Materials Chemistry of Neural Interface Technologies and Recent Advances in Three-Dimensional Systems.
TL;DR: In this paper, a review summarizes the essential role of chemistry in this field of research, with an emphasis on recently published results and developing trends, including 3D bioelectronic frameworks formed by 3D printing, self-folding and mechanically guided assembly.
Abstract: Advances in materials chemistry and engineering serve as the basis for multifunctional neural interfaces that span length scales from individual neurons to neural networks, neural tissues, and complete neural systems. Such technologies exploit electrical, electrochemical, optical, and/or pharmacological modalities in sensing and neuromodulation for fundamental studies in neuroscience research, with additional potential to serve as routes for monitoring and treating neurodegenerative diseases and for rehabilitating patients. This review summarizes the essential role of chemistry in this field of research, with an emphasis on recently published results and developing trends. The focus is on enabling materials in diverse device constructs, including their latest utilization in 3D bioelectronic frameworks formed by 3D printing, self-folding, and mechanically guided assembly. A concluding section highlights key challenges and future directions.
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TL;DR: In this paper , an ordered assembly strategy is proposed to enable transformation of 2D thin films into 3D structures on diverse curved surfaces, by leveraging predefined mechanical loadings that deform curved elastomer substrates into flat/cylindrical configurations.
Abstract: Electronic devices with engineered three-dimensional (3D) architectures are indispensable for frictional-force sensing, wide-field optical imaging, and flow velocity measurement. Recent advances in mechanically guided assembly established deterministic routes to 3D structures in high-performance materials, through controlled rolling/folding/buckling deformations. The resulting 3D structures are, however, mostly formed on planar substrates and cannot be transferred directly onto another curved substrate. Here, we introduce an ordered assembly strategy to allow transformation of 2D thin films into sophisticated 3D structures on diverse curved surfaces. The strategy leverages predefined mechanical loadings that deform curved elastomer substrates into flat/cylindrical configurations, followed by an additional uniaxial/biaxial prestretch to drive buckling-guided assembly. Release of predefined loadings results in an ordered assembly that can be accurately captured by mechanics modeling, as illustrated by dozens of complex 3D structures assembled on curved substrates. Demonstrated applications include tunable dipole antennas, flow sensors inside a tube, and integrated electronic systems capable of conformal integration with the heart.
17 citations
TL;DR: In this article , a review of the multimodal sensing and stimulation functionalities of recent research is addressed, including photoelectric artifacts, optical image blocking, and light transmission efficiency.
Abstract: Abstract The key to designing an implantable device lies in condensing the synergistic effects of diagnostic and therapeutic methods in a single tool. In conjunction with the integration of electrophysiology and optical modalities, a transparent neural interface alleviates challenges of conventional metal-based microelectrodes. In this review, the multimodal sensing and stimulation functionalities of recent research are addressed. Next, issues that arise when combining functionalities of conventional metal-based, opaque electrode arrays together with optical modalities—(1) photoelectric artifacts, (2) optical image blocking, and (3) light transmission efficiency—are introduced. Then, an introduction of advancing material candidates for transparent neural interfaces follows with the latest research.
13 citations
TL;DR: In this paper , a high-throughput process was developed to fabricate thin, flexible polyimide probes using microelectromechanical-system (MEMS) technologies, where 150 flexible probes were fabricated on each 4 in. Si wafer.
Abstract: Monitoring neurochemical signaling across time scales is critical to understanding how brains encode and store information. Flexible (vs stiff) devices have been shown to improve in vivo monitoring, particularly over longer times, by reducing tissue damage and immunological responses. Here, we report our initial steps toward developing flexible and implantable neuroprobes with aptamer-field-effect transistor (FET) biosensors for neurotransmitter monitoring. A high-throughput process was developed to fabricate thin, flexible polyimide probes using microelectromechanical-system (MEMS) technologies, where 150 flexible probes were fabricated on each 4 in. Si wafer. Probes were 150 μm wide and 7 μm thick with two FETs per tip. The bending stiffness was 1.2 × 10-11 N·m2. Semiconductor thin films (3 nm In2O3) were functionalized with DNA aptamers for target recognition, which produces aptamer conformational rearrangements detected via changes in FET conductance. Flexible aptamer-FET neuroprobes detected serotonin at femtomolar concentrations in high-ionic strength artificial cerebrospinal fluid. A straightforward implantation process was developed, where microfabricated Si carrier devices assisted with implantation such that flexible neuroprobes detected physiological relevant serotonin in a tissue-hydrogel brain mimic.
4 citations
TL;DR: In this paper , the authors developed an adhesive and long-term stable conducting polymer neural interface by a simple two-step electropolymerization methodology, namely, the pre-polymerization of polydopamine (PDA) as an adhesive thin layer followed by electropolasticization of hydroxymethylated 3,4-ethylenedioxythiophene (EDOT-MeOH) with polystyrene sulfonate (PSS) to form stable interpenetrating PEDOTMeOH:PSS/PDA networks.
3 citations
TL;DR: In this article , the recent progress of electronic skin is reviewed, and the technical supports that need to obtain practical electronic skin are also discussed, and electronic skin in terms of short-term, medium-term and long-term applications are introduced.
Abstract: Electronic skin that imitates the characteristics and functions of human skin to sense various external signals and records them as different electrical signals has received extensive attention, and much effort has been made on electronic skin for potential medicine application. However, it still needs a long way to achieve practical applications for electronic skin as consumer electronics, the recent progress of electronic skin is reviewed. First, the crucial characteristics in practical electronic skin are analyzed. Subsequently, the technical supports that need to obtain practical electronic skin are also discussed, and electronic skin in terms of short‐term application, medium‐term application and long‐term application are introduced. Finally, suggestions for future development directions in this fascinating field are put forward.
