Special Issue "Cell and Organ on Chip: Challenges and Advances"

A special issue of Biosensors (ISSN 2079-6374).

Deadline for manuscript submissions: closed (30 September 2015).

Special Issue Editor

Dr. Christophe A. Marquette
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Guest Editor
Institut de Chimie et Biochimie Moléculaires et Supramoléculaires Equipe Génie Enzymatique, Membranes Biomimétiques et Assemblages Supramoléculaires (GEMBAS) Université Lyon 1 - CNRS 5246 ICBMS Bâtiment CPE 43, bd du 11 novembre 1918 69622 Villeurbanne, Cedex, France.
Interests: biochip; 3D bioprinting; diagnostic; electrochemistry; microarray; optical devices surface chemistry
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Special Issue Information

Dear Colleagues,

Cell and organ on chip sensing devices are the new generation of cellular biology analytical tools; they are particularly interesting in the field of cellular transduction information, cell-cell interaction studies and in cellulo drug screening.

Achievement of new cell localization and adhesion concepts, advancement of controlled surface chemistries and detection technologies have led the advancement of devices capable of detecting biochemical information from single cell or synthetic organs.

This special issue invites contributions particularly relating to application-oriented cell and organ on chip devices using innovative development techniques. Examples of application areas include, but are not limited to, drug discovery, multiplex cellular event monitoring, microfluidic cell capture, adhesion contrast and cell analysis multiplex systems.

Dr. Christophe A. Marquette
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biosensors is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.


Keywords

  • cell interaction on chip
  • cell in drop handling
  • cell on chip
  • microfluidic cell handling
  • microarray
  • organ on chip
  • single cell analysis

Published Papers (7 papers)

