Integration of hydrogels in microfabrication processes for bioelectronic medicine: Progress and outlook.

Recent research aiming at the development of electroceuticals for the treatment of medical conditions such as degenerative diseases, cardiac arrhythmia and chronic pain, has given rise to microfabricated implanted bioelectronic devices capable of interacting with host biological tissues in synergistic modalities. Owing to their multimodal affinity to biological tissues, hydrogels have emerged as promising interface materials for bioelectronic devices. Here, we review the state-of-the-art and forefront in the techniques used by research groups for the integration of hydrogels into the microfabrication processes of bioelectronic devices, and present the manufacturability challenges to unlock their further clinical deployment.

Thermal Conductivity and Mechanical Properties of Polymer Composites with Hexagonal Boron Nitride-A Comparison of Three Processing Methods: Injection Moulding, Powder Bed Fusion and Casting.

Materials providing heat dissipation and electrical insulation are required for many electronic and medical devices. Polymer composites with hexagonal boron nitride (hBN) may fulfil such requirements. The focus of this study is to compare composites with hBN fabricated by injection moulding (IM), powder bed fusion (PBF) and casting. The specimens were characterised by measuring thermal conductivity, tensile properties, hardness and hBN particle orientation. A thermoplastic polyurethane (TPU) was selected as the matrix for IM and PBF, and an epoxy was the matrix for casting. The maximum filler weight fractions were 65%, 55% and 40% for IM, casting and PBF, respectively. The highest thermal conductivity (2.1 W/m∙K) was measured for an IM specimen with 65 wt% hBN. However, cast specimens had the highest thermal conductivity for a given hBN fraction. The orientation of hBN platelets in the specimens was characterised by X-ray diffraction and compared with numerical simulations. The measured thermal conductivities were discussed by comparing them with four models from the literature (the effective medium approximation model, the Ordóñez-Miranda model, the Sun model, and the Lewis-Nielsen model). These models predicted quite different thermal conductivities vs. filler fraction. Adding hBN increased the hardness and tensile modulus, and the tensile strength at high hBN fractions. The strength had a minimum as the function of filler fraction, while the strain at break decreased. These trends can be explained by two mechanisms which occur when adding hBN: reinforcement and embrittlement.

Remote Sensing System for Motor Nerve Impulse.

In this article, we present our research achievements regarding the development of a remote sensing system for motor pulse acquisition, as a first step towards a complete neuroprosthetic arm. We present the fabrication process of an implantable electrode for nerve impulse acquisition, together with an innovative wirelessly controlled system. In our study, these were combined into an implantable device for attachment to peripheral nerves. Mechanical and biocompatibility tests were performed, as well as in vivo testing on pigs using the developed system. This testing and the experimental results are presented in a comprehensive manner, demonstrating that the system is capable of accomplishing the requirements of its designed application. Most significantly, neural electrical signals were acquired and transmitted out of the body during animal experiments, which were conducted according to ethical regulations in the field.

Hybrid electrochemical sensor platform for capsaicin determination using coarsely stepped cyclic squarewave voltammetry.

A small, standalone electrochemical hybrid sensor platform, combining flexible electronics and screen-printed electrodes, is demonstrated in the determination of capsaicin through adsorptive stripping voltammetry. The sensing scheme was simplified to be compatible with a low-cost device. The simplification involved eliminating the need for additional modification of the electrode and employing a coarsely stepped squarewave voltammetry, a technique which is applicable with less sophisticated instrumentation. This architecture was found to be suitable for concentrations up to at least 5000 µM with a detection limit of 1.98 µM. The screen-printed carbon graphite electrodes were made reusable through an ethanol rinsing protocol. The effect of ethanol/buffer volumetric ratio in the test sample was shown to greatly influence the analytical data, and a fixed 10% (v/v) was chosen as a compromise between signal-to-noise ratio and not exceeding the solubility limit of the desired upper range.

Continuous monitoring of cardiac function by 3-dimensional accelerometers in a closed-chest pig model.

