Hye Rim Cho

Stretchable silicon nanoribbon electronics for skin prosthesis

Sensory receptors in human skin transmit a wealth of tactile and thermal signals from external environments to the brain. Despite advances in our understanding of mechano- and thermosensation, replication of these unique sensory characteristics in artificial skin and prosthetics remains challenging. Recent efforts to develop smart prosthetics, which exploit rigid and/or semi-flexible pressure, strain and temperature sensors, provide promising routes for sensor-laden bionic systems, but with limited stretchability, detection range and spatio-temporal resolution. Here we demonstrate smart prosthetic skin instrumented with ultrathin, single crystalline silicon nanoribbon strain, pressure and temperature sensor arrays as well as associated humidity sensors, electroresistive heaters and stretchable multi-electrode arrays for nerve stimulation. This collection of stretchable sensors and actuators facilitate highly localized mechanical and thermal skin-like perception in response to external stimuli, thus providing unique opportunities for emerging classes of prostheses and peripheral nervous system interface technologies.

A graphene-based electrochemical device with thermoresponsive microneedles for diabetes monitoring and therapy

Owing to its high carrier mobility, conductivity, flexibility and optical transparency, graphene is a versatile material in micro- and macroelectronics. However, the low density of electrochemically active defects in graphene synthesized by chemical vapour deposition limits its application in biosensing. Here, we show that graphene doped with gold and combined with a gold mesh has improved electrochemical activity over bare graphene, sufficient to form a wearable patch for sweat-based diabetes monitoring and feedback therapy. The stretchable device features a serpentine bilayer of gold mesh and gold-doped graphene that forms an efficient electrochemical interface for the stable transfer of electrical signals. The patch consists of a heater, temperature, humidity, glucose and pH sensors and polymeric microneedles that can be thermally activated to deliver drugs transcutaneously. We show that the patch can be thermally actuated to deliver Metformin and reduce blood glucose levels in diabetic mice.

Multifunctional Fe3O4/TaOx Core/Shell Nanoparticles for Simultaneous Magnetic Resonance Imaging and X-ray Computed Tomography

Multimodal imaging is highly desirable for accurate diagnosis because it can provide complementary information from each imaging modality. In this study, a sol-gel reaction of tantalum(V) ethoxide in a microemulsion containing Fe(3)O(4) nanoparticles (NPs) was used to synthesize multifunctional Fe(3)O(4)/TaO(x) core/shell NPs, which were biocompatible and exhibited a prolonged circulation time. When the NPs were intravenously injected, the tumor-associated vessel was observed using computed tomography (CT), and magnetic resonance imaging (MRI) revealed the high and low vascular regions of the tumor.

Wearable/disposable sweat-based glucose monitoring device with multistage transdermal drug delivery module

A sweat-based glucose monitoring device with transdermal drug delivery is developed for noninvasive diabetes treatment. Electrochemical analysis of sweat using soft bioelectronics on human skin provides a new route for noninvasive glucose monitoring without painful blood collection. However, sweat-based glucose sensing still faces many challenges, such as difficulty in sweat collection, activity variation of glucose oxidase due to lactic acid secretion and ambient temperature changes, and delamination of the enzyme when exposed to mechanical friction and skin deformation. Precise point-of-care therapy in response to the measured glucose levels is still very challenging. We present a wearable/disposable sweat-based glucose monitoring device integrated with a feedback transdermal drug delivery module. Careful multilayer patch design and miniaturization of sensors increase the efficiency of the sweat collection and sensing process. Multimodal glucose sensing, as well as its real-time correction based on pH, temperature, and humidity measurements, maximizes the accuracy of the sensing. The minimal layout design of the same sensors also enables a strip-type disposable device. Drugs for the feedback transdermal therapy are loaded on two different temperature-responsive phase change nanoparticles. These nanoparticles are embedded in hyaluronic acid hydrogel microneedles, which are additionally coated with phase change materials. This enables multistage, spatially patterned, and precisely controlled drug release in response to the patient’s glucose level. The system provides a novel closed-loop solution for the noninvasive sweat-based management of diabetes mellitus.

Bioresorbable Electronic Stent Integrated with Therapeutic Nanoparticles for Endovascular Diseases

Implantable endovascular devices such as bare metal, drug eluting, and bioresorbable stents have transformed interventional care by providing continuous structural and mechanical support to many peripheral, neural, and coronary arteries affected by blockage. Although effective in achieving immediate restoration of blood flow, the long-term re-endothelialization and inflammation induced by mechanical stents are difficult to diagnose or treat. Here we present nanomaterial designs and integration strategies for the bioresorbable electronic stent with drug-infused functionalized nanoparticles to enable flow sensing, temperature monitoring, data storage, wireless power/data transmission, inflammation suppression, localized drug delivery, and hyperthermia therapy. In vivo and ex vivo animal experiments as well as in vitro cell studies demonstrate the previously unrecognized potential for bioresorbable electronic implants coupled with bioinert therapeutic nanoparticles in the endovascular system.

