microfluidics Integration into Low-Noise Multi-Electrode Arrays

Micromachines ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 727
Author(s):  
Mafalda Ribeiro ◽  
Pamela Ali ◽  
Benjamin Metcalfe ◽  
Despina Moschou ◽  
Paulo R. F. Rocha
Keyword(s):  
Continuous Flow ◽  
Electrode Array ◽  
Static Solution ◽  
Microfluidic System ◽  
Low Noise ◽  
Animal Testing ◽  
Electrode Arrays ◽  
Chip Technology ◽  
On Chip

Organ-on-Chip technology is commonly used as a tool to replace animal testing in drug development. Cells or tissues are cultured on a microchip to replicate organ-level functions, where measurements of the electrical activity can be taken to understand how the cell populations react to different drugs. Microfluidic structures are integrated in these devices to replicate more closely an in vivo microenvironment. Research has provided proof of principle that more accurate replications of the microenvironment result in better micro-physiological behaviour, which in turn results in a higher predictive power. This work shows a transition from a no-flow (static) multi-electrode array (MEA) to a continuous-flow (dynamic) MEA, assuring a continuous and homogeneous transfer of an electrolyte solution across the measurement chamber. The process through which the microfluidic system was designed, simulated, and fabricated is described, and electrical characterisation of the whole structure under static solution and a continuous flow rate of 80 µL/min was performed. The latter reveals minimal background disturbance, with a background noise below 30 µVpp for all flow rates and areas. This microfluidic MEA, therefore, opens new avenues for more accurate and long-term recordings in Organ-on-Chip systems.

scholarly journals A mm-Sized Free-Floating Wireless Implantable Opto-Electro Stimulation Device

Micromachines ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 621
Author(s):  
Yaoyao Jia ◽  
Yan Gong ◽  
Arthur Weber ◽  
Wen Li ◽  
Maysam Ghovanloo
Keyword(s):  
Electrical Stimulation ◽  
Large Scale ◽  
Electrode Array ◽  
Cmos Process ◽  
Optical Stimulation ◽  
In Vivo Experiments ◽  
Stimulation Mode ◽  
Shift Keying ◽  
On Chip

Towards a distributed neural interface, consisting of multiple miniaturized implants, for interfacing with large-scale neuronal ensembles over large brain areas, this paper presents a mm-sized free-floating wirelessly-powered implantable opto-electro stimulation (FF-WIOS2) device equipped with 16-ch optical and 4-ch electrical stimulation for reconfigurable neuromodulation. The FF-WIOS2 is wirelessly powered and controlled through a 3-coil inductive link at 60 MHz. The FF-WIOS2 receives stimulation parameters via on-off keying (OOK) while sending its rectified voltage information to an external headstage for closed-loop power control (CLPC) via load-shift-keying (LSK). The FF-WIOS2 system-on-chip (SoC), fabricated in a 0.35-µm standard CMOS process, employs switched-capacitor-based stimulation (SCS) architecture to provide large instantaneous current needed for surpassing the optical stimulation threshold. The SCS charger charges an off-chip capacitor up to 5 V at 37% efficiency. At the onset of stimulation, the capacitor delivers charge with peak current in 1.7–12 mA range to a micro-LED (µLED) array for optical stimulation or 100–700 μA range to a micro-electrode array (MEA) for biphasic electrical stimulation. Active and passive charge balancing circuits are activated in electrical stimulation mode to ensure stimulation safety. In vivo experiments conducted on three anesthetized rats verified the efficacy of the two stimulation mechanisms. The proposed FF-WIOS2 is potentially a reconfigurable tool for performing untethered neuromodulation.

scholarly journals Microfluidic System for Observation of Bacterial Culture and Effects on Biofilm Formation at Microscale

Micromachines ◽  
2019 ◽  
Vol 10 (9) ◽  
pp. 606 ◽  
Author(s):  
Xiao-Yan Zhang ◽  
Kai Sun ◽  
Aliya Abulimiti ◽  
Pian-Pian Xu ◽  
Zhe-Yu Li
Keyword(s):  
Membrane Fouling ◽  
Continuous Flow ◽  
Biofilm Formation ◽  
Natural World ◽  
Microfluidic System ◽  
Fluorescence Labeling ◽  
In Situ Observation ◽  
Time Observation ◽  
On Chip ◽  
Bacteria Culture

