Cutaneous horn is a conical, circumscribed, dense hyperkeratotic protrusion from skin with epithe... more Cutaneous horn is a conical, circumscribed, dense hyperkeratotic protrusion from skin with epithelial cornification. It is also known by the Latin name ‘Cornu cutaneum’. This rare medical entity resembles animal horn but histological disparity is present between both. They are more commonly present in sun exposed sites or areas that are prone for actinic radiation, burns and hence frequently seen in forearm and upper part of face. Only few cases have been reported with cutaneous horns in unusual sites. Cutaneous horns occurring in oral cavity or perioral regions are extremely rare. The significance of knowing about this dead keratinous cutaneous horn is that it may occur as a part of or in association with a wide range of underlying pathologies, either malignant, premalignant or benign. Majority are due to benign pathologies. We report an unusual presentation of cutaneous horn in left oral commissure of a 45-year-old gentleman which is an extremely rare perioral location for such an...
Volumetric muscle loss (VML) injuries, such as those from high-energy trauma or tumor ablation, o... more Volumetric muscle loss (VML) injuries, such as those from high-energy trauma or tumor ablation, often result in scar tissue formation and permanent loss of skeletomuscular function. Directly after VML injury formation, neutrophils and macrophages arrive at the wound site, releasing cytokines and growth factors to allow proliferation and innervation. Monitoring the wound healing process by spatially mapping key regulatory wound biomarkers, such as nitric oxide (NO), can elucidate the state of the wound and thus inform critical clinical interventions. While single-point NO probes with sufficient performance for short-term measurements have been produced previously, improvements in device sensitivity, stability, and the number of sensing nodes are needed for in vivo applications. Here we leverage novel nanomaterials and their exceptional electrochemical properties to construct three-dimensional fuzzy graphene (3DFG) microelectrode arrays (MEAs) for the multiplexed electrochemical sensi...
The ability to probe and manipulate electrophysiology at the cellular level is crucial for unders... more The ability to probe and manipulate electrophysiology at the cellular level is crucial for understanding cellular communications and enabling new therapeutics for neurological and psychiatric disorders. Nanomaterial-facilitated photothermal stimulation is a non-invasive technique to manipulate cellular electrophysiology with high spatial precision and rapid response time without the need of genetic modifications. Although recently reported Si-, Au-, and C-based nanomaterials are promising candidates for photothermal stimulation of electrically active cells and tissues, they exhibit limited photothermal conversion efficiency in the near-infrared (NIR) window or have complicated synthesis protocols that prevents direct scale-up. Two-dimensional (2D) Ti3C2 MXene is a promising candidate for optical stimulation due to its high NIR absorption and photothermal energy conversion efficiency. Here, we report an approach for optical modulation of neuronal activity using Ti3C2 MXene flakes. Un...
The ability to manipulate the electrophysiology of electrically active cells and tissues has enab... more The ability to manipulate the electrophysiology of electrically active cells and tissues has enabled a deeper understanding of healthy and diseased states. This has primarily been achieved via bioelectronic actuators that interface engineered materials with biological entities. Graphene has gained recent interest as a building-block for bioelectronic actuators due to its advantageous electrochemical properties and biocompatibility. However, functional graphene bioelectronics exhibit a two-dimensional (2D) topology. This leads to inherent performance limitations due to the limited exposed surface-area and poor interactions with interfaced cells and tissues. Ideal geometry of graphene-based actuators needs to leverage the material’s high surface-area-to-volume ratio to facilitate maximum interaction with the electrode. Here we report a breakthrough three-dimensional (3D) topology of graphene: nanowire templated 3D fuzzy graphene (NT-3DFG), for actuation of electrically active cells an...
The ability to manipulate the electrophysiology of electrically active cells and tissues has enab... more The ability to manipulate the electrophysiology of electrically active cells and tissues has enabled a deeper understanding of healthy and diseased tissue states. This has primarily been achieved via input/output (I/O) bioelectronics that interface engineered materials with biological entities. Stable long-term application of conventional I/O bioelectronics advance as materials and processing techniques develop. Recent advancements have facilitated the development of graphene-based I/O bioelectronics with a wide variety of functional characteristics. Engineering the structural, physical, and chemical properties of graphene nanostructures and integration with modern microelectronics have enabled breakthrough high-density electrophysiological investigations. Here, we review recent advancements in 2D and 3D graphene-based I/O bioelectronics and highlight electrophysiological studies facilitated by these emerging platforms. Challenges and present potential breakthroughs that can be addressed via graphene bioelectronics are discussed. We emphasize the need for a multidisciplinary approach across material science, micro-fabrication, and bioengineering to develop the next generation of I/O bioelectronics.