In vivo Imaging of Tumor Transduced with Bimodal Lentiviral Vector Encoding Human Ferritin and Green Fluorescent Protein on a 1.5T Clinical Magnetic Resonance Scanner

A combination of reporter genes for magnetic resonance imaging (MRI) and optical imaging can provide an additional level of noninvasive and quantitative information about biological processes occurring in deep tissues. We developed a bimodal lentiviral vector to monitor deep tissue events using MRI to detect myc-tagged human ferritin heavy chain (myc-hFTH) expression and fluorescence imaging to detect green fluorescent protein (GFP) expression. The transgene construct was stably transfected into MCF-7 and F-98 cells. After transplantation of the cells expressing myc-hFTH and GFP into mice or rats, serial MRI and fluorescence imaging were performed with a human wrist coil on a 1.5T MR scanner and optical imaging analyzer for 4 weeks. No cellular toxicity due to overexpression of myc-hFTH and GFP was observed in MTT and trypan blue exclusion assays. Iron accumulation was observed in myc-hFTH cells and tumors by Prussian blue staining and iron binding assays. The myc-hFTH cells and tumors had significantly lower signal intensities in T(2)-weighted MRI than mock-transfected controls (P ≤ 0.05). This is direct evidence that myc-hFTH expression can be visualized noninvasively with a 1.5T clinical MR scanner. This study shows that MRI and fluorescence imaging of transplanted cells at molecular and cellular levels can be performed simultaneously using our bimodal lentiviral vector system. Our techniques can be used to monitor tumor growth, metastasis, and regression during cell and gene-based therapy in deep tissues.

An endoscope with integrated transparent bioelectronics and theranostic nanoparticles for colon cancer treatment

The gastrointestinal tract is a challenging anatomical target for diagnostic and therapeutic procedures for bleeding, polyps and cancerous growths. Advanced endoscopes that combine imaging and therapies within the gastrointestinal tract provide an advantage over stand-alone diagnostic or therapeutic devices. However, current multimodal endoscopes lack the spatial resolution necessary to detect and treat small cancers and other abnormalities. Here we present a multifunctional endoscope-based interventional system that integrates transparent bioelectronics with theranostic nanoparticles, which are photoactivated within highly localized space near tumours or benign growths. These advanced electronics and nanoparticles collectively enable optical fluorescence-based mapping, electrical impedance and pH sensing, contact/temperature monitoring, radio frequency ablation and localized photo/chemotherapy, as the basis of a closed-loop solution for colon cancer treatment. In vitro, ex vivo and in vivo experiments highlight the utility of this technology for accurate detection, delineation and rapid targeted therapy of colon cancer or precancerous lesions.

The Role of Perfusion CT as a Follow-up Modality After Transcatheter Arterial Chemoembolization An Experimental Study in a Rabbit Model

Objectives:To prospectively evaluate the feasibility of perfusion CT as a follow-up modality after transcatheter arterial chemoembolization (TACE) and to compare these findings with those of histopathology as the reference standard in a VX2 tumor rabbit model. Materials and Methods:VX2 carcinoma tumors were implanted into the liver of 20 rabbits 3 weeks prior to TACE. Perfusion CT was performed prior to TACE and 1- and 4-week after TACE. After obtaining perfusion index maps on perfusion CT, 2 radiologists measured the parametric perfusion indices of blood flow (BF), blood volume (BV), mean transit time (MTT), permeability of the capillary vessel surface (PS), and hepatic arterial fraction (HAF) of primary tumors on pre-TACE perfusion CT, chemoembolized primary tumors on 1-week perfusion CT, and recurred tumors on 4-week perfusion CT. The normal liver parenchyma indices were also recorded. In addition, the radiologists investigated the presence of a recurred tumor adjacent to the chemoembolized area on perfusion index maps of 4-week CT images. The areas of higher hepatic blood flow (HBF), hepatic blood volume (HBV), PS, and HAF, and lower MTT on 4-week perfusion CT than the normal liver parenchyma and the identical area on 1-week perfusion CT were considered as recurred tumors. Histopathology revealed the presence of a recurred tumor, and mean vessel density (MVD) was determined by immunochemical staining for CD31. CT perfusion indices were compared by use of the t test. Comparisons were made for the primary tumor versus normal liver parenchyma on pre-TACE CT, the primary tumor on pre-TACE CT versus the chemoembolized tumor on 1-week CT, the recurred tumor on 4-week CT versus the identical area on 1-week CT, and the primary tumor on pre-TACE CT versus the recurred tumor on 4-week CT. For the detection of recurred tumors, the sensitivity and specificity for 4-week perfusion CT were calculated. Correlation analysis between the recurred tumor perfusion indices and the MVD of the corresponding tumor region was performed. Among 20 rabbits, 6 were excluded from the analysis, and results were based on 14 rabbits. Results:Recurred tumors were histologically proven in 8 of 14 rabbits (57.1%). The BF, BV, PS, and HAF indices of primary tumors were significantly higher, whereas the MTT was significantly lower than that of the normal liver parenchyma on pre-TACE perfusion CT and that of chemoembolized areas on 1-week perfusion CT (P < 0.05). In addition, recurred tumors also showed significantly higher BF, BV, PS, and HAF, and lower MTT indices than the identical areas on 1-week perfusion CT (P < 0.05). The perfusion indices of recurred tumors were not significantly different from the indices of primary tumors (P > 0.05). Both sensitivity and specificity were 100% for 4-week perfusion CT. There were significant positive correlations between BF (r = 0.947), BV (r = 0.758), PS (r = 0.759), HAF (r = 0.955), and MVD in recurred tumors, and a significant inverse correlation between MTT (r = −0.782) and MVD was observed (P < 0.05). Conclusions:We believe that perfusion CT is a feasible alternative modality for the successful early response assessment and early detection of a marginally recurred tumor after TACE. However, perfusion CT has limitations for the prediction of tumor recurrence after TACE.

