Chip Based Electroanalytical Systems for Cell Analysis

Spégel, Christer; Heiskanen, Arto; Skjolding, Lars Henrik; Emnéus, Jenny

doi:10.1002/elan.200704130

Cited by 68 publications

(39 citation statements)

References 236 publications

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“…31,32 The development of microfabrication techniques has opened possibilities for constructing novel electrodes and electroanalytical systems, giving rise to various technical developments for single cell neurotransmitter detection. 33,34 Measurements at single cell level provide valuable information about the mechanism of exocytosis and effect of drugs. However, the experimental procedures are labour intensive, limiting the available information.…”

Section: 13mentioning

confidence: 99%

A compact multifunctional microfluidic platform for exploring cellular dynamics in real-time using electrochemical detection

et al. 2014

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A compact multifunctional microfluidic platform for exploring cellular dynamics in real-time using electrochemical detection Downscaling of microfluidic cell culture and detection devices for electrochemical monitoring has mostly focused on miniaturization of the microfluidic chips which are often designed for specific applications and therefore lack functional flexibility. We present a compact microfluidic cell culture and electrochemical analysis platform with in-built fluid handling and detection, enabling complete cell based assays comprising on-line electrode cleaning, sterilization, surface functionalization, cell seeding, cultivation and electrochemical real-time monitoring of cellular dynamics. To demonstrate the versatility and multifunctionality of the platform, we explored amperometric monitoring of intracellular redox activity in yeast (Saccharomyces cerevisiae) and detection of exocytotically released dopamine from rat pheochromocytoma cells (PC12). Electrochemical impedance spectroscopy was used in both applications for monitoring cell sedimentation and adhesion as well as proliferation in the case of PC12 cells. The influence of flow rate on the signal amplitude in the detection of redox metabolism as well as the effect of mechanical stimulation on dopamine release were demonstrated using the programmable fluid handling capability. The here presented platform is aimed at applications utilizing cell based assays, ranging from e.g. monitoring of drug effects in pharmacological studies, characterization of neural stem cell differentiation, and screening of genetically modified microorganisms to environmental monitoring.

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Section: 13mentioning

confidence: 99%

A compact multifunctional microfluidic platform for exploring cellular dynamics in real-time using electrochemical detection

et al. 2014

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“…20 However, during recent years, metal electrode systems 10 based on lithographic microsensor technology have gained increasing attention. 21 Aside from suitability for single cell detection, microfabricated metal electrodes have the advantage of facilitating monitoring of dopamine release from populations of adherently growing cells. This approach gives possibility for fast 15 statistically significant screening of cell populations with respect to their dopaminergic properties.…”

Section: -12mentioning

confidence: 99%

Doped overoxidized polypyrrole microelectrodes as sensors for the detection of dopamine released from cell populations

Sasso

Heiskanen

Diazzi

et al. 2013

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A surface modification of interdigitated gold microelectrodes (IDEs) with a doped polypyrrole (PPy) film for detection of dopamine released from populations of differentiated PC12 cells is presented. A thin PPy layer was potentiostatically electropolymerized from an aqueous pyrrole solution onto electrode surfaces. The conducting polymer film was doped during electropolymerization by introducing counter-ions in the monomer solution. Several counter-ions were tested and the resulting electrode modifications were characterized electrochemically to find the optimal dopant that increases sensitivity in dopamine detection. Overoxidation of the PPy films was shown to contribute to a significant enhancement in sensitivity to dopamine. The changes caused by overoxidation in the electrochemical behavior and electrode morphology were investigated using cyclic voltammetry and SEM as well as AFM, respectively. The optimal dopant for dopamine detection was found to be polystyrene sulfonate anion (PSS-). Rat pheochromocytoma (PC12) cells, a suitable model to study exocytotic dopamine release, were differentiated on IDEs functionalized with an overoxidized PSS--doped PPy film. The modified electrodes were used to amperometrically detect dopamine released by populations of cells upon triggering cellular exocytosis with an elevated K+ concentration. A comparison between the generated current on bare gold electrodes and gold electrodes modified with overoxidized doped PPy illustrates the clear advantage of the modification, yielding 2.6-fold signal amplification. The results also illustrate how to use cell population based dopamine exocytosis measurements to obtain biologically significant information that can be relevant in, for instance, the study of neural stem cell differentiation into dopaminergic neurons