Investigating the effects of nanoparticle phagocytosis on monocyte activation in diabetic hyperte... more Investigating the effects of nanoparticle phagocytosis on monocyte activation in diabetic hypertension Patients suffering from diabetes are at an increased risk of vascular injury due to the chronic inflammation associated with the disease. A common comorbidity of diabetes is hypertension or increased blood pressure, commonly referred to as diabetic hypertension. Monocyte recruitment and activation plays a decisive role during the pathogenesis of diabetic hypertension. As such, monocytes have the potential to be targeted carriers for therapeutic nanoparticles. Monocyte activation status provides information on the intracellular trafficking of nanoparticles during phagocytosis. However, there is little known about the effect of activation on intracellular trafficking of nanoparticles in diabetic hypertensive monocytes. Angiotensin Converting Enzyme 2 (ACE2) dysregulation is common on the surface of monocytes in diabetic hypertensive patients, and there is a lack of studies to understand the role this plays in monocyte phagocytosis and activation. The goal of this research is to develop a monocyte model similar to diabetic hypertension and characterize the impact of a variety of nanoparticles on monocyte activation. To achieve this model monocyte cell lines which mimics ACE 2 dysregulation were created using lentiviral transduction. After completing a phagocytosis assays in which cells are co-cultured with nanoparticles both under stagnate and shear conditions fluorescence microscopy is used to observe changes in nanoparticle uptake. Common markers of monocyte activation are also measured post assay by qPCR. This research will better characterize how nanotherapeutics impact monocyte activation to better inform drug efficacy in diabetic hypertension.
Dopamine (DA) is a monoamine neurotransmitter involved in the modulation of various physiological... more Dopamine (DA) is a monoamine neurotransmitter involved in the modulation of various physiological brain functions, including learning, motivation, reward, and motor functions. The development of a high sensitivity real-time sensor for multi-site detection of DA with high spatial resolution has critical implications for both neuroscience and clinical communities to improve understanding and treatments of neurological and neuropsychiatric disorders. Here, we present high-surface area out-of-plane grown three-dimensional (3D) fuzzy graphene (3DFG) microelectrode arrays (MEAs) for highly selective, sensitive, and stable DA electrochemical sensing. 3DFG microelectrodes present a remarkable sensitivity to DA (2.87 ± 0.25 nA/nM, withLOD of 990±15 pM), the highest reported for nanocarbon MEAs using Fast Scan Cyclic Voltammetry (FSCV). The high surface area of 3DFG allows for miniaturization of electrode down to 2 x 2 μm^2, without compromising the electrochemical performance. Moreover, 3DFG...
Fuzzy graphene and cellular optoporation enable intracellular recordings of cardiac action potent... more Fuzzy graphene and cellular optoporation enable intracellular recordings of cardiac action potentials on microelectrode arrays.
Objective. Three-dimensional (3D) neuronal spheroid culture serves as a powerful model system for... more Objective. Three-dimensional (3D) neuronal spheroid culture serves as a powerful model system for the investigation of neurological disorders and drug discovery. The success of such a model system requires techniques that enable high-resolution functional readout across the entire spheroid. Conventional microelectrode arrays and implantable neural probes cannot monitor the electrophysiology (ephys) activity across the entire native 3D geometry of the cellular construct. Approach. Here, we demonstrate a 3D self-rolled biosensor array (3D-SR-BA) integrated with a 3D cortical spheroid culture for simultaneous in vitro ephys recording, functional Ca2+ imaging, while monitoring the effect of drugs. We have also developed a signal processing pipeline to detect neural firings with high spatiotemporal resolution from the ephys recordings based on established spike sorting methods. Main results. The 3D-SR-BAs cortical spheroid interface provides a stable, high sensitivity recording of neural...
