Passive and Flexible Wireless Electronics Fabricated on Parylene/PDMS Substrate for Stimulation of Human Stem Cell-Derived Cardiomyocytes.

In this paper, we report the development of a wireless, passive, biocompatible, and flexible system for stimulation of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMS). Fabricated on a transparent parylene/PDMS substrate, the proposed stimulator enables real-time excitation and characterization of hiPSC-CMs cultured on-board. The device comprises a rectenna operating at 2.35 GHz which receives radio frequency (RF) energy from an external transmitter and converts it into DC voltage to deliver monophasic stimulation. The operation of the stimulator was primarily verified by delivering monophasic voltage pulses through gold electrodes to hiPSC-CMs cultured on the Matrigel-coated substrates. Stimulated hiPSC-CMs beat in accordance with the monophasic pulses when delivered at 0.5, 1, and 2 Hz pulsing frequency, while no significant cell death was observed. The wireless stimulator could generate monophasic pulses with an amplitude of 8 V at a distance of 15 mm. These results demonstrated the proposed wireless stimulator's efficacy for providing electrical stimulation to engineered cardiac tissues. The proposed stimulator will have a wide application in tissue engineering where a fully wireless stimulation of electroconductive cells is needed. The device also has potential to be employed as a cardiac stimulator by delivering external stimulation and regulating the contractions of cardiac tissue.

Wireless Wearable Ultrasound Sensor to Characterize Respiratory Behavior.

A wireless wearable sensor on a paper substrate was used to continuously monitor respiratory behavior that can extract and deliver clinically relevant respiratory parameters to a smartphone. Intended to be placed horizontally at the midpoint of the costal margin and the xiphoid process as determined through anatomical analysis and experimental test, the wearable sensor is compact at only 40 × 35 × 6 mm3 in size and 6.5 g weight including a 2.7 g lithium battery. The wearable sensor, consisting of an ultrasound emitter, an ultrasound receiver, wireless transmission system, and associated data acquisition, measures the linear change in circumference at the attachment location by recording and analyzing the changes in ultrasound pressure as the distance between the emitter and the receiver changes. Changes in ultrasound pressure corresponding to linear strain are converted to temporal lung volume data and are wirelessly transmitted to an associated custom-designed smartphone app. Processing the received data, the mobile app is able to display the temporal volume trace and the flow rate vs. volume loop graphs, which are standard plots used to analyze respiration. From the plots, the app is able to extract and display clinically relevant respiration parameters, including forced expiratory volume delivered in the first second of expiration (FEV1) and forced vital capacity (FVC). The sensor was evaluated with eight volunteers, showing a mean difference of the FEV1/FVC ratio as bounded by 0.00-4.25% when compared to the industry-standard spirometer results. By enabling continuous tracking of respiratory behavioral parameters, the wireless wearable sensor helps monitor the progression of chronic respiratory illnesses, including providing warnings to asthma patients and caregivers to pursue necessary medical assistance.

A Wireless Fully-Passive Acquisition of Biopotentials.

Biopotential signals contain essential information for assessing the functionality of organs and diagnosing diseases. We present a flexible sensor, capable of measuring biopotentials, in real time, in a wireless and fully-passive manner. The flexible sensor collects and transmits biopotentials to an external reader without wire, battery, or harvesting/regulating element. The sensor is fabricated on a 90 µm-thick polyimide substrate with a footprint of 18 × 15 × 0.5 mm3. The wireless fully-passive acquisition of biopotentials is enabled by the RF (Radio Frequency) microwave backscattering effect where the biopotentials are modulated by an array of varactors with incoming RF carrier that is backscattered to the external reader. The flexile sensor is verified and validated by emulated signal and electrocardiogram (ECG), electromyogram (EMG), and electrooculogram (EOG), respectively. A deep learning algorithm analyzes the signal quality of wirelessly acquired data, along with the data from commercially available wired sensor counterparts. Wired and wireless data shows <3% discrepancy in deep learning testing accuracy for ECG and EMG up to the wireless distance of 240 mm. Wireless acquisition of EOG further demonstrates accurate tracking of horizontal eye movement with deep learning training and testing accuracy reaching up to 93.6% and 92.2%, respectively, indicating successful detection of biopotentials signal as low as 250 µVPP. These findings support that the real-time wireless fully-passive acquisition of on-body biopotentials is indeed feasible and may find various uses for future clinical research.