Biofilms exist in the natural world and applied to many industries. However, due to the variety of characteristics caused by their complex components, biofilms can also lead to membrane fouling and recurrent infections which pose threats to human health. So, to make the best use of their advantages and avoid their disadvantages, knowing the best time and methods for improving or preventing biofilm formation is important. In situ observation without fluorescence labeling in microscale and according to a time scale is useful to research biofilm and confine its formation. In this study, we developed a microfluidic system for real-time observation of bacteria culture and biofilms development at microscale. We cultured E. coli ATCC 25922 on a chip at continuous flow of the velocity, which could promote bacterial formation. Biofilms formation under the condition of adding amoxicillin at different times is also discussed. In addition, the mixed strains from sludge were also cultured on chip, and possible factors in biofilm formation are discussed. Our results show that a microfluidic device could culture microorganisms in continuous flow and accelerate them to adhere to the surface, thereby promoting biofilm formation. Overall, this platform is a useful tool in research on initial biofilm formation, which can contribute to preventing biofouling and infections.

scholarly journals Graphene-based carbon-layered electrode array technology for neural imaging and optogenetic applications

2014 ◽  
Vol 5 (1) ◽  
Author(s):  
Dong-Wook Park ◽  
Amelia A. Schendel ◽  
Solomon Mikael ◽  
Sarah K. Brodnick ◽  
Thomas J. Richner ◽  
...  
Keyword(s):  
Soft Tissues ◽  
Electrode Array ◽  
Electrode Arrays ◽  
Neural Imaging ◽  
Brain Surface ◽  
Array Technology ◽  
Micro Electrode Arrays ◽  
The Brain

Abstract Neural micro-electrode arrays that are transparent over a broad wavelength spectrum from ultraviolet to infrared could allow for simultaneous electrophysiology and optical imaging, as well as optogenetic modulation of the underlying brain tissue. The long-term biocompatibility and reliability of neural micro-electrodes also require their mechanical flexibility and compliance with soft tissues. Here we present a graphene-based, carbon-layered electrode array (CLEAR) device, which can be implanted on the brain surface in rodents for high-resolution neurophysiological recording. We characterize optical transparency of the device at >90% transmission over the ultraviolet to infrared spectrum and demonstrate its utility through optical interface experiments that use this broad spectrum transparency. These include optogenetic activation of focal cortical areas directly beneath electrodes, in vivo imaging of the cortical vasculature via fluorescence microscopy and 3D optical coherence tomography. This study demonstrates an array of interfacing abilities of the CLEAR device and its utility for neural applications.

scholarly journals Advanced Microengineered Lung Models for Translational Drug Discovery

2018 ◽  
Vol 23 (8) ◽  
pp. 777-789 ◽  
Author(s):  
Brian F. Niemeyer ◽  
Peng Zhao ◽  
Rubin M. Tuder ◽  
Kambez H. Benam
Keyword(s):  
Biomarker Discovery ◽  
Human Lung ◽  
In Vivo Models ◽  
Chip Technology ◽  
Preclinical Drug Development ◽  
Lung Alveolus ◽  
Organ Level ◽  
On Chip

Lung diseases impose a significant socioeconomic burden and are a leading cause of morbidity and mortality worldwide. Moreover, respiratory medicine, unlike several other therapeutic areas, faces a disappointingly low number of new approved therapies. This is partly due to lack of reliable in vitro or in vivo models that can reproduce organ-level complexity and pathophysiological responses of human lung. Here, we examine new opportunities in application of recently emerged organ-on-chip technology to model human lung alveolus and small airway in preclinical drug development and biomarker discovery. We also discuss challenges that need to be addressed in coming years to further enhance the physiological and clinical relevance of these microsystems, enable their increased accessibility, and support their leap into personalized medicine.

scholarly journals Immunotherapy-on-chip Against an Experimental Sepsis Model

2021 ◽  
Author(s):  
Ioanna Zerva ◽  
Katerina Bakela ◽  
Irene Athanassakis
Keyword(s):  
Micrococcus Luteus ◽  
Experimental Sepsis ◽  
Immunostimulatory Activity ◽  
Cd8 Cells ◽  
Arginase 1 ◽  
Chip Technology ◽  
On Chip ◽  
Lps Treatment

Abstract Lipopolysaccharide (LPS) is commonly used in murine sepsis models, which are largely associated with immunosuppression and collapse of the immune system. After adapting the LPS treatment to the needs of locally bred BALB/c mice, the present study explored the protective role of Micrococcus luteus peptidoglycan (PG) pre-activated vaccine-on chip technology in endotoxemia. The established protocol consisted of five daily intraperitoneal injections of 0.2mg/g LPS, allowing longer survival, necessary for a therapeutic treatment application. A novel immunotherapy technology, the so-called vaccine-on-chip consists of a 3-dimentional laser micro-textured silicon (Si)-scaffold loaded with macrophages and activated in vitro with 1μg/ml PG, which has been previously shown to exert a mild immunostimulatory activity upon subcutaneous implantation. The LPS treatment significantly decreased CD4+ and CD8+ cells, while increasing CD11b+, Gr1+, CD25+, Foxp3+ and class II+ cells. These results were accompanied by increased arginase-1 activity in spleen cell lysates and C-reactive protein (CRP), procalcitonin (PCT), IL-6, TNF-a, IL-10 and IL-18 in the serum, while acquiring severe sepsis phenotype as defined by the murine sepsis scoring. The in vivo application of PG pre-activated implant significantly increased the percentage of CD4+ and CD8+ cells, while decreasing the percentage of Gr1+, CD25+, CD11b+, Foxp3+ cells and arginase-1 activity in the spleen of LPS-treated animals, as well as all serum markers tested, allowing survival and rescuing the severity of sepsis phenotype. In conclusion, these results reveal a novel immunotherapy technology based on PG pre-activated micro-texture Si-scaffolds in LPS endotoxemia, supporting thus its potential use in the treatment of septic patients.