Bioelectronic devices enable fundamental physiological and electrophysiological research, healthc... more Bioelectronic devices enable fundamental physiological and electrophysiological research, healthcare monitoring, and advanced therapeutics. To meet the demanding device requirements imposed by biomedical applications, graphene-based electronics offer a promising alternative to conventional bioelectronic device materials in an all-carbon platform. Continued advancements in graphene nanostructure synthesis and micro-fabrication techniques allow novel device architectures with vastly tunable physiochemical properties. Here, we highlight recent advances in graphene nanostructure-based bioelectronics. We distinguish between various material geometries and discuss their effect on device performance. Furthermore, we emphasize the continued development of fundamental relationships between 3D device geometries and material properties to allow next-generation bioelectronics for biosensing, electrophysiological recordings, and stimulation.
The development of a high sensitivity real-time sensor for multi-site detection of dopamine (DA) ... more The development of a high sensitivity real-time sensor for multi-site detection of dopamine (DA) with high spatial and temporal resolution is of fundamental importance to study the complex spatial and temporal pattern of DA dynamics in the brain, thus improving the understanding and treatments of neurological and neuropsychiatric disorders. In response to this need, here we present high surface area out-of-plane grown three-dimensional (3D) fuzzy graphene (3DFG) microelectrode arrays (MEAs) for highly selective, sensitive, and stable DA electrochemical sensing. 3DFG microelectrodes present a remarkable sensitivity to DA (2.12 ± 0.05 nA/nM, with LOD of 364.44 ± 8.65 pM), the highest reported for nanocarbon MEAs using Fast Scan Cyclic Voltammetry (FSCV). The high surface area of 3DFG allows for miniaturization of electrode down to 2 × 2 μm2, without compromising the electrochemical performance. Moreover, 3DFG MEAs are electrochemically stable under 7.2 million scans of continuous FSCV cycling, present exceptional selectivity over the most common interferents in vitro with minimum fouling by electrochemical byproducts and can discriminate DA and serotonin (5-HT) in response to the injection of their 50:50 mixture. These results highlight the potential of 3DFG MEAs as a promising platform for FSCV based multi-site detection of DA with high sensitivity, selectivity, and spatial resolution.
Conventional graphene electronics fail to leverage the exceptional surface-area-to-volume ratio o... more Conventional graphene electronics fail to leverage the exceptional surface-area-to-volume ratio of graphene due to the challenges imposed by arranging two-dimensional (2D) nanomaterials in three-dimensional (3D) spaces. Recently, a new topology of graphene, nanowire template 3D fuzzy graphene (NT-3DFG), has been developed to overcome this limitation. We provide an overview of the unique physical and chemical properties of NT-3DFG that are a direct consequence of the material structure and describe NT-3DFG’s promising applications in bioelectronics and energy-related research.
International Journal of Medical and Biomedical Studies, 2020
Paraduodenal hernias (PDH) constitute more than half of internal hernias. Both left and right PDH... more Paraduodenal hernias (PDH) constitute more than half of internal hernias. Both left and right PDH occur due to error of rotation of gut and defective fusion of mesocolon and mesentery with posterior parietal peritoneum. Clinical diagnosis of PDH is very difficult because of its varied presentation and nonspecific symptoms. Prompt diagnosis and surgery is imperative to avoid strangulation of bowel which is associated with high mortality. Before the advent of CECT many were discovered during exploratory laparotomy or unrelated abdominal surgery. Now CECT abdomen has become the gold standard for pre-operative diagnosis of PDH. We report two cases of PDH, one on left side and another on right side, diagnosed preoperatively and treated successfully. Keywords: Paraduodenal hernia, Mesocolic hernia, Treitz hernia, Internal hernia
The ability to modulate cellular electrophysiology is a fundamental aspect for investigation of t... more The ability to modulate cellular electrophysiology is a fundamental aspect for investigation of tissue development, maturation and function. Currently, there is a need for remote, non-genetic, light-induced control of cellular activity in native-like state, three-dimensional (3D) tissues such as spheroids and organoids. Here, we report a breakthrough hybrid-nanomaterial for remote, non-genetic photostimulation of both two-dimensional (2D) and 3D neural cellular systems. We combine one-dimensional (1D) nanowires (NWs) and 2D graphene flakes grown out-of-plane for highly controlled photostimulation at subcellular precision with laser energies lower than hundred nanojoules, 1-2 orders of magnitude lower than Au-, C- and Si-based photostimulation. Photostimulation using NW-templated 3D fuzzy graphene (NT-3DFG) is flexible due to its broadband absorption and does not generate cellular stress. Therefore, it serves a novel powerful toolset for studies of cell signaling within and between t...
