Selective intracellular delivery and intracellular recordings combined in MEA biosensors

Abstract

Biological studies on in vitro cell cultures are of fundamental importance to investigate cells response to external stimuli, such as new drugs for treatment of specific pathologies, or to study communication between electrogenic cells. Although three-dimensional (3D) nanostructures brought tremendous improvements on biosensors used for various biological in vitro studies, including drug delivery and electrical recording, there is still a lack of multifunctional capabilities that could help gaining deeper insights in several bio-related research fields. In this work, the electrical recording of large cell ensembles and the intracellular delivery of few selected cells are combined on the same device by integrating microfluidics channels on the bottom of a multi-electrode array decorated with 3D hollow nanostructures. The novel platform allows to record intracellular-like action potentials from large ensembles of cardiomyocytes derived from human Induced Pluripotent Stem Cells (hiPSC) and from the HL-1 line, while different molecules are selectively delivered into single/few targeted cells. The proposed approach shows high potential for enabling new comprehensive studies that can relate drug effects to network level cell communication processes.

Nanoneedle Platforms: The Many Ways to Pierce the Cell Membrane

“…[ 52 ] Importantly, this technique is distinguished from nanoneedle‐based electrodes that require electroporation to stimulate the cells, which potentially alters the intrinsic activity of cells. Additionally, this optoporation platform combines electrical recording of large numbers of cells and intracellular delivery of appointed cells together on the same device, [ 170 ] by integrating 3D hollow nanostructures with microfluidic systems and a multielectrode setup.…”

Biomaterials-based approaches to model embryogenesis

“…This approach delivers nucleic acids, proteins and peptides intracellularly with the potential to generate complex spatiotemporal patterns of autocrine and paracrine signalling, which could orchestrate signals in stem cells. 119,120,[122][123][124] Furthermore, nanostraws and other nanoconduits 125 can also rapidly sample intracellular fluid with single cell resolution, potentially enabling molecular mapping of complex models of embryogenesis. Alternatively, to electroporation, nanomaterials interacting with light can also induce local permeabilization of the cell membrane, thus enabling spatiotemporally patterned delivery.…”

Microfluidic Multielectrode Arrays for Spatially Localized Drug Delivery and Electrical Recordings of Primary Neuronal Cultures

“…In this regard, further efforts were made in order to develop a functional approach that combines high precision cell response monitoring with a simultaneous molecule delivery. In previous work from our group, exploiting the multifunctional capabilities of hollow 3D nanostructures, we developed a tool able to monitor the bioelectrical activity of electrogenic cells while locally treating them with exogenous molecules (Cerea et al, 2018). Here, the hollow nanoantennas were used as a hybrid structure for intra-and extra-cellular recordings and as a nanoscale tool for selective and intracellular delivery.…”