Fabrication and characterization of microsieve electrode array (<i>µ</i>SEA) enabling cell positioning on 3D electrodes

Schurink, Bart; Tiggelaar, Roald M.; Gardeniers, Han; Lüttge, Regina

doi:10.1088/0960-1317/27/1/015017

Cited by 9 publications

(9 citation statements)

References 46 publications

(51 reference statements)

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“…In this regard, recent advancements in microfabrication techniques have brought micro-sieve array devices wherein the micro-sieves are scaled to the neuron size, enabling hydrodynamic single-cell capture [ 190 , 191 , 192 ] ( Figure 7 B). These devices have also been demonstrated to be suitable for integration of microelectrodes for electrophysiological measurements with single neuron resolution [ 193 ]. More recently, microfluidic MEAs have been developed, which allow simultaneous electrical recording and localized drug delivery [ 194 ] ( Figure 7 C), thanks to which it is possible to address the effect of biochemical modulation of small neuronal ensembles on the overall network activity.…”

Section: Methods For Generating Brain-on-chipmentioning

confidence: 99%

Electrophysiology Read-Out Tools for Brain-on-Chip Biotechnology

et al. 2021

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Brain-on-Chip (BoC) biotechnology is emerging as a promising tool for biomedical and pharmaceutical research applied to the neurosciences. At the convergence between lab-on-chip and cell biology, BoC couples in vitro three-dimensional brain-like systems to an engineered microfluidics platform designed to provide an in vivo-like extrinsic microenvironment with the aim of replicating tissue- or organ-level physiological functions. BoC therefore offers the advantage of an in vitro reproduction of brain structures that is more faithful to the native correlate than what is obtained with conventional cell culture techniques. As brain function ultimately results in the generation of electrical signals, electrophysiology techniques are paramount for studying brain activity in health and disease. However, as BoC is still in its infancy, the availability of combined BoC–electrophysiology platforms is still limited. Here, we summarize the available biological substrates for BoC, starting with a historical perspective. We then describe the available tools enabling BoC electrophysiology studies, detailing their fabrication process and technical features, along with their advantages and limitations. We discuss the current and future applications of BoC electrophysiology, also expanding to complementary approaches. We conclude with an evaluation of the potential translational applications and prospective technology developments.

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Section: Methods For Generating Brain-on-chipmentioning

confidence: 99%

Electrophysiology Read-Out Tools for Brain-on-Chip Biotechnology

et al. 2021

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“…3. However, we noticed that following the trapping of the neurons, the capture efficiency was not reproducible (ranging from 21% to 90%) 13 and most of the neurons did not survive the trapping procedure and therefore were not able to network inbetween the 3D micropores. There were several reasons for the limited applicability of the procedure in the original test setup.…”

Section: A Modified Microsieve Electrode Array (Lsea) Setupmentioning

confidence: 97%

“…2). 1,13,14 The original protocol for trapping single neurons inside the 3D micropores involves the use of syringes and pumps and some additional polydimethylsiloxane (PDMS) parts to provide an active pumping mechanism. The original setup 13 and protocol are shown in Fig.…”

Section: A Modified Microsieve Electrode Array (Lsea) Setupmentioning

confidence: 99%

“…2). 13 This enables an organized positioning of neurons and the formation of a spatially controlled neuronal network inbetween the 3D micropores. In this contribution, we demonstrate a new cell trapping procedure to capture single neurons within the lSEA without the need to use syringes or pumps but by exploiting passive pumping and capillary phenomena.…”

Section: Introductionmentioning

confidence: 99%

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Passive pumping for the parallel trapping of single neurons onto a microsieve electrode array

Frimat

Schurink

Lüttge

2017

Journal of Vacuum Science &Amp; Technology B, Nanotechnology and Microelectronics: Materials, Processing, Measurement, and Phen

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Recent advances in brain-on-a-chip technology have led to the development of modified microelectrode arrays. Previously, the authors have contributed to this exciting field of neuroscience by demonstrating a fabrication process for producing microsieve chips that contain three-dimensional (3D) micropores at the electrodes [termed microsieve electrode arrays (μSEAs)]. This chip allows us to trap hundreds of single neuronal cells in parallel onto the electrodes [B. Schurink and R. Luttge, J. Vac. Sci. Technol., B 31, 06F903 (2013)]. However, trapping the neurons reproducibly under gentle, biocompatible conditions remains a challenge. The current setup involves the use of a hand-operated syringe that is connected to the back of the μSEA chip with a polydimethylsiloxane (PDMS) construct. This makes the capture process rather uncontrolled, which can lead to either cell damage by shear stress or the release of trapped neurons when unplugging the syringe and PDMS constructs. Although, the authors could achieve an efficient capture rate of single neurons within the 3D micropores (80%–90% filling efficiency), cell culture performance varied significantly. In this paper, the authors introduce a passive pumping mechanism for the parallel trapping of neurons onto the μSEA chip with the goal to improve its biological performance. This method uses the capillary pumping between two droplets (a “pumping droplet” on one side of the chip and a “reservoir droplet” on the other side) to create a stable and controllable flow. Due to simplification of the handling procedure, omitting the use of a syringe and additional connections to the μSEA chip, the set-up is compatible with real time microscopy techniques. Hence, the authors could use optical particle tracking to study the trapping process and record particle velocities by video imaging. Analyzing the particle velocities in the passive pumping regime, the authors can confirm a gentle uniform particle flow through the 3D micropores. The authors show that passive pumping particle velocity can be tightly controlled (from 5 to 7.5 to 10.4 μm/s) simply by changing the droplet volume of the pumping droplets from 20, 40, and 60 μl and keeping the reservoir drop constant (10 μl). The authors demonstrate that neuron capturing efficiency and reproducibility as well as neuronal network formation are greatly improved when using this passive pumping approach.

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“…Here, we also contributed by demonstrating improvements on the polymer microfabrication of microsieves [ 30 ]. These devices serve the idea to transform classical planar MEA systems into 3D read-outs but with the same ease as 2D cultures [ 31 ]. In this way, physically engineered microenvironments, i.e., brain-on-chips, can take advantage of many recent advances of handling single cells by microfluidics and integrated single cell targeting analysis techniques integrated in a chip format.…”

mentioning

confidence: 99%