Proceedings of the National Academy of Sciences, 2020
The ability to modulate cellular electrophysiology is fundamental to the investigation of develop... more The ability to modulate cellular electrophysiology is fundamental to the investigation of development, function, and disease. Currently, there is a need for remote, nongenetic, light-induced control of cellular activity in two-dimensional (2D) and three-dimensional (3D) platforms. Here, we report a breakthrough hybrid nanomaterial for remote, nongenetic, photothermal stimulation of 2D and 3D neural cellular systems. We combine one-dimensional (1D) nanowires (NWs) and 2D graphene flakes grown out-of-plane for highly controlled photothermal stimulation at subcellular precision without the need for genetic modification, with laser energies lower than a hundred nanojoules, one to two orders of magnitude lower than Au-, C-, and Si-based nanomaterials. Photothermal stimulation using NW-templated 3D fuzzy graphene (NT-3DFG) is flexible due to its broadband absorption and does not generate cellular stress. Therefore, it serves as a powerful toolset for studies of cell signaling within and b...
Microelectrode arrays (MEAs) have enabled investigation of cellular networks at sub-millisecond t... more Microelectrode arrays (MEAs) have enabled investigation of cellular networks at sub-millisecond temporal resolution. However, current MEAs are limited by the large electrode footprint since reducing the electrode's geometric area to sub-cellular dimensions leads to a significant increase in impedance thus affecting its recording capabilities. We report a breakthrough ultra-microelectrodes platform by leveraging the outstanding surface-to-volume ratio of nanowire-templated out-of-plane synthesized three-dimensional fuzzy graphene (NT-3DFG). The enormous surface area of NT-3DFG leads to 140-fold reduction in electrode impedance compared to bare Au microelectrodes, thus enabling scaling down the geometric size by 625-fold to ca. 2 µm × 2 µm. The out-of-plane morphology of NT-3DFG leads to a tight seal with the cell membrane thus enabling recording of electrical signals with high signal-to-noise ratio (SNR) of > 6. This work highlights the possibility to push the limits of the conventional MEA technology to enable electrophysiological investigation at sub-cellular level without the need of any surface coatings. This presented approach would greatly impact our basic understanding of signal transduction within a single cell as well as complex cellular assemblies.
Selective two-electron oxygen reduction reaction (ORR) offers a promising route for hydrogen pero... more Selective two-electron oxygen reduction reaction (ORR) offers a promising route for hydrogen peroxide synthesis, and defective sp 2 carbon-based materials are attractive, low-cost electrocatalysts for this process. However, due to a wide range of possible defect structures formed during material synthesis, identification and fabrication of precise active sites remain a challenge. Here, we report a graphene edgebased electrocatalyst for two-electron ORRnanowire-templated three-dimensional fuzzy graphene (NT-3DFG). NT-3DFG exhibits excellent efficiency (onset potential of 0.79 ± 0.01 V versus RHE), selectivity (93 ± 3 % H2O2), and tunable ORR activity as a function of graphene edge site density. Using spectroscopic surface characterization and density functional theory calculations, we find that NT-3DFG edge sites are readily functionalized by carbonyl (C=O) and hydroxyl (C-OH) groups under alkaline ORR conditions. Our calculations indicate that multiple site configurations at both armchair and zigzag edges may achieve a local coordination environment that allows selective, two-electron ORR. We derive a general geometric descriptor based on the local coordination environment that provides activity predictions of graphene surface sites within ~0.1 V of computed values. Herein we combine synthesis, spectroscopy, and simulations to improve active site characterization and accelerate carbon-based electrocatalyst discovery.
The persistent mullerian duct syndrome (PMDS) is a relatively rare form of internal male pseudohe... more The persistent mullerian duct syndrome (PMDS) is a relatively rare form of internal male pseudohermaphroditism. In this type of male pseudohermaphroditism, there is no disturbance of either primary or secondary external masculinization. Consequently, this anomaly is mostly diagnosed incidentally, generally at operation for cryptorchidism or inguinal hernia. Here, we report a case of 30-year-old patient, an otherwise normal male, presenting with mullerian duct derivatives such as uterus, ovary, fallopian tube, and proximal vagina in the sac of left-sided irreducible inguinal hernia with right-sided undescended testes.