Machine-learning enabled wireless wearable sensors to study individuality of respiratory behaviors.

Respiratory behaviors provide useful measures of lung health. The current methods have limited capabilities of continuous characterization of respiratory behaviors, often required to assess respiratory disorders and diseases. This work presents a system equipped with a machine learning algorithm, capable of continuously monitoring respiratory behaviors. The system, consisting of two wireless wearable sensors, accurately extracts and classifies the features of respiratory behaviors of subjects within various postures, wirelessly transmitting the temporal respiratory behaviors to a laptop. The sensors were attached on the midway of the xiphoid process and the costal margin, and 1 cm above the umbilicus, respectively. The wireless wearable sensor, consisting of ultrasound emitter, ultrasound receiver, data acquisition and wireless transmitter, has a small footprint and light weight. The sensors correlate the mechanical strain at wearing sites to lung volume by measuring the local circumference changes of the chest and abdominal walls simultaneously. Eleven subjects were recruited to evaluate the wireless wearable sensors. Three different random forest classifiers, including generic, individual, and weighted-adaptive classifiers, were used to process the wireless data of the subjects at four different postures. The results demonstrate the respiratory behaviors are individual- and posture-dependent. The generic classifier merely reaches the accuracy of classifying postures of 21.9 ± 1.7% while individual and weighted-adaptive classifiers mark substantially high, up to 98.9 ± 0.6% and 98.8 ± 0.6%, respectively. The accurate monitoring of respiratory behaviors can track the progression of respiratory disorders and diseases, including chronic respiratory obstructive disease (COPD), asthma, apnea, and others for timely and objective approaches for control.

Three-Dimensionally Printed Microelectromechanical-System Hydrogel Valve for Communicating Hydrocephalus.

Hydrocephalus (HCP) is a chronic neurological brain disorder caused by a malfunction of the cerebrospinal fluid (CSF) drainage mechanism in the brain. The current standard method to treat HCP is a shunt system. Unfortunately, the shunt system suffers from complications including mechanical malfunctions, obstructions, infections, blockage, breakage, overdrainage, and/or underdrainage. Some of these complications may be attributed to the shunts' physically large and lengthy course making them susceptible to external forces, siphoning effects, and risks of infection. Additionally, intracranial catheters artificially traverse the brain and drain the ventricle rather than the subarachnoid space. We report a 3D-printed microelectromechanical system-based implantable valve to improve HCP treatment. This device provides an alternative approach targeting restoration of near-natural CSF dynamics by artificial arachnoid granulations (AGs), natural components for CSF drainage in the brain. The valve, made of hydrogel, aims to regulate the CSF flow between the subarachnoid space and the superior sagittal sinus, in essence, substituting for the obstructed arachnoid granulations. The valve, operating in a fully passive manner, utilizes the hydrogel swelling feature to create nonzero cracking pressure, PT ≈ 47.4 ± 6.8 mmH2O, as well as minimize reverse flow leakage, QO ≈ 0.7 µL/min on benchtop experiments. The additional measurements performed in realistic experimental setups using a fixed sheep brain also deliver comparable results, PT ≈ 113.0 ± 9.8 mmH2O and QO ≈ 3.7 µL/min. In automated loop functional tests, the valve maintains functionality for a maximum of 1536 cycles with the PT variance of 44.5 mmH2O < PT < 61.1 mmH2O and negligible average reverse flow leakage rates of ∼0.3 µL/min.

Fully Passive Flexible Wireless Neural Recorder for the Acquisition of Neuropotentials from a Rat Model.

