A surface-functionalized whole blood-based dielectric microsensor for assessment of clot firmness in a fibrinolytic environment.

Accurate assessment of fibrin clot stability can predict bleeding risk in coagulopathic conditions such as thrombocytopenia and hypofibrinogenemia. Hyperfibrinolysis - a clinical phenotype characterized by an accelerated breakdown of the fibrin clot - makes such assessments challenging by obfuscating the effect of hemostatic components including platelets or fibrinogen on clot stability. In this work, we present a biofunctionalized, microfluidic, label-free, electronic biosensor to elicit unique, specific, and differential responses from the multifactorial processes of blood coagulation and fibrinolysis ex vivo.

Δ BP-Net: Monitoring "Changes" in Blood Pressure Using PPG with Self-contrastive Masking.

Estimating blood pressure (BP) values from physiological signals (e.g., photoplethysmogram (PPG)) using deep learning models has recently received increased attention, yet challenges remain in terms of models' generalizability.

A miniaturized wash-free microfluidic assay for electrical impedance-based assessment of red blood cell-mediated microvascular occlusion.

The production of HbS - an abnormal hemoglobin (Hb) - in sickle cell disease (SCD) results in poorly deformable red blood cells (RBCs) that are prone to microcapillary occlusion, causing tissue ischemia and organ damage. Novel treatments, including gene therapy, may reduce SCD morbidity, but methods to functionally evaluate RBCs remain limited. Previously, we presented the microfluidic impedance red cell assay (MIRCA) for rapid assessment of RBC deformability, employing electrical impedance-based readout to measure RBC occlusion of progressively narrowing micropillar openings.

Demographic Information Fusion Using Attentive Pooling In CNN-GRU Model For Systolic Blood Pressure Estimation.

Fusing demographic information into deep learning models has become of interest in recent end-to-end cuff-less blood pressure (BP) estimation studies in order to achieve improved performance. Conventionally, the demographic feature vector is concatenated with the pooled embedding vector. Here, using an attention-based convolutional neural network-gated recurrent unit (CNN-GRU), we present a new approach and fuse the demographic information into the attentive pooling module.

A Multichannel Portable Platform With Embedded Thermal Management for Miniaturized Dielectric Blood Coagulometry.

This article presents a standalone, multichannel, miniaturized impedance analyzer (MIA) system for dielectric blood coagulometry measurements with a microfluidic sensor termed ClotChip. The system incorporates a front-end interface board for 4-channel impedance measurements at an excitation frequency of 1 MHz, an integrated resistive heater formed by a pair of printed-circuit board (PCB) traces to keep the blood sample near a physiologic temperature of 37 °C, a software-defined instrument module for signal generation and data acquisition, and a Raspberry Pi-based embedded computer with 7-inch touchscreen display for signal processing and user interface. When measuring fixed test impedances across all four channels, the MIA system exhibits an excellent agreement with a benchtop impedance analyzer, with rms errors of ≤0.

Bioelectronic Sensor Nodes for the Internet of Bodies.

Energy-efficient sensing with physically secure communication for biosensors on, around, and within the human body is a major area of research for the development of low-cost health care devices, enabling continuous monitoring and/or secure perpetual operation. When used as a network of nodes, these devices form the Internet of Bodies, which poses challenges including stringent resource constraints, simultaneous sensing and communication, and security vulnerabilities. Another major challenge is to find an efficient on-body energy-harvesting method to support the sensing, communication, and security submodules.

PulseDB: A large, cleaned dataset based on MIMIC-III and VitalDB for benchmarking cuff-less blood pressure estimation methods.

There has been a growing interest in developing cuff-less blood pressure (BP) estimation methods to enable continuous BP monitoring from electrocardiogram (ECG) and/or photoplethysmogram (PPG) signals. The majority of these methods have been evaluated using publicly-available datasets, however, there exist significant discrepancies across studies with respect to the size, the number of subjects, and the applied pre-processing steps for the data that is eventually used for training and testing the models. Such differences make conducting performance comparison across models largely unfair, and mask the generalization capability of various BP estimation methods.

Broad Therapeutic Time Window for Driving Motor Recovery After TBI Using Activity-Dependent Stimulation.