OBJECTIVES: Cardiac wall motions reflect systolic and diastolic function. We have previously demonstrated the ability of a miniaturized three-axis (3D) accelerometer to monitor left ventricular function in experimental models and in patients. The main aim of this study was to investigate the clinical utility of the method for monitoring the left and right ventricular function during changes in global and regional cardiac function in a postoperative closed-chest situation. METHODS: In 13 closed-chest pigs, miniaturized 3D accelerometers were placed on the left ventricle in the apical and basal regions and in the basal region of the right ventricle. An epicardial 3D motion vector was calculated from the acceleration signals in each heart region. Peak systolic velocity along this 3D vector (3D V(sys)) was compared with the positive time derivative of the left and right ventricular pressure and with cardiac index during changes in global LV function (unloading, fluid loading, esmolol, dobutamine) and with ultrasound during regional left ventricular dysfunction (3-min occlusion of the left anterior descending coronary artery). RESULTS: Significant and typical changes in accelerometer 3D V(sys) were seen in all heart regions during changes in global cardiac function. 3D V(sys) reflected the left and right ventricular contractility via significant correlations with the positive time derivative of the left and right ventricular pressure, r = 0.86 and r = 0.72, and with cardiac index r = 0.82 and r = 0.73 (all P < 0.001), respectively. The miniaturized accelerometers also detected regional dysfunction, but showed reduced ability to localize ischaemia as the 3D V(sys) in all heart regions showed similar reductions during coronary artery occlusion. CONCLUSIONS: Miniaturized 3D accelerometers placed on the heart can assess global and regional function in a closed-chest model. The technique may be used for continuous postoperative monitoring after cardiac surgery.

Fabrication and assembly of MEMS accelerometer-based heart monitoring device with simplified, one step placement.

An accelerometer-based heart monitoring system has been developed for real-time evaluation of heart wall movement. In this paper, assembly and fabrication of an improved device is presented along with system characterization and test data from an animal experiment. The new device is smaller and has simplified the implantation procedure compared to earlier prototypes. Leakage current recordings were well below those set by the corresponding standards.

Automatic real-time detection of myocardial ischemia by epicardial accelerometer.

OBJECTIVE: Myocardial ischemia may be detected with epicardial accelerometers. We developed and tested automated algorithms for real-time detection of myocardial ischemia by accelerometer measurements in both experimental and clinical settings. METHODS: In 10 pigs, an accelerometer was fixed to the epicardium in the area perfused by left anterior descending coronary artery. Acceleration and electrocardiogram were simultaneously recorded, and the QRS complex was automatically detected for exact timing of systole. Peak circumferential velocity and displacement were automatically calculated from epicardial acceleration signal within 150 milliseconds after peak R on electrocardiography. Global myocardial function was reduced by esmolol infusion, and regional function was altered by temporary left anterior descending occlusion. Automated ischemia detection analyses were tested in 7 patients during off-pump coronary artery bypass grafting. Left anterior descending coronary artery was occluded for 3 minutes before grafting. In both models, echocardiographic myocardial circumferential strain was used to confirm ischemia. RESULTS: Systolic displacement changed most during left anterior descending occlusion. Negative displacement during ischemia was found in pigs (11.5 +/- 2.3 to -1.2 +/- 2.8 mm, P < .01); regional hypokinesia was found in clinical study (12.8 +/- 8.1 to 3.5 +/- 4.4 mm, P < .01). Ischemia was confirmed by echocardiography in both settings. Esmolol infusion induced smaller changes in automated accelerometer measurements than did left anterior descending occlusion (P < .01). CONCLUSIONS: Automatic real-time detection of myocardial ischemia with epicardial accelerometer was feasible. Automated ischemia detection analysis may be used for continuous monitoring of myocardial ischemia during cardiac surgery.

Assembly and packaging of a three-axis micro accelerometer used for detection of heart infarction.

In coronary artery bypass grafting there is a risk of graft occlusion which may result in myocardial infarction. A three-axis acceleration sensor may give additional information about heart function during surgery and the first postoperative days. This paper describes the assembly and packaging of a three-axis micro acceleration sensor for use in clinical trials. The sensor was connected to a cable for power supply and signal output and moulded in silicone. Testing of the encapsulation showed leakage currents well below the 10 muA limit for direct cardiac applications. A hydrogen peroxide gas plasma method was used for sterilization. In animal experiments the sensor was sutured to the heart and no fatigue failures ensued due to the cycling strain forces from the heart. The sensor has been qualified for clinical trials.