PMID- 35081486 OWN - NLM STAT- MEDLINE DCOM- 20220222 LR - 20220222 IS - 1873-4235 (Electronic) IS - 0956-5663 (Linking) VI - 202 DP - 2022 Apr 15 TI - Multielectrode biosensor chip for spatial resolution screening of 3D cell models based on microcavity arrays. PG - 114010 LID - S0956-5663(22)00050-1 [pii] LID - 10.1016/j.bios.2022.114010 [doi] AB - Three-dimensional cell models represent the native in vivo situation more closely than two-dimensional cultures and are therefore preferred today for in vitro studies. In this context, there is a great demand for fast, non-invasive, real-time, and label-free methods that are capable for detailed analyses of three-dimensional cultures. To characterize heterogeneous cultures or to detect localized drug effects, a measurement method such as impedance spectroscopy in combination with microcavity arrays (MCAs) is desirable, which additionally offers spatial resolution. To overcome these limitations of the previously described MCA based on opaque silicon substrates and a square shape with four measurement electrodes imposed by the crystal structure, we used the selective laser etching (SLE) method to fabricate microcavities in fused silica and borosilicate glass without geometric constraints. We successfully developed MCAs with variable base including up to eight measurement electrodes in one cavity, which allows the increase in the number of electrode combinations to improve spatial resolution. In addition, we integrated a central cone electrode at the cavity bottom to extend the spatial resolution on the z-axis. To demonstrate the capability of the MCAs, we used MDA-HB-231 spheroids with an enclosed glass sphere to show that the heterogeneity of the model is evident in the relative impedance spectra. Analyses on various cell spheroids highlight the broad applicability of glass MCAs. In conclusion, our SLE-fabricated MCA clearly improve bioelectronic analyses of cellular changes in heterogeneous 3D models. Thus, bioelectronic analysis of electrophysiologically active cells and tumor biopsy samples could significantly benefit from our development. CI - Copyright (c) 2022 Elsevier B.V. All rights reserved. FAU - Zitzmann, Franziska D AU - Zitzmann FD AD - Center for Biotechnology and Biomedicine, Molecular Biological-biochemical Processing Technology, Leipzig University, Deutscher Platz 5, D-04103, Leipzig, Germany. FAU - Schmidt, Sabine AU - Schmidt S AD - Center for Biotechnology and Biomedicine, Molecular Biological-biochemical Processing Technology, Leipzig University, Deutscher Platz 5, D-04103, Leipzig, Germany. FAU - Naumann, Max AU - Naumann M AD - Center for Biotechnology and Biomedicine, Molecular Biological-biochemical Processing Technology, Leipzig University, Deutscher Platz 5, D-04103, Leipzig, Germany. FAU - Belder, Detlev AU - Belder D AD - Institute of Analytical Chemistry, Leipzig University, Linnestrasse 3, 04103, Leipzig, Germany. FAU - Jahnke, Heinz-Georg AU - Jahnke HG AD - Center for Biotechnology and Biomedicine, Molecular Biological-biochemical Processing Technology, Leipzig University, Deutscher Platz 5, D-04103, Leipzig, Germany. Electronic address: heinz-georg.jahnke@bbz.uni-leipzig.de. FAU - Robitzki, Andrea A AU - Robitzki AA AD - Center for Biotechnology and Biomedicine, Molecular Biological-biochemical Processing Technology, Leipzig University, Deutscher Platz 5, D-04103, Leipzig, Germany; Karlsruher Institute of Technology (KIT), Hermann-von-Helmholtz-Platz 1, 76344, Eggenstein-Leopoldshafen, Germany. LA - eng PT - Journal Article DEP - 20220119 PL - England TA - Biosens Bioelectron JT - Biosensors & bioelectronics JID - 9001289 SB - IM MH - *Biosensing Techniques/methods MH - Dielectric Spectroscopy MH - Electric Impedance MH - Electrodes MH - Spheroids, Cellular OTO - NOTNLM OT - 3D cell culture OT - Electrochemical impedance spectroscopy OT - Field potential recording OT - MDA-MB-231 OT - Microcavity array technology OT - Selective laser etching EDAT- 2022/01/27 06:00 MHDA- 2022/02/23 06:00 CRDT- 2022/01/26 20:07 PHST- 2021/10/25 00:00 [received] PHST- 2021/12/24 00:00 [revised] PHST- 2022/01/14 00:00 [accepted] PHST- 2022/01/27 06:00 [pubmed] PHST- 2022/02/23 06:00 [medline] PHST- 2022/01/26 20:07 [entrez] AID - S0956-5663(22)00050-1 [pii] AID - 10.1016/j.bios.2022.114010 [doi] PST - ppublish SO - Biosens Bioelectron. 2022 Apr 15;202:114010. doi: 10.1016/j.bios.2022.114010. Epub 2022 Jan 19.