Wireless implantable neural interfaces can record high-resolution neuropotentials without constraining patient movement. Existing wireless systems often require intracranial wires to connect implanted electrodes to an external head stage or/and deploy an application-specific integrated circuit (ASIC), which is battery-powered or externally power-transferred, raising safety concerns such as infection, electronics failure, or heat-induced tissue damage. This work presents a biocompatible, flexible, implantable neural recorder capable of wireless acquisition of neuropotentials without wires, batteries, energy harvesting units, or active electronics. The recorder, fabricated on a thin polyimide substrate, features a small footprint of 9 mm × 8 mm × 0.3 mm and is composed of passive electronic components. The absence of active electronics on the device leads to near zero power consumption, inherently avoiding the catastrophic failure of active electronics. We performed both in vitro validation in a tissue-simulating phantom and in vivo validation in an epileptic rat. The fully passive wireless recorder was implanted under rat scalp to measure neuropotentials from its contact electrodes. The implanted wireless recorder demonstrated its capability to capture low voltage neuropotentials, including somatosensory evoked potentials (SSEPs), and interictal epileptiform discharges (IEDs). Wirelessly recorded SSEP and IED signals were directly compared to those from wired electrodes to demonstrate the efficacy of the wireless data. In addition, a convoluted neural network-based machine learning algorithm successfully achieved IED signal recognition accuracy as high as 100 and 91% in wired and wireless IED data, respectively. These results strongly support the fully passive wireless neural recorder's capability to measure neuropotentials as low as tens of microvolts. With further improvement, the recorder system presented in this work may find wide applications in future brain machine interface systems.

A wireless fully-passive acquisition of biopotentials.

Biopotential signals contain essential information for assessing functionality of organs and diagnosing diseases. We present a flexible sensor, capable of measuring biopotentials, in real time, in wireless and fully-passive manner. The flexible sensor collects and transmits biopotentials to an external reader without wire, battery, or harvesting/regulating element. The sensor is fabricated on a 90 µm-thick polyimide substrate with footprint of 18 × 15 × 0.5 mm3. The wireless fully-passive acquisition of biopotentials is enabled by the RF (Radio Frequency) microwave backscattering effect where the biopotentials are modulated by an array of varactors with incoming RF carrier that is backscattered to the external reader. The flexile sensor is verified and validated by emulated signal and Electrocardiogram (ECG), Electromyogram (EMG), and Electrooculogram (EOG), respectively. A deep learning algorithm analyzes the signal quality of wirelessly acquired data, along with the data from commercially-available wired sensor counterparts. Wired and wireless data shows <3% discrepancy in deep learning testing accuracy for ECG and EMG up to the wireless distance of 240 mm. Wireless acquisition of EOG further demonstrates accurate tracking of horizontal eye movement with deep learning training and testing accuracy reaching up to 93.6% and 92.2%, respectively, indicating successful detection of biopotentials signal as low as 250 µVPP. These findings support that the real-time wireless fully-passive acquisition of on-body biopotentials is indeed feasible and may find various uses for future clinical research.

Wireless Wearable Ultrasound Sensor on a Paper Substrate to Characterize Respiratory Behavior.