Cutaneous horn is a conical, circumscribed, dense hyperkeratotic protrusion from skin with epithe... more Cutaneous horn is a conical, circumscribed, dense hyperkeratotic protrusion from skin with epithelial cornification. It is also known by the Latin name ‘Cornu cutaneum’. This rare medical entity resembles animal horn but histological disparity is present between both. They are more commonly present in sun exposed sites or areas that are prone for actinic radiation, burns and hence frequently seen in forearm and upper part of face. Only few cases have been reported with cutaneous horns in unusual sites. Cutaneous horns occurring in oral cavity or perioral regions are extremely rare. The significance of knowing about this dead keratinous cutaneous horn is that it may occur as a part of or in association with a wide range of underlying pathologies, either malignant, premalignant or benign. Majority are due to benign pathologies. We report an unusual presentation of cutaneous horn in left oral commissure of a 45-year-old gentleman which is an extremely rare perioral location for such an...
Volumetric muscle loss (VML) injuries, such as those from high-energy trauma or tumor ablation, o... more Volumetric muscle loss (VML) injuries, such as those from high-energy trauma or tumor ablation, often result in scar tissue formation and permanent loss of skeletomuscular function. Directly after VML injury formation, neutrophils and macrophages arrive at the wound site, releasing cytokines and growth factors to allow proliferation and innervation. Monitoring the wound healing process by spatially mapping key regulatory wound biomarkers, such as nitric oxide (NO), can elucidate the state of the wound and thus inform critical clinical interventions. While single-point NO probes with sufficient performance for short-term measurements have been produced previously, improvements in device sensitivity, stability, and the number of sensing nodes are needed for in vivo applications. Here we leverage novel nanomaterials and their exceptional electrochemical properties to construct three-dimensional fuzzy graphene (3DFG) microelectrode arrays (MEAs) for the multiplexed electrochemical sensi...
The ability to probe and manipulate electrophysiology at the cellular level is crucial for unders... more The ability to probe and manipulate electrophysiology at the cellular level is crucial for understanding cellular communications and enabling new therapeutics for neurological and psychiatric disorders. Nanomaterial-facilitated photothermal stimulation is a non-invasive technique to manipulate cellular electrophysiology with high spatial precision and rapid response time without the need of genetic modifications. Although recently reported Si-, Au-, and C-based nanomaterials are promising candidates for photothermal stimulation of electrically active cells and tissues, they exhibit limited photothermal conversion efficiency in the near-infrared (NIR) window or have complicated synthesis protocols that prevents direct scale-up. Two-dimensional (2D) Ti3C2 MXene is a promising candidate for optical stimulation due to its high NIR absorption and photothermal energy conversion efficiency. Here, we report an approach for optical modulation of neuronal activity using Ti3C2 MXene flakes. Un...
The ability to manipulate the electrophysiology of electrically active cells and tissues has enab... more The ability to manipulate the electrophysiology of electrically active cells and tissues has enabled a deeper understanding of healthy and diseased states. This has primarily been achieved via bioelectronic actuators that interface engineered materials with biological entities. Graphene has gained recent interest as a building-block for bioelectronic actuators due to its advantageous electrochemical properties and biocompatibility. However, functional graphene bioelectronics exhibit a two-dimensional (2D) topology. This leads to inherent performance limitations due to the limited exposed surface-area and poor interactions with interfaced cells and tissues. Ideal geometry of graphene-based actuators needs to leverage the material’s high surface-area-to-volume ratio to facilitate maximum interaction with the electrode. Here we report a breakthrough three-dimensional (3D) topology of graphene: nanowire templated 3D fuzzy graphene (NT-3DFG), for actuation of electrically active cells an...
The ability to manipulate the electrophysiology of electrically active cells and tissues has enab... more The ability to manipulate the electrophysiology of electrically active cells and tissues has enabled a deeper understanding of healthy and diseased tissue states. This has primarily been achieved via input/output (I/O) bioelectronics that interface engineered materials with biological entities. Stable long-term application of conventional I/O bioelectronics advance as materials and processing techniques develop. Recent advancements have facilitated the development of graphene-based I/O bioelectronics with a wide variety of functional characteristics. Engineering the structural, physical, and chemical properties of graphene nanostructures and integration with modern microelectronics have enabled breakthrough high-density electrophysiological investigations. Here, we review recent advancements in 2D and 3D graphene-based I/O bioelectronics and highlight electrophysiological studies facilitated by these emerging platforms. Challenges and present potential breakthroughs that can be addressed via graphene bioelectronics are discussed. We emphasize the need for a multidisciplinary approach across material science, micro-fabrication, and bioengineering to develop the next generation of I/O bioelectronics.