2 citations
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TL;DR: A family of ultrasensitive protein calcium sensors (GCaMP6) that outperformed other sensors in cultured neurons and in zebrafish, flies and mice in vivo are developed and provide new windows into the organization and dynamics of neural circuits over multiple spatial and temporal scales.
Abstract: Fluorescent calcium sensors are widely used to image neural activity. Using structure-based mutagenesis and neuron-based screening, we developed a family of ultrasensitive protein calcium sensors (GCaMP6) that outperformed other sensors in cultured neurons and in zebrafish, flies and mice in vivo. In layer 2/3 pyramidal neurons of the mouse visual cortex, GCaMP6 reliably detected single action potentials in neuronal somata and orientation-tuned synaptic calcium transients in individual dendritic spines. The orientation tuning of structurally persistent spines was largely stable over timescales of weeks. Orientation tuning averaged across spine populations predicted the tuning of their parent cell. Although the somata of GABAergic neurons showed little orientation tuning, their dendrites included highly tuned dendritic segments (5-40-µm long). GCaMP6 sensors thus provide new windows into the organization and dynamics of neural circuits over multiple spatial and temporal scales.
5,365 citations
Journal Article•
TL;DR: The identification and purification of a cancer stem cell from human brain tumors of different phenotypes that possesses a marked capacity for proliferation, self-renewal, and differentiation is reported.
Abstract: Most current research on human brain tumors is focused on the molecular and cellular analysis of the bulk tumor mass. However, there is overwhelming evidence in some malignancies that the tumor clone is heterogeneous with respect to proliferation and differentiation. In human leukemia, the tumor clone is organized as a hierarchy that originates from rare leukemic stem cells that possess extensive proliferative and self-renewal potential, and are responsible for maintaining the tumor clone. We report here the identification and purification of a cancer stem cell from human brain tumors of different phenotypes that possesses a marked capacity for proliferation, self-renewal, and differentiation. The increased self-renewal capacity of the brain tumor stem cell (BTSC) was highest from the most aggressive clinical samples of medulloblastoma compared with low-grade gliomas. The BTSC was exclusively isolated with the cell fraction expressing the neural stem cell surface marker CD133. These CD133+ cells could differentiate in culture into tumor cells that phenotypically resembled the tumor from the patient. The identification of a BTSC provides a powerful tool to investigate the tumorigenic process in the central nervous system and to develop therapies targeted to the BTSC.
4,899 citations
TL;DR: 3D bioprinting is being applied to regenerative medicine to address the need for tissues and organs suitable for transplantation and developing high-throughput 3D-bioprinted tissue models for research, drug discovery and toxicology.
Abstract: Additive manufacturing, otherwise known as three-dimensional (3D) printing, is driving major innovations in many areas, such as engineering, manufacturing, art, education and medicine. Recent advances have enabled 3D printing of biocompatible materials, cells and supporting components into complex 3D functional living tissues. 3D bioprinting is being applied to regenerative medicine to address the need for tissues and organs suitable for transplantation. Compared with non-biological printing, 3D bioprinting involves additional complexities, such as the choice of materials, cell types, growth and differentiation factors, and technical challenges related to the sensitivities of living cells and the construction of tissues. Addressing these complexities requires the integration of technologies from the fields of engineering, biomaterials science, cell biology, physics and medicine. 3D bioprinting has already been used for the generation and transplantation of several tissues, including multilayered skin, bone, vascular grafts, tracheal splints, heart tissue and cartilaginous structures. Other applications include developing high-throughput 3D-bioprinted tissue models for research, drug discovery and toxicology.
4,841 citations
TL;DR: In this paper, the authors adapted the naturally occurring algal protein Channelrhodopsin-2, a rapidly gated light-sensitive cation channel, by using lentiviral gene delivery in combination with high-speed optical switching to photostimulate mammalian neurons.
Abstract: Temporally precise, noninvasive control of activity in well-defined neuronal populations is a long-sought goal of systems neuroscience. We adapted for this purpose the naturally occurring algal protein Channelrhodopsin-2, a rapidly gated light-sensitive cation channel, by using lentiviral gene delivery in combination with high-speed optical switching to photostimulate mammalian neurons. We demonstrate reliable, millisecond-timescale control of neuronal spiking, as well as control of excitatory and inhibitory synaptic transmission. This technology allows the use of light to alter neural processing at the level of single spikes and synaptic events, yielding a widely applicable tool for neuroscientists and biomedical engineers.
4,411 citations
TL;DR: A human pluripotent stem cell-derived three-dimensional organoid culture system that develops various discrete, although interdependent, brain regions that include a cerebral cortex containing progenitor populations that organize and produce mature cortical neuron subtypes is developed.
Abstract: The complexity of the human brain has made it difficult to study many brain disorders in model organisms, highlighting the need for an in vitro model of human brain development Here we have developed a human pluripotent stem cell-derived three-dimensional organoid culture system, termed cerebral organoids, that develop various discrete, although interdependent, brain regions These include a cerebral cortex containing progenitor populations that organize and produce mature cortical neuron subtypes Furthermore, cerebral organoids are shown to recapitulate features of human cortical development, namely characteristic progenitor zone organization with abundant outer radial glial stem cells Finally, we use RNA interference and patient-specific induced pluripotent stem cells to model microcephaly, a disorder that has been difficult to recapitulate in mice We demonstrate premature neuronal differentiation in patient organoids, a defect that could help to explain the disease phenotype Together, these data show that three-dimensional organoids can recapitulate development and disease even in this most complex human tissue
3,508 citations