Development and Characterization of an Electrocochleography-Guided Robotics-Assisted Cochlear Implant Array Insertion System

2021 ◽  
pp. 019459982110492
Author(s):  
Allan M. Henslee ◽  
Christopher R. Kaufmann ◽  
Matt D. Andrick ◽  
Parker T. Reineke ◽  
Viral D. Tejani ◽  
...  
Keyword(s):  
Cochlear Implant ◽  
Real Time ◽  
Signal To Noise Ratio ◽  
Electrode Array ◽  
High Signal ◽  
Animal Testing ◽  
Signal To Noise ◽  
Noise Ratio ◽  
Hearing Outcomes

Objective Electrocochleography (ECochG) is increasingly being used during cochlear implant (CI) surgery to detect and mitigate insertion-related intracochlear trauma, where a drop in ECochG signal has been shown to correlate with a decline in hearing outcomes. In this study, an ECochG-guided robotics-assisted CI insertion system was developed and characterized that provides controlled and consistent electrode array insertions while monitoring and adapting to real-time ECochG signals. Study Design Experimental research. Setting A research laboratory and animal testing facility. Methods A proof-of-concept benchtop study evaluated the ability of the system to detect simulated ECochG signal changes and robotically adapt the insertion. Additionally, the ECochG-guided insertion system was evaluated in a pilot in vivo sheep study to characterize the signal-to-noise ratio and amplitude of ECochG recordings during robotics-assisted insertions. The system comprises an electrode array insertion drive unit, an extracochlear recording electrode module, and a control console that interfaces with both components and the surgeon. Results The system exhibited a microvolt signal resolution and a response time <100 milliseconds after signal change detection, indicating that the system can detect changes and respond faster than a human. Additionally, animal results demonstrated that the system was capable of recording ECochG signals with a high signal-to-noise ratio and sufficient amplitude. Conclusion An ECochG-guided robotics-assisted CI insertion system can detect real-time drops in ECochG signals during electrode array insertions and immediately alter the insertion motion. The system may provide a surgeon the means to monitor and reduce CI insertion–related trauma beyond manual insertion techniques for improved CI hearing outcomes.

scholarly journals Tumour-on-chip microfluidic platform for assessment of drug pharmacokinetics and treatment response

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Tudor Petreus ◽  
Elaine Cadogan ◽  
Gareth Hughes ◽  
Aaron Smith ◽  
Venkatesh Pilla Reddy ◽  
...  
Keyword(s):  
Animal Studies ◽  
Drug Exposure ◽  
Drug Effects ◽  
Pharmacokinetic Profile ◽  
Microfluidic System ◽  
Drug Dose ◽  
In Vivo Studies ◽  
On Chip

AbstractMicrophysiological in vitro systems are platforms for preclinical evaluation of drug effects and significant advances have been made in recent years. However, existing microfluidic devices are not yet able to deliver compounds to cell models in a way that reproduces the real physiological drug exposure. Here, we introduce a novel tumour-on-chip microfluidic system that mimics the pharmacokinetic profile of compounds on 3D tumour spheroids to evaluate their response to the treatments. We used this platform to test the response of SW620 colorectal cancer spheroids to irinotecan (SN38) alone and in combination with the ATM inhibitor AZD0156, using concentrations mimicking mouse plasma exposure profiles of both agents. We explored spheroid volume and viability as a measure of cancer cells response and changes in mechanistically relevant pharmacodynamic biomarkers (γH2AX, cleaved-caspase 3 and Ki67). We demonstrate here that our microfluidic tumour-on-chip platform can successfully predict the efficacy from in vivo studies and therefore represents an innovative tool to guide drug dose and schedules for optimal efficacy and pharmacodynamic assessment, while reducing the need for animal studies.

scholarly journals High-Efficiency and High-Throughput On-Chip Exchange of the Continuous Phase in Droplet Microfluidic Systems