Investigating the effects of nanoparticle phagocytosis on monocyte activation in diabetic hyperte... more Investigating the effects of nanoparticle phagocytosis on monocyte activation in diabetic hypertension Patients suffering from diabetes are at an increased risk of vascular injury due to the chronic inflammation associated with the disease. A common comorbidity of diabetes is hypertension or increased blood pressure, commonly referred to as diabetic hypertension. Monocyte recruitment and activation plays a decisive role during the pathogenesis of diabetic hypertension. As such, monocytes have the potential to be targeted carriers for therapeutic nanoparticles. Monocyte activation status provides information on the intracellular trafficking of nanoparticles during phagocytosis. However, there is little known about the effect of activation on intracellular trafficking of nanoparticles in diabetic hypertensive monocytes. Angiotensin Converting Enzyme 2 (ACE2) dysregulation is common on the surface of monocytes in diabetic hypertensive patients, and there is a lack of studies to understand the role this plays in monocyte phagocytosis and activation. The goal of this research is to develop a monocyte model similar to diabetic hypertension and characterize the impact of a variety of nanoparticles on monocyte activation. To achieve this model monocyte cell lines which mimics ACE 2 dysregulation were created using lentiviral transduction. After completing a phagocytosis assays in which cells are co-cultured with nanoparticles both under stagnate and shear conditions fluorescence microscopy is used to observe changes in nanoparticle uptake. Common markers of monocyte activation are also measured post assay by qPCR. This research will better characterize how nanotherapeutics impact monocyte activation to better inform drug efficacy in diabetic hypertension.
Dopamine (DA) is a monoamine neurotransmitter involved in the modulation of various physiological... more Dopamine (DA) is a monoamine neurotransmitter involved in the modulation of various physiological brain functions, including learning, motivation, reward, and motor functions. The development of a high sensitivity real-time sensor for multi-site detection of DA with high spatial resolution has critical implications for both neuroscience and clinical communities to improve understanding and treatments of neurological and neuropsychiatric disorders. Here, we present high-surface area out-of-plane grown three-dimensional (3D) fuzzy graphene (3DFG) microelectrode arrays (MEAs) for highly selective, sensitive, and stable DA electrochemical sensing. 3DFG microelectrodes present a remarkable sensitivity to DA (2.87 ± 0.25 nA/nM, withLOD of 990±15 pM), the highest reported for nanocarbon MEAs using Fast Scan Cyclic Voltammetry (FSCV). The high surface area of 3DFG allows for miniaturization of electrode down to 2 x 2 μm^2, without compromising the electrochemical performance. Moreover, 3DFG...
Fuzzy graphene and cellular optoporation enable intracellular recordings of cardiac action potent... more Fuzzy graphene and cellular optoporation enable intracellular recordings of cardiac action potentials on microelectrode arrays.
Objective. Three-dimensional (3D) neuronal spheroid culture serves as a powerful model system for... more Objective. Three-dimensional (3D) neuronal spheroid culture serves as a powerful model system for the investigation of neurological disorders and drug discovery. The success of such a model system requires techniques that enable high-resolution functional readout across the entire spheroid. Conventional microelectrode arrays and implantable neural probes cannot monitor the electrophysiology (ephys) activity across the entire native 3D geometry of the cellular construct. Approach. Here, we demonstrate a 3D self-rolled biosensor array (3D-SR-BA) integrated with a 3D cortical spheroid culture for simultaneous in vitro ephys recording, functional Ca2+ imaging, while monitoring the effect of drugs. We have also developed a signal processing pipeline to detect neural firings with high spatiotemporal resolution from the ephys recordings based on established spike sorting methods. Main results. The 3D-SR-BAs cortical spheroid interface provides a stable, high sensitivity recording of neural...
