Digitalized Human Organoid for Wireless Phenotyping

Kimura, Masaki; Azuma, Momoko; Zhang, Ranran; Thompson, Wendy L.; Mayhew, Christopher N.; Takebe, Takanori

doi:10.1016/j.isci.2018.05.007

Cited by 14 publications

(7 citation statements)

References 22 publications

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“…Another study used commercial radio frequency identification (RFID) chips of 460 × 480 µm 2 in size integrated into reaggregated iPSC-derived endoderm spheroids to demonstrate phenotypic screenings of a pool of RFID-modified organoids. [19] On the other hand, a new class of extracellular tissue-integrated microdevices might be developed by exploiting recent achievements in the massive downscaling of free-floating microelectronic independent biosensor nodes for sub-millisecond neural activity recordings down to 10-100 µm in size. [20] Recently, we proposed a circuit architecture for large-scale radiofrequency (RF) based, low-power active complementary metal-oxide-semiconductor (CMOS) microdevices (100 × 100 × 50 µm 3 ) providing integrated circuits for extracellular sensing of neural activity in organoids.…”

Section: Introductionmentioning

confidence: 99%

Surface‐Functionalized Self‐Standing Microdevices Exhibit Predictive Localization and Seamless Integration in 3D Neural Spheroids

et al. 2020

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diseases and develop potential cures. [1] Developments across the fields of biotechnology, tissue engineering, biomaterials, and microtechnology, have led to in vitro models ranging from multilayer 3D cell cultures [2] to small self-standing cell aggregates called spheroids, [3] up to complex brain organoids derived from human pluripotent stem (hPS) cells. [4] Albeit grown in an artificial in vitro environment, the shift from conventional 2D neural cultures to 3D models was shown to better mimic the complexity of intertwined 3D networks found in the brain. [5] hPS-derived brain organoids can indeed recapitulate several aspects specific to human brain development at the level of gene expression, [6] cell-type differentiation and network formation, [7] and can express phenotypes of human brain diseases when generated from patient-derived hPS-cells. [4a,8] Following these results, 3D neural cell assemblies have raised a large interest for the study of human brain diseases and therapies. Furthermore, these models can overcome certain limitations of currently used animal models, such as low experimental accessibility for functional studies, [9] low sample size, low reproducibility and, above all, poor translational relevance of screening results to humans. [5] The routine experimental use of 3D brain tissue models, however, remains largely unpractical for applications in drugdiscovery. On one side, intermodel variability and unmonitored cellular viability can affect the reliable generation of complex 3D brain tissue model systems. For instance, as 3D models become critically sized, the low diffusion of nutrients and oxygen tends to induce the formation of a necrotic core, [1b,4a,5] with consequent losses in cellular viability. On the other side, available biosensing technologies are not yet adapted for the routine monitoring of biosignals such as neural activity inside individual 3D models. This hinders studies aiming toward a better understanding of the emergence of spontaneous neural activity in these models as well as their optimization to reliably generate electrically active brain tissue models for functional assays. Over the last few years, researchers have been working on protocols for culturing organoids with minimal variability, mainly focusing on homogenizing morphologies. [4c] As far as monitoring brain organoids, current major biosensing Brain organoids is an exciting technology proposed to advance studies on human brain development, diseases, and possible therapies. Establishing and applying such models, however, is hindered by the lack of technologies to chronically monitor neural activity. A promising new approach comprising selfstanding biosensing microdevices capable of achieving seamless tissue integration during cell aggregation and culture. To date, there is little information on how to control the aggregation of such bioartificial 3D neural assemblies. Here, the growth of hybrid neurospheroids obtained by the aggregation of silicon sham microchips (100 × 100 × 50 μm 3) with primary cortical cells ...

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Section: Introductionmentioning

confidence: 99%

Surface‐Functionalized Self‐Standing Microdevices Exhibit Predictive Localization and Seamless Integration in 3D Neural Spheroids

et al. 2020

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“…Thus, a subwavelength RFID design operating at near field is required for the RFID to be implantable inside of cells and for millimeter wavelength RF communication. So far, the most similar and smallest realization of implanted electronic chips has been 400 µ m RFID chips (commercially produced) embedded in organelles 26 . Figure 1 shows a rendering in which individual cells are tagged with the RFID tags.…”

Section: Resultsmentioning

confidence: 99%

Intracellular detection and communication of a wireless chip in cell

Yang

Akin

et al. 2021

Sci Rep

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The rapid growth and development of technology has had significant implications for healthcare, personalized medicine, and our understanding of biology. In this work, we leverage the miniaturization of electronics to realize the first demonstration of wireless detection and communication of an electronic device inside a cell. This is a significant forward step towards a vision of non-invasive, intracellular wireless platforms for single-cell analyses. We demonstrate that a 25 $$\upmu $$ μ m wireless radio frequency identification (RFID) device can not only be taken up by a mammalian cell but can also be detected and specifically identified externally while located intracellularly. The S-parameters and power delivery efficiency of the electronic communication system is quantified before and after immersion in a biological environment; the results show distinct electrical responses for different RFID tags, allowing for classification of cells by examining the electrical output noninvasively. This versatile platform can be adapted for realization of a broad modality of sensors and actuators. This work precedes and facilitates the development of long-term intracellular real-time measurement systems for personalized medicine and furthering our understanding of intrinsic biological behaviors. It helps provide an advanced technique to better assess the long-term evolution of cellular physiology as a result of drug and disease stimuli in a way that is not feasible using current methods.

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“…Optically interfaced self-standing microscopic silicon particle devices have been recently proposed for intracellular readouts [ 294 , 295 ] and demonstrated on isolated cells or 2D cell cultures for cell tracking using a barcode system [ 296 ], intracellular pressure sensing [ 297 ], or to implement multistage delivery systems [ 298 ]. Commercial radio frequency identification (RFID) chips of 460 × 480 µm 2 in size integrated into re-aggregated iPSC-derived endoderm spheroids have been proposed to demonstrate phenotypic screenings of a pool of RFID-modified organoids [ 299 ]. However, these circuits do not yet provide the capability of electrophysiological signals read-out.…”

Section: Brain-on-chip Electrophysiology: Fabrication Features Anmentioning

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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Digitalized Human Organoid for Wireless Phenotyping

Cited by 14 publications

References 22 publications

Surface‐Functionalized Self‐Standing Microdevices Exhibit Predictive Localization and Seamless Integration in 3D Neural Spheroids

Surface‐Functionalized Self‐Standing Microdevices Exhibit Predictive Localization and Seamless Integration in 3D Neural Spheroids

Intracellular detection and communication of a wireless chip in cell

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

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