Stable long-term chronic brain mapping at the single-neuron level

Fu, Tian-Ming; Hong, Guosong; Zhou, Tao; Schuhmann, Thomas G.; Viveros, Robert D.; Lieber, Charles M.

doi:10.1038/nmeth.3969

Cited by 272 publications

(444 citation statements)

References 49 publications

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“…The free-standing mesh electronics were fabricated using standard photolithography (PL) procedures (Materials and Methods and SI Text) as described in detail elsewhere (23,25,26). The mesh electronics (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Mesh electronics were fabricated following procedures reported previously (23,25,26). Key steps in mesh electronics fabrication are described in SI Text.…”

Section: Methodsmentioning

confidence: 99%

“…To address the issues of conventional rigid devices we have introduced a paradigm for implantable multielectrode probes based upon an ultraflexible open mesh structure (23)(24)(25)(26), where the mesh has a unique combination of structural and mechanical features. Specifically, the mesh has all size features comparable to or smaller than neuron soma and bending stiffness values of ∼0.1 nN·m, comparable to a 150-μm-thick brain tissue slice (i.e., the same as the overall implanted open mesh diameter), ∼0.4 nN·m (27,28) and orders of magnitude smaller (more flexible) than conventional probes (14,29,30).…”

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confidence: 99%

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Syringe-injectable mesh electronics integrate seamlessly with minimal chronic immune response in the brain

Zhou

Hong

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Implantation of electrical probes into the brain has been central to both neuroscience research and biomedical applications, although conventional probes induce gliosis in surrounding tissue. We recently reported ultraflexible open mesh electronics implanted into rodent brains by syringe injection that exhibit promising chronic tissue response and recording stability. Here we report time-dependent histology studies of the mesh electronics/brain-tissue interface obtained from sections perpendicular and parallel to probe long axis, as well as studies of conventional flexible thin-film probes. Confocal fluorescence microscopy images of the perpendicular and parallel brain slices containing mesh electronics showed that the distribution of astrocytes, microglia, and neurons became uniform from 2–12 wk, whereas flexible thin-film probes yield a marked accumulation of astrocytes and microglia and decrease of neurons for the same period. Quantitative analyses of 4- and 12-wk data showed that the signals for neurons, axons, astrocytes, and microglia are nearly the same from the mesh electronics surface to the baseline far from the probes, in contrast to flexible polymer probes, which show decreases in neuron and increases in astrocyte and microglia signals. Notably, images of sagittal brain slices containing nearly the entire mesh electronics probe showed that the tissue interface was uniform and neurons and neurofilaments penetrated through the mesh by 3 mo postimplantation. The minimal immune response and seamless interface with brain tissue postimplantation achieved by ultraflexible open mesh electronics probes provide substantial advantages and could enable a wide range of opportunities for in vivo chronic recording and modulation of brain activity in the future.

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Section: Resultsmentioning

confidence: 99%

“…Mesh electronics were fabricated following procedures reported previously (23,25,26). Key steps in mesh electronics fabrication are described in SI Text.…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Syringe-injectable mesh electronics integrate seamlessly with minimal chronic immune response in the brain

Zhou

Hong

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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193

211

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“…In addition, the active aptamer receptor of the modified graphene devices could be regenerated to yield multiuse selective PSA sensing under these physiological conditions. We believe this work represents a critical step toward general application of nanomaterial-based FET sensors in many areas, including in vitro and in vivo real-time chip-based monitoring of disease marker proteins, which could have substantial impact on both fundamental research and health care, as well as integration in free-standing nanoelectronic scaffolds for engineered tissues and in vivo implants (42).…”

Section: Discussionmentioning

confidence: 99%

Specific detection of biomolecules in physiological solutions using graphene transistor biosensors

