silicon and Cardiovascular-Diseases

Cardiac rhythm management devices provide therapies for both arrhythmias and resynchronisation but not heart failure, which affects millions of patients worldwide. This paper reviews recent advances in biophysics and mathematical engineering that provide a novel technological platform for addressing heart disease and enabling beat-to-beat adaptation of cardiac pacing in response to physiological feedback. The technology consists of silicon hardware central pattern generators (hCPGs) that may be trained to emulate accurately the dynamical response of biological central pattern generators (bCPGs). We discuss the limitations of present CPGs and appraise the advantages of analog over digital circuits for application in bioelectronic medicine. To test the system, we have focused on the cardio-respiratory oscillators in the medulla oblongata that modulate heart rate in phase with respiration to induce respiratory sinus arrhythmia (RSA). We describe here a novel, scalable hCPG comprising physiologically realistic (Hodgkin-Huxley type) neurones and synapses. Our hCPG comprises two neurones that antagonise each other to provide rhythmic motor drive to the vagus nerve to slow the heart. We show how recent advances in modelling allow the motor output to adapt to physiological feedback such as respiration. In rats, we report on the restoration of RSA using an hCPG that receives diaphragmatic electromyography input and use it to stimulate the vagus nerve at specific time points of the respiratory cycle to slow the heart rate. We have validated the adaptation of stimulation to alterations in respiratory rate. We demonstrate that the hCPG is tuneable in terms of the depth and timing of the RSA relative to respiratory phase. These pioneering studies will now permit an analysis of the physiological role of RSA as well as its any potential therapeutic use in cardiac disease.

Topics: Animals; Cardiovascular Diseases; Central Pattern Generators; Heart Rate; Humans; Periodicity; Silicon

Over the past decade, silicon nanowire (SiNW) biosensors have been studied for the detection of biological molecules as highly sensitive, label-free, and electrical tools. Herein we present a comprehensive review about the fabrication of SiNW biosensors and their applications in disease diagnostics. We discuss the detection of important biomarkers related to diseases including cancer, cardiovascular diseases, and infectious diseases. SiNW biosensors hold great promise to realize point-of-care (POC) devices for disease diagnostics with potential for miniaturization and integration.

Topics: Biomarkers, Tumor; Biosensing Techniques; Cardiovascular Diseases; Communicable Diseases; Diagnostic Equipment; Humans; Influenza A Virus, H1N1 Subtype; MicroRNAs; Nanowires; Neoplasms; Silicon; Troponin T

Topics: Cadmium; Calcium; Cardiovascular Diseases; Chromium; Climate; Fluorine; Humans; Iodine; Lithium; Magnesium; Minerals; Silicon; Sodium; United Kingdom; Water Supply

Topics: Animals; Arsenic; Cadmium; Cardiovascular Diseases; Chickens; Chromium; Cobalt; Copper; Dogs; Fluorine; Humans; Manganese; Mice; Nickel; Rabbits; Rats; Selenium; Silicon; Trace Elements; Vanadium; Zinc

We propose a design strategy for affinity-based biosensors using nanowires for sensing and measuring biomarker concentration in biological samples. Such sensors have been shown to have superior properties compared to conventional biosensors in terms of LOD (limit of detection), response time, cost, and size. However, there are several parameters affecting the performance of such devices that must be determined. In order to solve the design problem, we have developed a comprehensive model based on stochastic transport equations that makes it possible to optimize the sensing behavior.

Topics: Biosensing Techniques; Cardiovascular Diseases; Humans; Limit of Detection; Nanowires; Silicon; Stochastic Processes; Troponin

The ability to measure subtle changes in arterial pressure using devices mounted on the skin can be valuable for monitoring vital signs in emergency care, detecting the early onset of cardiovascular disease and continuously assessing health status. Conventional technologies are well suited for use in traditional clinical settings, but cannot be easily adapted for sustained use during daily activities. Here we introduce a conformal device that avoids these limitations. Ultrathin inorganic piezoelectric and semiconductor materials on elastomer substrates enable amplified, low hysteresis measurements of pressure on the skin, with high levels of sensitivity (~0.005 Pa) and fast response times (~0.1 ms). Experimental and theoretical studies reveal enhanced piezoelectric responses in lead zirconate titanate that follow from integration on soft supports as well as engineering behaviours of the associated devices. Calibrated measurements of pressure variations of blood flow in near-surface arteries demonstrate capabilities for measuring radial artery augmentation index and pulse pressure velocity.

