Integrated Micro-Devices for a Lab-in-Organoid Technology Platform: Current Status and Future Perspectives

Abstract

Advancements in stem cell technology together with an improved understanding of in vitro organogenesis have enabled new routes that exploit cell-autonomous self-organization responses of adult stem cells (ASCs) and homogenous pluripotent stem cells (PSCs) to grow complex, three-dimensional (3D), mini-organ like structures on demand, the so-called organoids. Conventional optical and electrical neurophysiological techniques to acquire functional data from brain organoids, however, are not adequate for chronic recordings of neural activity from these model systems, and are not ideal approaches for throughput screenings applied to drug discovery. To overcome these issues, new emerging approaches aim at fusing sensing mechanisms and/or actuating artificial devices within organoids. Here we introduce and develop the concept of the Lab-in-Organoid (LIO) technology for in-tissue sensing and actuation within 3D cell aggregates. This challenging technology grounds on the self-aggregation of brain cells and on integrated bioelectronic micro-scale devices to provide an advanced tool for generating 3D biological brain models with in-tissue artificial functionalities adapted for routine, label-free functional measurements and for assay’s development. We complete previously reported results on the implementation of the integrated self-standing wireless silicon micro-devices with experiments aiming at investigating the impact on neuronal spheroids of sinusoidal electro-magnetic fields as those required for wireless power and data transmission. Finally, we discuss the technology headway and future perspectives.

Organoids, Biocybersecurity, and Cyberbiosecurity—A Light Exploration

“…Numerous breakthroughs were necessary to make much of organoid development and the possibility of integrating them into hybrid systems possible. The core of this can be broken down into sourcing the cells that make up the organoid, sourcing components for and building the material of the matrix in which these organoids develop, and the equipment that allows for their maintenance, observation, and efficient data extraction [1][2][3][4][5][6][7][8][9][10][11][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][36][37][38][39][40][41][42][43]. Examples include advances in 3D culture techniques, directing of stem cell differentiation, development of bioengineering tools and assays, bioprinting, deployment of microfluidic devices, and artificial matrices to emulate tumor environments effectively in the development of tumoroids [1][2][3][4][5][6][7][8][9][1...…”

“…In the future, integrating organoid intelligence in biocomputing might lead to personalized healthcare security options, depending on patient consent and pairing. This is in part due to the customizability and personalization of organoids to patients and the fact that the researchers can tease meaningful data from the performance of organoids that are exposed to a bevy of tests and or otherwise interrogated by equipment with bio-interfaces [35][36][37][38][39][40][41][42][43]. Same-platform computations (in the biological domain) should theoretically support information transfers with minimized entropic loss.…”

Osteochondral organoids: current advances, applications, and upcoming challenges

“…In vivo tissue-engineered grafts show limited capacity to regenerate the damaged tissue due to poor integration with host cartilage and the failure to retain structural integrity after insertion, resulting in reduced mechanical function [ 181 , 182 ]. Moreover, they are not capable of achieving the same complexity of the interfacial tissue size and gradient structure as native organs and lack the crucial directional cues and physical, structural, and mechanical properties [ 183 ].…”

Advancing the interfacing performances of chronically implantable neural probes in the era of CMOS neuroelectronics

“…Wireless circuits for data communication adapted to high channel count probes have been also reported (Crepaldi et al, 2018), and strategies for the wireless powering of neuro-devices that can be implanted and left floating inside the brain, such as the Microbead (Khalifa et al, 2019) or microsystems developed for organoid experimental models (Angotzi et al, 2022) are potential candidates to improve chronic reliability of electrical recordings and are currently under development, e.g., in the Crossbrain EIC project (CrossBrain, 2023).…”