Respiratory behavior contains crucial parameters to feature lung functionality, including respiratory rate, profile, and volume. The current well-adopted method to characterize respiratory behavior is spirometry using a spirometer, which is bulky, heavy, expensive, requires a trained provider to operate, and is incapable of continuous monitoring of respiratory behavior, which is often critical to assess chronic respiratory diseases. This work presents a wireless wearable sensor on a paper substrate that is capable of continuous monitoring of respiratory behavior and delivering the clinically relevant respiratory information to a smartphone. The wireless wearable sensor was attached on the midway of the xiphoid process and the costal margin, corresponding to the abdomen-apposed rib cage, based on the anatomical and experimental analysis. The sensor, with a footprint of 40 × 35 × 6 mm3 and weighing 6.5 g, including a 2.7 g battery, consists of three subsystems, (i) ultrasound emitter, (ii) ultrasound receiver, and (iii) data acquisition and wireless transmitter. The sensor converts the linear strain at the wearing site to the lung volume change by measuring the change in ultrasound pressure as a function of the distance between the emitter and the receiver. The temporal lung volume change data, directly converted from the ultrasound pressure, is wirelessly transmitted to a smartphone where a custom-designed app computes to show volume-time and flow rate-volume loop graphs, standard respiratory analysis plots. The app analyzes the plots to show the clinically relevant respiratory behavioral parameters, such as forced vital capacity (FVC) and forced expiratory volume delivered in the first second (FEV1). Potential user-induced error on sensor placement and temperature sensitivity were studied to demonstrate the sensor maintains its performance within a reasonable range of those variables. Eight volunteers were recruited to evaluate the sensor, which showed the mean deviation of the FEV1/FVC ratio in the range of 0.00-4.25% when benchmarked by the spirometer. The continuous measurement of respiratory behavioral parameters helps track the progression of the respiratory diseases, including asthma progression to provide alerts to relevant caregivers to seek needed timely treatment.

Microbial activity influences electrical conductivity of biofilm anode.

This study assessed the conductivity of a Geobacter-enriched biofilm anode in a microbial electrochemical cell (MxC) equipped with two gold anodes (25 mM acetate medium), as different proton gradients were built throughout the biofilm. There was no pH gradient across the biofilm anode at 100 mM phosphate buffer (current density 2.38 A/m2) and biofilm conductivity (Kbio) was as high as 0.87 mS/cm. In comparison, an inner biofilm became acidic at 2.5 mM phosphate buffer in which dead cells were accumulated at ∼80 µm of the inner biofilm anode. At this low phosphate buffer, Kbio significantly decreased by 0.27 mS/cm, together with declined current density of 0.64 A/m2. This work demonstrates that biofilm conductivity depends on the composition of live and dead cells in the conductive biofilm anode.

Wireless Passive Stimulation of Engineered Cardiac Tissues.

We present a battery-free radio frequency (RF) microwave activated wireless stimulator, 25 × 42 × 1.6 mm3 on a flexible substrate, featuring high current delivery, up to 60 mA, to stimulate engineered cardiac tissues. An external antenna shines 2.4 GHz microwave, which is modulated by an inverted pulse to directly control the stimulating waveform, to the wireless passive stimulator. The stimulator is equipped with an on-board antenna, multistage diode multipliers, and a control transistor. Rat cardiomyocytes, seeded on electrically conductive gelatin-based hydrogels, demonstrate synchronous contractions and Ca2+ transients immediately upon stimulation. Notably, the stimulator output voltage and current profiles match the tissue contraction frequency within 0.5-2 Hz. Overall, our results indicate the promising potential of the proposed wireless passive stimulator for cardiac stimulation and therapy by induction of precisely controlled and synchronous contractions.

The Roles of Biofilm Conductivity and Donor Substrate Kinetics in a Mixed-Culture Biofilm Anode.

We experimentally assessed the kinetics and thermodynamics of electron transfer (ET) from the donor substrate (acetate) to the anode for a mixed-culture biofilm anode. We interpreted the results with a modified biofilm-conduction model consisting of three ET steps in series: (1) intracellular ET, (2) non-Ohmic extracellular ET (EET) from an outer membrane protein to an extracellular cofactor (EC), and (3) ET from the EC to the anode by Ohmic-conduction in the biofilm matrix. The steady-state current density was 0.82 ± 0.03 A/m2 in a miniature microbial electrochemical cell operated at fixed anode potential of -0.15 V versus the standard hydrogen electrode. Illumina 16S-rDNA and -rRNA sequences showed that the Geobacter genus was less than 30% of the community of the biofilm anode. Biofilm conductivity was high at 2.44 ± 0.42 mS/cm, indicating that the maximum current density could be as high as 270 A/m2 if only Ohmic-conduction EET was limiting. Due to the high biofilm conductivity, the maximum energy loss for Ohmic-conduction EET was negligible, 0.085 mV. The energy loss in the second ET step also was small, only 20 mV, and the potential for the EC involved in the second ET was -0.15 V, a value documenting that >99% of the EC was in the oxidized state. Monod kinetics for utilization of acetate were relatively slow, and at least 87% of the energy loss was in the intracellular step. Thus, intracellular ET was the main kinetic and thermodynamic bottleneck to ET from donor substrate to the anode for a highly conductive biofilm.