2017 ◽  
Vol 22 (5) ◽  
pp. 529-535 ◽  
Author(s):  
Minkyu Kim ◽  
Chia Min Leong ◽  
Ming Pan ◽  
Lucas R. Blauch ◽  
Sindy K. Y. Tang
Keyword(s):  
High Throughput ◽  
Continuous Flow ◽  
High Efficiency ◽  
Scale Up ◽  
Continuous Phase ◽  
Microfluidic System ◽  
Droplet Surface ◽  
Generation Process ◽  
Microfluidic Systems ◽  
On Chip

This article describes an integrated platform for the on-chip exchange of the continuous phase in droplet microfluidic systems. The drops used in this work are stabilized by amphiphilic nanoparticles. For some characterizations and applications of these nanoparticle-stabilized drops, including the measurement of adsorption dynamics of nanoparticles to the droplet surface, it is necessary to change the composition of the continuous phase from that used during the droplet generation process. Thus far, no work has reported the exchange of the continuous phase for a large number (>1 million) of drops in a microfluidic system. This article describes the design and characterization of a high-efficiency and high-throughput on-chip exchanger of the continuous phase in a continuous-flow droplet microfluidic system. The efficiency of exchange was higher than 97%. The throughput was greater than 1 million drops/min, and this can be increased further by increasing the number of parallel exchangers used. Because drops are injected into the exchanger in a continuous-flow manner, the method is directly compatible with automation to further increase its reliability and potential scale-up.

scholarly journals Electrophysiological investigation of intact retina with soft printed organic neural interface

2021 ◽  
Author(s):  
Ieva Vebraite-Adereth ◽  
Moshe David-Pur ◽  
David Rand ◽  
Eric Glowacki ◽  
Yael Hanein
Keyword(s):  
Electrical Stimulation ◽  
Ex Vivo ◽  
Electrode Array ◽  
Carbon Electrodes ◽  
Natural Image ◽  
Neural Firing ◽  
Electrode Arrays ◽  
Electrical Recording ◽  
Research Activities

Abstract Objective. Understanding how the retina converts a natural image or an electrically stimulated one into neural firing patterns is the focus of on-going research activities. Ex vivo, the retina can be readily investigated using multi electrode arrays. However, multi electrode array recording and stimulation from an intact retina (in the eye) has been so far insufficient. Approach. In the present study, we report new soft carbon electrode arrays suitable for recording and stimulating neural activity in an intact retina. Screen-printing of carbon ink on 20 µm polyurethane (PU) film was used to realize electrode arrays with electrodes as small as 40 µm in diameter. Passivation was achieved with a holey membrane, realized using laser drilling in a thin (50 µm) PU film. Plasma polymerized EDOT was used to coat the electrode array to improve the electrode specific capacitance. Chick retinas, embryonic stage day 13, both ex-planted and intact inside an enucleated eye, were used. Main results. A novel fabrication process based on printed carbon electrodes was developed and yielded high capacitance electrodes on a soft substrate. Ex vivo electrical recording of retina activity with carbon electrodes is demonstrated. With the addition of organic photo-capacitors, simultaneous photo-electrical stimulation and electrical recording was achieved. Finally, electrical activity recordings from an intact chick retina (inside enucleated eyes) were demonstrated. Both photosensitive retinal ganglion cell responses and spontaneous retina waves were recorded and their features analyzed. Significance. Results of this study demonstrated soft electrode arrays with unique properties, suitable for simultaneous recording and photo-electrical stimulation of the retina at high fidelity. This novel electrode technology opens up new frontiers in the study of neural tissue in vivo.

scholarly journals Recapitulating the Vasculature Using Organ-On-Chip Technology

2020 ◽  
Vol 7 (1) ◽  
pp. 17 ◽  
Author(s):  
Andreas M.A.O. Pollet ◽  
Jaap M.J. den Toonder
Keyword(s):  
Advantages And Disadvantages ◽  
Biological Relevance ◽  
Chip Technology ◽  
Intrinsic Complexity ◽  
On Chip

The development of Vasculature-on-Chip has progressed rapidly over the last decade and recently, a wealth of fabrication possibilities has emerged that can be used for engineering vessels on a chip. All these fabrication methods have their own advantages and disadvantages but, more importantly, the capability of recapitulating the in vivo vasculature differs greatly between them. The first part of this review discusses the biological background of the in vivo vasculature and all the associated processes. We then evaluate the biological relevance of different fabrication methods proposed for Vasculature-on-Chip, we indicate their possibilities and limitations, and we assess which fabrication methods are capable of recapitulating the intrinsic complexity of the vasculature. This review illustrates the complexity involved in developing in vitro vasculature and provides an overview of fabrication methods for Vasculature-on-Chip in relation to the biological relevance of such methods.

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