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Research

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Open AccessArticle
Cancer-Cells on Chip for Label-Free Detection of Secreted Molecules
Biosensors 2016, 6(1), 2; https://doi.org/10.3390/bios6010002 - 15 Jan 2016
Cited by 7
Abstract
In the present report, we are making the proof of concept of cell small populations (from 1 to 100 cells) spotting, culture and secretion detection on a gold surface. In order to keep the cells in a hydrated environment during the robotized micropipetting [...] Read more.
In the present report, we are making the proof of concept of cell small populations (from 1 to 100 cells) spotting, culture and secretion detection on a gold surface. In order to keep the cells in a hydrated environment during the robotized micropipetting and to address different cell lines on a single chip, a biocompatible alginate polymer was used. This approach enables the encapsulation of the cell in a very small volume (30 nL), directly on the substrate and permits a precise control of the number of cells in each alginate bead. After 24 h of culture, the adherent cells are ready for surface plasmon resonance imaging (SPRi) experimentation. To enable the detection of secreted proteins, various antibodies are immobilized in an organized manner on a SPRi sensor and permitted the multiplex detection of different proteins secreted by the different cultured cell lines. Evidence of the real-time detection will be presented for Prostate Specific Antigen (PSA) and β-2-microglobulin (B2M) secreted by prostate cancer cells following induction by dihydrotestosterone (DHT). Different kinetics for the two secreted proteins were then demonstrated and precisely determined using the chip. Full article
(This article belongs to the Special Issue Cell and Organ on Chip: Challenges and Advances)
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Open AccessArticle
A Simple Microfluidic Platform for Long-Term Analysis and Continuous Dual-Imaging Detection of T-Cell Secreted IFN-γ and IL-2 on Antibody-Based Biochip
Biosensors 2015, 5(4), 750-767; https://doi.org/10.3390/bios5040750 - 04 Dec 2015
Cited by 6
Abstract
The identification and characterization, at the cellular level, of cytokine productions present a high interest for both fundamental research and clinical studies. However, the majority of techniques currently available (ELISA, ELISpot, flow cytometry, etc.) have several shortcomings including, notably, the assessment of [...] Read more.
The identification and characterization, at the cellular level, of cytokine productions present a high interest for both fundamental research and clinical studies. However, the majority of techniques currently available (ELISA, ELISpot, flow cytometry, etc.) have several shortcomings including, notably, the assessment of several cytokines in relation to individual secreting cells and the monitoring of living cell responses for a long incubation time. In the present work, we describe a system composed of a microfluidic platform coupled with an antibody microarray chip for continuous SPR imaging and immunofluorescence analysis of cytokines (IL-2 and IFN-γ) secreted by T-Lymphocytes, specifically, and stably captured on the biochip under flow upon continued long-term on-chip culture (more than 24 h). Full article
(This article belongs to the Special Issue Cell and Organ on Chip: Challenges and Advances)
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Open AccessArticle
Microfluidic Impedimetric Cell Regeneration Assay to Monitor the Enhanced Cytotoxic Effect of Nanomaterial Perfusion
Biosensors 2015, 5(4), 736-749; https://doi.org/10.3390/bios5040736 - 27 Nov 2015
Cited by 18
Abstract
In the last decade, the application of nanomaterials (NMs) in technical products and biomedicine has become a rapidly increasing market trend. As the safety and efficacy of NMs are of utmost importance, new methods are needed to study the dynamic interactions of NMs [...] Read more.
In the last decade, the application of nanomaterials (NMs) in technical products and biomedicine has become a rapidly increasing market trend. As the safety and efficacy of NMs are of utmost importance, new methods are needed to study the dynamic interactions of NMs at the nano-biointerface. However, evaluation of NMs based on standard and static cell culture end-point detection methods does not provide information on the dynamics of living biological systems, which is crucial for the understanding of physiological responses. To bridge this technological gap, we here present a microfluidic cell culture system containing embedded impedance microsensors to continuously and non-invasively monitor the effects of NMs on adherent cells under varying flow conditions. As a model, the impact of silica NMs on the vitality and regenerative capacity of human lung cells after acute and chronic exposure scenarios was studied over an 18-h period following a four-hour NM treatment. Results of the study demonstrated that the developed system is applicable to reliably analyze the consequences of dynamic NM exposure to physiological cell barriers in both nanotoxicology and nanomedicine. Full article
(This article belongs to the Special Issue Cell and Organ on Chip: Challenges and Advances)
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Open AccessArticle
Design and Characterization of a Sensorized Microfluidic Cell-Culture System with Electro-Thermal Micro-Pumps and Sensors for Cell Adhesion, Oxygen, and pH on a Glass Chip
Biosensors 2015, 5(3), 513-536; https://doi.org/10.3390/bios5030513 - 30 Jul 2015
Cited by 13
Abstract
We combined a multi-sensor glass-chip with a microfluidic channel grid for the characterization of cellular behavior. The grid was imprinted in poly-dimethyl-siloxane. Mouse-embryonal/fetal calvaria fibroblasts (MC3T3-E1) were used as a model system. Thin-film platinum (Pt) sensors for respiration (amperometric oxygen electrode), acidification (potentiometric [...] Read more.
We combined a multi-sensor glass-chip with a microfluidic channel grid for the characterization of cellular behavior. The grid was imprinted in poly-dimethyl-siloxane. Mouse-embryonal/fetal calvaria fibroblasts (MC3T3-E1) were used as a model system. Thin-film platinum (Pt) sensors for respiration (amperometric oxygen electrode), acidification (potentiometric pH electrodes) and cell adhesion (interdigitated-electrodes structures, IDES) allowed us to monitor cell-physiological parameters as well as the cell-spreading behavior. Two on-chip electro-thermal micro-pumps (ETμPs) permitted the induction of medium flow in the system, e.g., for medium mixing and drug delivery. The glass-wafer technology ensured the microscopic observability of the on-chip cell culture. Connecting Pt structures were passivated by a 1.2 μm layer of silicon nitride (Si3N4). Thin Si3N4 layers (20 nm or 60 nm) were used as the sensitive material of the pH electrodes. These electrodes showed a linear behavior in the pH range from 4 to 9, with a sensitivity of up to 39 mV per pH step. The oxygen sensors were circular Pt electrodes with a sensor area of 78.5 μm2. Their sensitivity was 100 pA per 1% oxygen increase in the range from 0% to 21% oxygen (air saturated). Two different IDES geometries with 30- and 50-μm finger spacings showed comparable sensitivities in detecting the proliferation rate of MC3T3 cells. These cells were cultured for 11 days in vitro to test the biocompatibility, microfluidics and electric sensors of our system under standard laboratory conditions. Full article
(This article belongs to the Special Issue Cell and Organ on Chip: Challenges and Advances)
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Open AccessArticle
Two-Dimensional Algal Collection and Assembly by Combining AC-Dielectrophoresis with Fluorescence Detection for Contaminant-Induced Oxidative Stress Sensing
Biosensors 2015, 5(2), 319-336; https://doi.org/10.3390/bios5020319 - 15 Jun 2015
Cited by 13
Abstract
An alternative current (AC) dielectrophoretic lab-on-chip setup was evaluated as a rapid tool of capture and assembly of microalga Chlamydomonas reinhardtii in two-dimensional (2D) close-packed arrays. An electric field of 100 V·cm−1, 100 Hz applied for 30 min was found [...] Read more.
An alternative current (AC) dielectrophoretic lab-on-chip setup was evaluated as a rapid tool of capture and assembly of microalga Chlamydomonas reinhardtii in two-dimensional (2D) close-packed arrays. An electric field of 100 V·cm−1, 100 Hz applied for 30 min was found optimal to collect and assemble the algae into single-layer structures of closely packed cells without inducing cellular oxidative stress. Combined with oxidative stress specific staining and fluorescence microscopy detection, the capability of using the 2D whole-cell assembly on-chip to follow the reactive oxygen species (ROS) production and oxidative stress during short-term exposure to several environmental contaminants, including mercury, methylmercury, copper, copper oxide nanoparticles (CuO-NPs), and diuron was explored. The results showed significant increase of the cellular ROS when C. reinhardtii was exposed to high concentrations of methylmercury, CuO-NPs, and 10−5 M Cu. Overall, this study demonstrates the potential of combining AC-dielectrophoretically assembled two-dimensional algal structures with cell metabolic analysis using fluorescence staining, as a rapid analytical tool for probing the effect of contaminants in highly impacted environment. Full article
(This article belongs to the Special Issue Cell and Organ on Chip: Challenges and Advances)
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Review