A miniaturized microbial fuel cell with three-dimensional graphene macroporous scaffold anode demonstrating a record power density of over 10,000 W m(-3) .

A microbial fuel cell (MFC) is a bio-inspired renewable energy converter which directly converts biomass into electricity. This is accomplished via the unique extracellular electron transfer (EET) of a specific species of microbe called the exoelectrogen. Many studies have attempted to improve the power density of MFCs, yet the reported power density is still nearly two orders of magnitude lower than other power sources/converters. Such a low performance can primarily be attributed to two bottlenecks: (i) ineffective electron transfer from microbes located far from the anode and (ii) an insufficient buffer supply to the biofilm. This work takes a novel approach to mitigate these two bottlenecks by integrating a three-dimensional (3D) macroporous graphene scaffold anode in a miniaturized MFC. This implementation has delivered the highest power density reported to date in all MFCs of over 10,000 W m(-3). The miniaturized configuration offers a high surface area to volume ratio and improved mass transfer of biomass and buffers. The 3D graphene macroporous scaffold warrants investigation due to its high specific surface area, high porosity, and excellent conductivity and biocompatibility which facilitates EET and alleviates acidification in the biofilm. Consequently, the 3D scaffold houses an extremely thick and dense biofilm from the Geobacter-enriched culture, delivering an areal/volumetric current density of 15.51 A m(-2)/31,040 A m(-3) and a power density of 5.61 W m(-2)/11,220 W m(-3), a 3.3 fold increase when compared to its planar two-dimensional (2D) control counterparts.

Low Cytotoxicity and Genotoxicity of Two-Dimensional MoS2 and WS2.

Atomically thin transition-metal dichalcogenides (TMDs) have attracted considerable interest because of their unique combination of properties, including photoluminescence, high lubricity, flexibility, and catalytic activity. These unique properties suggest future uses for TMDs in medical applications such as orthodontics, endoscopy, and optogenetics. However, few studies thus far have investigated the biocompatibility of mechanically exfoliated and chemical vapor deposition (CVD)-grown pristine two-dimensional TMDs. Here, we evaluate pristine molybdenum disulfide (MoS2) and tungsten disulfide (WS2) in a series of biocompatibility tests, including live-dead cell assays, reactive oxygen species (ROS) generation assays, and direct assessment of cellular morphology of TMD-exposed human epithelial kidney cells (HEK293f). Genotoxicity and genetic mutagenesis were also evaluated for these materials via the Ames Fluctuation test with the bacterial strain S. typhimurium TA100. Scanning electron microscopy of cultured HEK293f cells in direct contact with MoS2 and WS2 showed no impact on cell morphology. HEK293f cell viability, evaluated by both live-dead fluorescence labeling to detect acute toxicity and ROS to monitor for apoptosis, was unaffected by these materials. Exposure of bacterial cells to these TMDs failed to generate genetic mutation. Together, these findings demonstrate that neither mechanically exfoliated nor CVD-grown TMDs are deleterious to cellular viability or induce genetic defects. Thus, these TMDs appear biocompatible for future application in medical devices.

Rapid bladder cancer cell detection from clinical urine samples using an ultra-thin silicone membrane.