Bioelectronic devices enable fundamental physiological and electrophysiological research, healthc... more Bioelectronic devices enable fundamental physiological and electrophysiological research, healthcare monitoring, and advanced therapeutics. To meet the demanding device requirements imposed by biomedical applications, graphene-based electronics offer a promising alternative to conventional bioelectronic device materials in an all-carbon platform. Continued advancements in graphene nanostructure synthesis and micro-fabrication techniques allow novel device architectures with vastly tunable physiochemical properties. Here, we highlight recent advances in graphene nanostructure-based bioelectronics. We distinguish between various material geometries and discuss their effect on device performance. Furthermore, we emphasize the continued development of fundamental relationships between 3D device geometries and material properties to allow next-generation bioelectronics for biosensing, electrophysiological recordings, and stimulation.
The development of a high sensitivity real-time sensor for multi-site detection of dopamine (DA) ... more The development of a high sensitivity real-time sensor for multi-site detection of dopamine (DA) with high spatial and temporal resolution is of fundamental importance to study the complex spatial and temporal pattern of DA dynamics in the brain, thus improving the understanding and treatments of neurological and neuropsychiatric disorders. In response to this need, here we present high surface area out-of-plane grown three-dimensional (3D) fuzzy graphene (3DFG) microelectrode arrays (MEAs) for highly selective, sensitive, and stable DA electrochemical sensing. 3DFG microelectrodes present a remarkable sensitivity to DA (2.12 ± 0.05 nA/nM, with LOD of 364.44 ± 8.65 pM), the highest reported for nanocarbon MEAs using Fast Scan Cyclic Voltammetry (FSCV). The high surface area of 3DFG allows for miniaturization of electrode down to 2 × 2 μm2, without compromising the electrochemical performance. Moreover, 3DFG MEAs are electrochemically stable under 7.2 million scans of continuous FSCV cycling, present exceptional selectivity over the most common interferents in vitro with minimum fouling by electrochemical byproducts and can discriminate DA and serotonin (5-HT) in response to the injection of their 50:50 mixture. These results highlight the potential of 3DFG MEAs as a promising platform for FSCV based multi-site detection of DA with high sensitivity, selectivity, and spatial resolution.
Conventional graphene electronics fail to leverage the exceptional surface-area-to-volume ratio o... more Conventional graphene electronics fail to leverage the exceptional surface-area-to-volume ratio of graphene due to the challenges imposed by arranging two-dimensional (2D) nanomaterials in three-dimensional (3D) spaces. Recently, a new topology of graphene, nanowire template 3D fuzzy graphene (NT-3DFG), has been developed to overcome this limitation. We provide an overview of the unique physical and chemical properties of NT-3DFG that are a direct consequence of the material structure and describe NT-3DFG’s promising applications in bioelectronics and energy-related research.
International Journal of Medical and Biomedical Studies, 2020
Paraduodenal hernias (PDH) constitute more than half of internal hernias. Both left and right PDH... more Paraduodenal hernias (PDH) constitute more than half of internal hernias. Both left and right PDH occur due to error of rotation of gut and defective fusion of mesocolon and mesentery with posterior parietal peritoneum. Clinical diagnosis of PDH is very difficult because of its varied presentation and nonspecific symptoms. Prompt diagnosis and surgery is imperative to avoid strangulation of bowel which is associated with high mortality. Before the advent of CECT many were discovered during exploratory laparotomy or unrelated abdominal surgery. Now CECT abdomen has become the gold standard for pre-operative diagnosis of PDH. We report two cases of PDH, one on left side and another on right side, diagnosed preoperatively and treated successfully. Keywords: Paraduodenal hernia, Mesocolic hernia, Treitz hernia, Internal hernia
The ability to modulate cellular electrophysiology is a fundamental aspect for investigation of t... more The ability to modulate cellular electrophysiology is a fundamental aspect for investigation of tissue development, maturation and function. Currently, there is a need for remote, non-genetic, light-induced control of cellular activity in native-like state, three-dimensional (3D) tissues such as spheroids and organoids. Here, we report a breakthrough hybrid-nanomaterial for remote, non-genetic photostimulation of both two-dimensional (2D) and 3D neural cellular systems. We combine one-dimensional (1D) nanowires (NWs) and 2D graphene flakes grown out-of-plane for highly controlled photostimulation at subcellular precision with laser energies lower than hundred nanojoules, 1-2 orders of magnitude lower than Au-, C- and Si-based photostimulation. Photostimulation using NW-templated 3D fuzzy graphene (NT-3DFG) is flexible due to its broadband absorption and does not generate cellular stress. Therefore, it serves a novel powerful toolset for studies of cell signaling within and between t...