Topics: Blood Flow Velocity; Blood Pressure; Calibration; Cardiovascular Diseases; Elastomers; Electrochemistry; Electrodes; Equipment Design; Humans; Lead; Materials Testing; Monitoring, Ambulatory; Monitoring, Physiologic; Nanotechnology; Semiconductors; Signal-To-Noise Ratio; Silicon; Skin; Titanium; Zirconium

A silicon nanosensor technology based on electrical impedance measurements has been developed for the detection of proteins. The nanosensor miniaturizes the high-density, low-volume multiwell plate concept. The scientific core of this technology lies in integrating nanoporous membranes with microfabricated chip platforms. This results in the conversion of individual pores into nanowells of picoliter volume. Monoclonal antibodies were localized and isolated into individual wells. Detection of two cardiac proteomic biomarkers has been demonstrated with this technology. The two proteins, C-reactive protein and NT-pro-brain natriuretic peptide (BNP), are associated with adverse cardiac outcomes in clinical samples when detected in the pg/mL concentration. The formation of the antibody-antigen binding complex occurs in individual wells. The membrane allows for robust separation among individual wells. This technology has the capability to achieve near real-time detection with improved sensitivity at 1 ag/mL for BNP and 1 fg/mL for CRP from human serum.

Topics: C-Reactive Protein; Cardiovascular Diseases; Dose-Response Relationship, Drug; Humans; Immunoassay; Microscopy, Electron, Scanning; Nanopores; Natriuretic Peptide, Brain; Protein Array Analysis; Proteomics; Sensitivity and Specificity; Silicon; Time Factors

In this paper, we present design, fabrication and coupled multifield analysis of hollow out-of-plane silicon microneedles with piezoelectrically actuated microfluidic device for transdermal drug delivery (TDD) system for treatment of cardiovascular or hemodynamic disorders such as hypertension. The mask layout design and fabrication process of silicon microneedles and reservoir involving deep reactive ion etching (DRIE) is first presented. This is followed by actual fabrication of silicon hollow microneedles by a series of combined isotropic and anisotropic etching processes using inductively coupled plasma (ICP) etching technology. Then coupled multifield analysis of a MEMS based piezoelectrically actuated device with integrated silicon microneedles is presented. The coupledfield analysis of hollow silicon microneedle array integrated with piezoelectric micropump has involved structural and fluid field couplings in a sequential structural-fluid analysis on a three-dimensional model of the microfluidic device. The effect of voltage and frequency on silicon membrane deflection and flow rate through the microneedle is investigated in the coupled field analysis using multiple code coupling method. The results of the present study provide valuable benchmark and prediction data to fabricate optimized designs of the silicon hollow microneedle based microfluidic devices for transdermal drug delivery applications.

Topics: Administration, Cutaneous; Cardiotonic Agents; Cardiovascular Diseases; Equipment Design; Equipment Failure Analysis; Humans; Micro-Electrical-Mechanical Systems; Microfluidic Analytical Techniques; Microinjections; Miniaturization; Needles; Silicon

Topics: Alloys; Biomarkers; Cardiovascular Diseases; Dust; Environmental Monitoring; Epidemiological Monitoring; Fibrinogen; Humans; Inhalation Exposure; Iron; Manganese; Occupational Diseases; Particle Size; Risk Factors; Silicon; Sweden

Silicon plays a physiologically essential but mechanistically obscure role in promoting the synthesis of mucopolysaccharides and collagen. In light of reports that increased silicon ingestion impedes cholesterol-induced atherogenesis in rabbits and may be associated epidemiologically with reduced cardiovascular risk, it is reasonable to speculate that supplemental silicon may stimulate endothelial production of heparan sulfate proteoglycans that inhibit intimal hyperplasia.

Topics: Animals; Arteriosclerosis; Cardiovascular Diseases; Cholesterol, Dietary; Diet, Atherogenic; Endothelium, Vascular; Heparan Sulfate Proteoglycans; Heparitin Sulfate; Humans; Models, Cardiovascular; Proteoglycans; Rabbits; Risk Factors; Silicon

Topics: Adult; Cardiovascular Diseases; Chlorine; Environmental Exposure; Female; Humans; Male; Middle Aged; Occupational Diseases; Silicon