Early detection of initial onset, as well as recurrence, of cancer is paramount for improved patient prognosis and human health. Cancer screening is enhanced by rapid differentiation of cancerous from non-cancerous cells which employs the inherent differences in biophysical properties. Our preliminary testing demonstrates that cell-line derived bladder cancer cells deform our <30 nm silicone membrane within an hour and induce visually distinct wrinkle patterns while cell-line derived non-cancerous cells fail to induce these wrinkle patterns. Herein, we report a platform for the rapid detection of cancerous cells from human clinical urine samples. We performed a blinded study with cells extracted from the urine of human patients suspected to have bladder cancer alongside healthy controls. Wrinkle patterns were induced specifically by the five cancer patient samples within 12 hours and not by the healthy controls. These results were independently validated by the standard diagnostic techniques cystoscopy and cytology. Thus, our ultra-thin membrane approach for cancer diagnosis appears as accurate as standard diagnostic methods while vastly more rapid, less invasive, and requiring limited expertise.

A Wireless Fully Passive Neural Recording Device for Unobtrusive Neuropotential Monitoring.

GOAL: We propose a novel wireless fully passive neural recording device for unobtrusive neuropotential monitoring. Previous work demonstrated the feasibility of monitoring emulated brain signals in a wireless fully passive manner. In this paper, we propose a novel realistic recorder that is significantly smaller and much more sensitive. METHODS: The proposed recorder utilizes a highly efficient microwave backscattering method and operates without any formal power supply or regulating elements. Also, no intracranial wires or cables are required. In-vitro testing is performed inside a four-layer head phantom (skin, bone, gray matter, and white matter). RESULTS: Compared to our former implementation, the neural recorder proposed in this study has the following improved features: 1) 59% smaller footprint, 2) up to 20-dB improvement in neuropotential detection sensitivity, and 3) encapsulation in biocompatible polymer. CONCLUSION: For the first time, temporal emulated neuropotentials as low as 63 µVpp can be detected in a wireless fully passive manner. Remarkably, the high-sensitivity achieved in this study implies reading of most neural signals generated by the human brain. SIGNIFICANCE: The proposed recorder brings forward transformational possibilities in wireless fully passive neural detection for a very wide range of applications (e.g., epilepsy, Alzheimer's, mental disorders, etc.).

In vitro hydrodynamic, transient, and overtime performance of a miniaturized valve for hydrocephalus.

Reliable cerebrospinal fluid (CSF) draining methods are needed to treat hydrocephalus, a chronic debilitating brain disorder. Current shunt implant treatments are characterized by high failure rates that are to some extent attributed to their length and multiple components. The designed valve, made of hydrogel, steers away from such protracted schemes and intends to provide a direct substitute for faulty arachnoid granulations, the brain's natural CSF draining valves, and restore CSF draining operations within the cranium. The valve relies on innate hydrogel swelling phenomena to strengthen reverse flow sealing at idle and negative pressures thereby alleviating common valve failure mechanisms. In vitro measurements display operation in range of natural CSF draining (cracking pressure, PT ~ 1-110 mmH2O and outflow hydraulic resistance, Rh ~ 24-152 mmH2O/mL/min), with negligible reverse flow leakage (flow, QO > -10 µL/min). Hydrodynamic measurements and over-time tests under physically relevant conditions further demonstrate the valve's operationally-reproducible properties and strengthen its validity for use as a chronic implant.

Improved current and power density with a micro-scale microbial fuel cell due to a small characteristic length.

A microbial fuel cell (MFC) is a bio-electrochemical converter that can extract electricity from biomass by the catabolic reaction of microorganisms. This work demonstrates the impact of a small characteristic length in a Geobacteraceae-enriched, micro-scale microbial fuel cell (MFC) that achieved a high power density. The small characteristic length increased the surface-area-to-volume ratio (SAV) and the mass transfer coefficient. Together, these factors made it possible for the 100-µL MFC to achieve among the highest areal and volumetric power densities - 83 µW/cm(2) and 3300 µW/cm(3), respectively - among all micro-scale MFCs to date. Furthermore, the measured Coulombic efficiency (CE) was at least 79%, which is 2.5-fold greater than the previously reported maximum CE in micro-scale MFCs. The ability to improve these performance metrics may make micro-scale MFCs attractive for supplying power in sub-100 µW applications, especially in remote or hazardous conditions, where conventional powering units are hard to establish.

Detection of copper ions in drinking water using the competitive adsorption of proteins.