Gao

Yang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

229

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Nanomaterial-based field-effect transistor (FET) sensors are capable of label-free real-time chemical and biological detection with high sensitivity and spatial resolution, although direct measurements in high-ionic-strength physiological solutions remain challenging due to the Debye screening effect. Recently, we demonstrated a general strategy to overcome this challenge by incorporating a biomoleculepermeable polymer layer on the surface of silicon nanowire FET sensors. The permeable polymer layer can increase the effective screening length immediately adjacent to the device surface and thereby enable real-time detection of biomolecules in high-ionic-strength solutions. Here, we describe studies demonstrating both the generality of this concept and application to specific protein detection using graphene FET sensors. Concentration-dependent measurements made with polyethylene glycol (PEG)-modified graphene devices exhibited real-time reversible detection of prostate specific antigen (PSA) from 1 to 1,000 nM in 100 mM phosphate buffer. In addition, comodification of graphene devices with PEG and DNA aptamers yielded specific irreversible binding and detection of PSA in pH 7.4 1x PBS solutions, whereas control experiments with proteins that do not bind to the aptamer showed smaller reversible signals. In addition, the active aptamer receptor of the modified graphene devices could be regenerated to yield multiuse selective PSA sensing under physiological conditions. The current work presents an important concept toward the application of nanomaterial-based FET sensors for biochemical sensing in physiological environments and thus could lead to powerful tools for basic research and healthcare.field-effect transistor | Debye screening | surface modification | DNA aptamer receptor | polyethylene glycol N anoelectronic biosensors offer broad capabilities for label-free high-sensitivity real-time detection of biological species that are important to both fundamental research and biomedical applications (1-6). In particular, field-effect transistor (FET) biosensors configured from semiconducting nanowires (1, 2), single-walled carbon nanotubes (1, 3, 4), and graphene (1, 5, 6) have been extensively investigated since the first report of real-time protein detection using silicon nanowire devices (7). Subsequent studies have demonstrated highly sensitive and in some cases multiplexed detection of key analytes, including protein disease markers (8-10), nucleic acids (11-13), and viruses (14), as well as detection of protein-protein interactions (8,(15)(16)(17) and enzymatic activity (8).The success achieved with nanomaterial-based FET biosensors has been limited primarily to measurements in relatively low-ionicstrength nonphysiological solutions due to the Debye screening length (18,19). In short, the screening length in physiological solutions, <1 nm, reduces the field produced by charged macromolecules at the FET surface and thus makes real-time label-free detection difficult. The first method reported to overcome this ...

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“…[140][141][142] Approaches such as non-invasive brain imaging can provide long-term monitoring of brain activity, but its low spatial resolution precludes cellular level investigation. 143 Optical imaging techniques can achieve neuron-resolution mapping but are limited in terms of penetration depth. 144 Electrochemical microsensors incorporated with carbon nanomaterials such as CNT yarn can provide high spatial resolution for dynamics studies in deep brain regions.…”

Section: Effect Of Bio-fouling On Carbon Nanomaterials Based Microelecmentioning

confidence: 99%

Development of Electrochemical Microsensors for in vivo Neurotransmitter Detection

Yang

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Everything that happens in our body and all the interactions we have with the outside world are controlled by our brain. Studies of neurotransmitters are critical for a better understanding of how our brain works. Fast-scan cyclic voltammetry (FSCV) is the most popular electrochemical technique for the in vivo detection of electroactive neurotransmitters and neurochemicals with high temporal resolution. To further improve the detection selectivity, sensitivity, and spatial resolution, carbon nanomaterial based microelectrodes are applied to enhance FSCV for the neurotransmitters detection. In this thesis, I introduce and discuss synthesis and fabrication of several novel carbon nanomaterials, the effect of different surface modifications, and their applications for in vivo neurotransmitter detection.Chapter 1 covers the recent advances in carbon nanomaterial based electrochemical sensors for direct neurotransmitter detection. First, strategies are compared to incorporate carbon nanomaterials into electrochemical sensors for neurotransmitter detection. Second, several new applications are highlighted as well as studies to address the remaining challenges for implementation. Chapters 2-5 describe new carbon nanomaterials and surface treatments for enhanced neurotransmitter detection. The direct growth of CNTs on metal wires is introduced in Chapter 2. Chapter 3 and Chapter 4 introduce three surface modification methods, laser treatment, O2 plasma etching, and anti-static gun treatment, to improve sensitivity, selectivity, and bio-fouling properties on CNT yarn microelectrodes. In Chapter 5, three different types of CNT fiber materials, CNT yarn, PEI/CNT fiber, and CA/CNT fiber, are introduced and compared for the detection of neurotransmitters. Surface physical properties and the electrochemical performance to neurotransmitters are characterized in these studies and correlated using Langmuir adsorption isotherm and diffusion profiles. Moreover, in vivo measurements are performed for dopamine at CNT-Nb microelectrodes and laser treated CNT yarn microelectrodes in Chapter 2 and Chapter 3. The effect of bio-fouling on CNT yarn is discussed in Chapter 4. Yang| iiChapter 6 and Chapter 7 introduce two novel electrode fabrication methods based on 3D printing: a 3D printed mold assisted microelectrode fabrication method and a novel 3D printed electrode design for fiber-like materials. The 3D printing technology with low-cost, high efficiency, and customizable design provides a new path to apply our studies on novel fiber-like carbon nanomaterials and surface modifications to broader applications.Overall, this thesis explores the synthesis and fabrication of several novel carbon nanomaterials, the effect of different surface modifications, and their applications for in vivo neurotransmitters detection. Moreover, the electrode surface properties are also characterized and then correlated to their electrochemical performance. The systematic comparison of different carbon nanomaterials and different surface modificati...

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Stable long-term chronic brain mapping at the single-neuron level

Cited by 272 publications

References 49 publications

Syringe-injectable mesh electronics integrate seamlessly with minimal chronic immune response in the brain

Syringe-injectable mesh electronics integrate seamlessly with minimal chronic immune response in the brain

Specific detection of biomolecules in physiological solutions using graphene transistor biosensors

Development of Electrochemical Microsensors for in vivo Neurotransmitter Detection

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