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“…To form closed channels, the PDMS is bonded to a separate glass substrate on which thin-film electrodes are first patterned, typically using a lift-off process. The electrodes can be patterned through photolithography followed by either metal etching or liftoff, through stencil or screen printing, or through nanoimprint lithography of a UV curable resist followed by metal liftoff (28). Such chips can be inexpensive to fabricate, and when integrated with electronics and sample delivery, can comprise part of a more portable and lower-cost system compared to conventional flow cytometers.…”

Section: Impedance Analysis As a Label-free And Non-invasive Techniquementioning

confidence: 99%

“…Microfluidic impedance systems have been developed to characterize both adherent cells as well as cells suspended in a flow (28). All of these techniques are constantly improved whereby impedance analysis seems to have the best chance for miniaturized devices and the broadest range of applications.…”

mentioning

confidence: 99%

Microfluidic impedance‐based flow cytometry

Berardino²,

et al. 2010

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Microfabricated flow cytometers can detect, count, and analyze cells or particles using microfluidics and electronics to give impedance-based characterization. Such systems are being developed to provide simple, low-cost, label-free, and portable solutions for cell analysis. Recent work using microfabricated systems has demonstrated the capability to analyze micro-organisms, erythrocytes, leukocytes, and animal and human cell lines. Multifrequency impedance measurements can give multiparametric, high-content data that can be used to distinguish cell types. New combinations of microfluidic sample handling design and microscale flow phenomena have been used to focus and position cells within the channel for improved sensitivity. Robust designs will enable focusing at high flowrates while reducing requirements for control over multiple sample and sheath flows. Although microfluidic impedance-based flow cytometers have not yet or may never reach the extremely high throughput of conventional flow cytometers, the advantages of portability, simplicity, and ability to analyze single cells in small populations are, nevertheless, where chip-based cytometry can make a large impact. ' 2010International Society for Advancement of Cytometry Key terms microfluidics; impedance characterization; label free; single cell analysis; hydrodynamic focusing; sorting MICROFLUIDIC flow cytometers can bring many advantages to the field of flow cytometry (FCM). Compared to typical flow cytometry channel sizes, the miniaturized dimensions permit microfluidic systems to analyze single cells, to identify cellular variability in gene expression, or drug response within a cell population. Chipbased cytometers can have lower size and costs than conventional benchtop instruments, and may be portable. Today, the developmental aim for microfluidic systems is to reach the same sensitivity and capability for multiparametric analyses as delivered by conventional flow cytometers. Many efforts have been made to improve existing devices and to create new miniaturized high-end instruments. Microfluidic chips can incorporate on-chip cell preparation, cell culture, lysis, and modules for optical, electrophoretic, or genomic analysis (1). They are also suitable for analysis of cells in suspension as well as adherent cells.Miniaturized cytometry devices will have high impact in the development of point-of-care devices in developing countries. Accurate CD4 1 T-cell counts are used to monitor human immunodeficiency virus (HIV)-infected patients, and various thresholds of the number of CD4 1 T lymphocytes per ll of whole blood are used to start antiretroviral therapy (2-5). A simple, single-purpose CD4 cell counting device, which does not require standard laboratory equipment or trained laboratory personnel, could help some of the 33 million HIV-infected people worldwide monitor the stage of infection (6)(7)(8). In this application, increased analysis throughput is a secondary concern compared to increased sensitivity and specificity. Portable, miniatu...

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Chip Based Electroanalytical Systems for Cell Analysis

Cited by 68 publications

References 236 publications

A compact multifunctional microfluidic platform for exploring cellular dynamics in real-time using electrochemical detection

A compact multifunctional microfluidic platform for exploring cellular dynamics in real-time using electrochemical detection

Doped overoxidized polypyrrole microelectrodes as sensors for the detection of dopamine released from cell populations

Microfluidic impedance‐based flow cytometry

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