Heavy metal ions, i.e., Cu(2+), are harmful to the environment and our health. In order to detect them, and circumvent or alleviate the weaknesses of existing detecting technologies, we contrive a unique Surface Plasmon Resonance (SPR) biosensor combined with competitive adsorption of proteins, termed the Vroman effect. This approach adopts native proteins (albumin) as bio-receptors that interact with Cu(2+) to be denatured. Denaturation disrupts the conformation of albumin so that it weakens its affinity to adsorb on the sensing surface. Through the competitive adsorption between the denatured albumins and the native ones, the displacement occurs adjacent to the sensing surface, and this process is real-time monitored by SPR, a surface-sensitive label-free biosensor. The affinities of native albumin is significantly higher than that of denatured albumin, demonstrated by measured KD of native and denatured albumin to gold surafce, 5.8±0.2×10(-5) M and 5.4±0.1×10(-4) M, respectively. Using our biosensor, Cu(2+) with concentration down to 0.1mg/L is detected in PBS, tap water, deionized water, and bottled water. The SPR biosensor is characterized for 5 different heavy metal ions, Cu(2+), Fe(3+), Mn(2+), Pb(2+), and Hg(2+), most common heavy metal ions found in tap water. At the maximum contaminant level (MCL) suggested by the United States Environmental Protection Agency (EPA), the SPR biosensor produces 13.5±0.4, 1.5±0.4, 0, 0, and 0 mDeg, respectively, suggesting the biosensor may be used to detect Cu(2+) in tap water samples.

Evaluation of the effect of a 0.0584% hydrocortisone aceponate spray on clinical signs and skin barrier function in dogs with atopic dermatitis.

The purpose of this study was to evaluate the effects of a topical spray containing 0.0584% hydrocortisone aceponate (HCA) on canine atopic dermatitis (CAD) and to evaluate the skin barrier function during the treatment of CAD. Twenty-one dogs that fulfilled the diagnostic criteria for CAD were included in this study. The HCA spray was applied once a day to the lesions of all dogs for 7 or 14 days. Clinical assessment was performed before (day 0) and after treatment (day 14), and clinical responses were correlated with changes in skin barrier function. CAD severity significantly decreased after 14 days of HCA treatment based on the lesion scores (p < 0.0001), which were determined using the CAD extent and severity index (CADESI-03) and pruritus scores (p < 0.0001) calculated using a pruritus visual analog scale. Transepidermal water loss, a biomarker of skin barrier function, was significantly reduced compared to baseline (day 0) measurements (p = 0.0011). HCA spray was shown to be effective for significantly improving the condition of dogs suffering from CAD. This treatment also significantly improved cut.

Monitoring protein distributions based on patterns generated by protein adsorption behavior in a microfluidic channel.

We report a unique monitoring technique of protein distributions based on distinctive patterns generated by protein adsorption behavior on a solid surface in a microfluidic channel. Bare gold and COOH-modified self-assembled monolayer (SAM) sensing surfaces were pre-adsorbed with one of four different proteins: lysozyme, albumin, transferrin, or IgG. Each surface provides a thermodynamically governed platform for immobilizing proteins and generates analyte-specific response patterns. Each surface has its own thermodynamic energy governing pre-adsorbed protein behaviors, so that sample proteins react with the pre-adsorbed ones to different extents depending on their sizes, isoelectric points (pI), and characteristics of the sensing surfaces. Modified surfaces were mounted and monitored in real time using surface plasmon resonance (SPR). Buffer-prepared sample matrices (α1-antitrypsin, haptoglobin, C-reactive protein (CRP), and IgM) characterized protein response patterns. Each surface generated distinctive patterns based on individual SPR angle shifts. We classified each sample with 95% accuracy using linear discriminant analysis (LDA). Our method also discriminated between different concentrations of CRP in the cocktail sample, detecting concentrations as low as 1 nM with 91.7% accuracy. This technique may be integrated with a microfluidic lab-on-a-chip system and monitor the distribution of a specific group of proteins in human serum.