Proceedings of the National Academy of Sciences, 2020
The ability to modulate cellular electrophysiology is fundamental to the investigation of develop... more The ability to modulate cellular electrophysiology is fundamental to the investigation of development, function, and disease. Currently, there is a need for remote, nongenetic, light-induced control of cellular activity in two-dimensional (2D) and three-dimensional (3D) platforms. Here, we report a breakthrough hybrid nanomaterial for remote, nongenetic, photothermal stimulation of 2D and 3D neural cellular systems. We combine one-dimensional (1D) nanowires (NWs) and 2D graphene flakes grown out-of-plane for highly controlled photothermal stimulation at subcellular precision without the need for genetic modification, with laser energies lower than a hundred nanojoules, one to two orders of magnitude lower than Au-, C-, and Si-based nanomaterials. Photothermal stimulation using NW-templated 3D fuzzy graphene (NT-3DFG) is flexible due to its broadband absorption and does not generate cellular stress. Therefore, it serves as a powerful toolset for studies of cell signaling within and b...
Microelectrode arrays (MEAs) have enabled investigation of cellular networks at sub-millisecond t... more Microelectrode arrays (MEAs) have enabled investigation of cellular networks at sub-millisecond temporal resolution. However, current MEAs are limited by the large electrode footprint since reducing the electrode's geometric area to sub-cellular dimensions leads to a significant increase in impedance thus affecting its recording capabilities. We report a breakthrough ultra-microelectrodes platform by leveraging the outstanding surface-to-volume ratio of nanowire-templated out-of-plane synthesized three-dimensional fuzzy graphene (NT-3DFG). The enormous surface area of NT-3DFG leads to 140-fold reduction in electrode impedance compared to bare Au microelectrodes, thus enabling scaling down the geometric size by 625-fold to ca. 2 µm × 2 µm. The out-of-plane morphology of NT-3DFG leads to a tight seal with the cell membrane thus enabling recording of electrical signals with high signal-to-noise ratio (SNR) of > 6. This work highlights the possibility to push the limits of the conventional MEA technology to enable electrophysiological investigation at sub-cellular level without the need of any surface coatings. This presented approach would greatly impact our basic understanding of signal transduction within a single cell as well as complex cellular assemblies.
Selective two-electron oxygen reduction reaction (ORR) offers a promising route for hydrogen pero... more Selective two-electron oxygen reduction reaction (ORR) offers a promising route for hydrogen peroxide synthesis, and defective sp 2 carbon-based materials are attractive, low-cost electrocatalysts for this process. However, due to a wide range of possible defect structures formed during material synthesis, identification and fabrication of precise active sites remain a challenge. Here, we report a graphene edgebased electrocatalyst for two-electron ORRnanowire-templated three-dimensional fuzzy graphene (NT-3DFG). NT-3DFG exhibits excellent efficiency (onset potential of 0.79 ± 0.01 V versus RHE), selectivity (93 ± 3 % H2O2), and tunable ORR activity as a function of graphene edge site density. Using spectroscopic surface characterization and density functional theory calculations, we find that NT-3DFG edge sites are readily functionalized by carbonyl (C=O) and hydroxyl (C-OH) groups under alkaline ORR conditions. Our calculations indicate that multiple site configurations at both armchair and zigzag edges may achieve a local coordination environment that allows selective, two-electron ORR. We derive a general geometric descriptor based on the local coordination environment that provides activity predictions of graphene surface sites within ~0.1 V of computed values. Herein we combine synthesis, spectroscopy, and simulations to improve active site characterization and accelerate carbon-based electrocatalyst discovery.
The persistent mullerian duct syndrome (PMDS) is a relatively rare form of internal male pseudohe... more The persistent mullerian duct syndrome (PMDS) is a relatively rare form of internal male pseudohermaphroditism. In this type of male pseudohermaphroditism, there is no disturbance of either primary or secondary external masculinization. Consequently, this anomaly is mostly diagnosed incidentally, generally at operation for cryptorchidism or inguinal hernia. Here, we report a case of 30-year-old patient, an otherwise normal male, presenting with mullerian duct derivatives such as uterus, ovary, fallopian tube, and proximal vagina in the sac of left-sided irreducible inguinal hernia with right-sided undescended testes.
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Papers by Raghav Garg