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Open AccessReview
High Content Imaging (HCI) on Miniaturized Three-Dimensional (3D) Cell Cultures
Biosensors 2015, 5(4), 768-790; https://doi.org/10.3390/bios5040768 - 14 Dec 2015
Cited by 20
Abstract
High content imaging (HCI) is a multiplexed cell staining assay developed for better understanding of complex biological functions and mechanisms of drug action, and it has become an important tool for toxicity and efficacy screening of drug candidates. Conventional HCI assays have been [...] Read more.
High content imaging (HCI) is a multiplexed cell staining assay developed for better understanding of complex biological functions and mechanisms of drug action, and it has become an important tool for toxicity and efficacy screening of drug candidates. Conventional HCI assays have been carried out on two-dimensional (2D) cell monolayer cultures, which in turn limit predictability of drug toxicity/efficacy in vivo; thus, there has been an urgent need to perform HCI assays on three-dimensional (3D) cell cultures. Although 3D cell cultures better mimic in vivo microenvironments of human tissues and provide an in-depth understanding of the morphological and functional features of tissues, they are also limited by having relatively low throughput and thus are not amenable to high-throughput screening (HTS). One attempt of making 3D cell culture amenable for HTS is to utilize miniaturized cell culture platforms. This review aims to highlight miniaturized 3D cell culture platforms compatible with current HCI technology. Full article
(This article belongs to the Special Issue Cell and Organ on Chip: Challenges and Advances)
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Open AccessReview
Biocompatible Hydrogels for Microarray Cell Printing and Encapsulation
Biosensors 2015, 5(4), 647-663; https://doi.org/10.3390/bios5040647 - 26 Oct 2015
Cited by 21
Abstract
Conventional drug screening processes are a time-consuming and expensive endeavor, but highly rewarding when they are successful. To identify promising lead compounds, millions of compounds are traditionally screened against therapeutic targets on human cells grown on the surface of 96-wells. These two-dimensional (2D) [...] Read more.
Conventional drug screening processes are a time-consuming and expensive endeavor, but highly rewarding when they are successful. To identify promising lead compounds, millions of compounds are traditionally screened against therapeutic targets on human cells grown on the surface of 96-wells. These two-dimensional (2D) cell monolayers are physiologically irrelevant, thus, often providing false-positive or false-negative results, when compared to cells grown in three-dimensional (3D) structures such as hydrogel droplets. However, 3D cell culture systems are not easily amenable to high-throughput screening (HTS), thus inherently low throughput, and requiring relatively large volume for cell-based assays. In addition, it is difficult to control cellular microenvironments and hard to obtain reliable cell images due to focus position and transparency issues. To overcome these problems, miniaturized 3D cell cultures in hydrogels were developed via cell printing techniques where cell spots in hydrogels can be arrayed on the surface of glass slides or plastic chips by microarray spotters and cultured in growth media to form cells encapsulated 3D droplets for various cell-based assays. These approaches can dramatically reduce assay volume, provide accurate control over cellular microenvironments, and allow us to obtain clear 3D cell images for high-content imaging (HCI). In this review, several hydrogels that are compatible to microarray printing robots are discussed for miniaturized 3D cell cultures. Full article
(This article belongs to the Special Issue Cell and Organ on Chip: Challenges and Advances)
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