Continuous O2-Evolving MnFe2O4 Nanoparticle-Anchored Mesoporous Silica Nanoparticles for Efficient Photodynamic Therapy in Hypoxic Cancer

Therapeutic effects of photodynamic therapy (PDT) are limited by cancer hypoxia because the PDT process is dependent on O2 concentration. Herein, we design biocompatible manganese ferrite nanoparticle-anchored mesoporous silica nanoparticles (MFMSNs) to overcome hypoxia, consequently enhancing the therapeutic efficiency of PDT. By exploiting the continuous O2-evolving property of MnFe2O4 nanoparticles through the Fenton reaction, MFMSNs relieve hypoxic condition using a small amount of nanoparticles and improve therapeutic outcomes of PDT for tumors in vivo. In addition, MFMSNs exhibit T2 contrast effect in magnetic resonance imaging (MRI), allowing in vivo tracking of MFMSNs. These findings demonstrate great potential of MFMSNs for theranostic agents in cancer therapy.

Electromechanical cardioplasty using a wrapped elasto-conductive epicardial mesh

A mesh made of a conductive nanowire composite can be wrapped around the heart to improve hemodynamics in experimental heart failure in rodents. An electromechanical hug for the heart Heart failure can be treated by pacemakers to keep the beats in rhythm, but pacemakers apply electrical stimulation at specific points and do not provide comprehensive coverage of the entire organ. Park and colleagues therefore devised an electric mesh that wraps around the heart to deliver electrical impulses to the whole ventricular myocardium. The heart wrap was made from silver nanowires embedded in a rubber polymer that could conform to the unique three-dimensional anatomy of different hearts. In rats that had a heart attack, the mesh integrated structurally and electrically with the myocardium and exerted beneficial effects, including preserved diastolic relaxation, reduced wall stress, and improved cardiac contractile function. The mesh also terminated induced ventricular arrhythmia, acting as an epicardial defibrillator. Such epicardial meshes have been tested in clinical trials before and were effective in preventing ventricular remodeling but showed controversial results in long-term survival. The authors hope that their device, which is designed to integrate more faithfully with the heart’s structure and electrical conduction system, is more consistent in people. Heart failure remains a major public health concern with a 5-year mortality rate higher than that of most cancers. Myocardial disease in heart failure is frequently accompanied by impairment of the specialized electrical conduction system and myocardium. We introduce an epicardial mesh made of electrically conductive and mechanically elastic material, to resemble the innate cardiac tissue and confer cardiac conduction system function, to enable electromechanical cardioplasty. Our epicardium-like substrate mechanically integrated with the heart and acted as a structural element of cardiac chambers. The epicardial device was designed with elastic properties nearly identical to the epicardial tissue itself and was able to detect electrical signals reliably on the moving rat heart without impeding diastolic function 8 weeks after induced myocardial infarction. Synchronized electrical stimulation over the ventricles by the epicardial mesh with the high conductivity of 11,210 S/cm shortened total ventricular activation time, reduced inherent wall stress, and improved several measures of systolic function including increases of 51% in fractional shortening, ~90% in radial strain, and 42% in contractility. The epicardial mesh was also capable of delivering an electrical shock to terminate a ventricular tachyarrhythmia in rodents. Electromechanical cardioplasty using an epicardial mesh is a new pathway toward reconstruction of the cardiac tissue and its specialized functions.