Background: After an acquired injury to the motor cortex, the ability to generate skilled movements is impaired, leading to long-term motor impairment and disability. While rehabilitative therapy can improve outcomes in some individuals, there are no treatments currently available that are able to fully restore lost function.

Objective: We previously used activity-dependent stimulation (ADS), initiated immediately after an injury, to drive motor recovery.

Design and Optimization of Capacitive Links for Wireless Power Transfer to Biomedical Implants.

This paper provides a comprehensive overview of capacitive wireless power transfer (C-WPT) links for biomedical implants, and proposes an algorithmic approach to optimize their design for a theoretically feasible desired power transmission efficiency (PTE). Two C-WPT links, one involving external inductors for parasitic capacitance cancellation, and another without external inductors are presented. An accurate electrical model has been presented for both cases considering the finite conductivity of the body tissue and fringe fields emanated from the metallic plates.

The Effects of Filtering PPG Signal on Pulse Arrival Time-Systolic Blood Pressure Correlation.

Pulse arrival time (PAT), evaluated from electro-cardiogram (ECG) and photoplethysmogram (PPG) signals, has been widely used for cuff-less blood pressure (BP) estimation due to its high correlation with BP. However, the question of whether filtering the PPG signal impacts the extracted PAT values and consequently, the correlation between PAT and BP, has not been investigated before. In this paper, using data from 18 subjects, changes in the PAT values, and in the subject-specific PAT-systolic BP (SBP) correlation caused by filtering the PPG signal with variable cutoff frequencies in the range of 2 to 15 Hz are studied.

Assessment of fibrinolytic status in whole blood using a dielectric coagulometry microsensor.

Rapid assessment of the fibrinolytic status in whole blood at the point-of-care/point-of-injury (POC/POI) is clinically important to guide timely management of uncontrolled bleeding in patients suffering from hyperfibrinolysis after a traumatic injury. In this work, we present a three-dimensional, parallel-plate, capacitive sensor - termed ClotChip - that measures the temporal variation in the real part of blood dielectric permittivity at 1 MHz as the sample undergoes coagulation within a microfluidic channel with <10 μL of total volume. The ClotChip sensor features two distinct readout parameters, namely, lysis time (LT) and maximum lysis rate (MLR) that are shown to be sensitive to the fibrinolytic status in whole blood.

PulseLab: An Integrated and Expandable Toolbox for Pulse Wave Velocity-based Blood Pressure Estimation.

In this paper, we introduce PulseLab, a comprehensive MATLAB toolbox that enables estimating the blood pressure (BP) from electrocardiogram (ECG) and photoplethysmogram (PPG) signals using pulse wave velocity (PWV)-based models. This universal framework consists of 6 sequential modules, covering end-to-end procedures that are needed for estimating BP from raw PPG/ECG data. These modules are "dataset formation", "signal pre-processing", "segmentation", "characteristic-points detection", "pulse transit time (PTT)/ pulse arrival time (PAT) calculation", and "model validation".

Cuff-Less Blood Pressure Estimation via Small Convolutional Neural Networks.

Deep learning-based cuff-less blood pressure (BP) estimation methods have recently gained increased attention as they can provide accurate BP estimation with only one physiological signal as input. In this paper, we present a simple and effective method for cuff-less BP estimation by training a small-scale convolutional neural network (CNN), modified from LeNet-5, with images created from short segments of the photoplethysmogram (PPG) signal via visibility graph (VG). Results show that the trained modified LeNet-5 model achieves an error performance of 0.

Cuff-Less Blood Pressure Estimation From Photoplethysmography via Visibility Graph and Transfer Learning.

This paper presents a new solution that enables the use of transfer learning for cuff-less blood pressure (BP) monitoring via short duration of photoplethysmogram (PPG). The proposed method estimates BP with low computational budget by 1) creating images from segments of PPG via visibility graph (VG), hence, preserving the temporal information of the PPG waveform, 2) using pre-trained deep convolutional neural network (CNN) to extract feature vectors from VG images, and 3) solving for the weights and bias between the feature vectors and the reference BPs with ridge regression. Using the University of California Irvine (UCI) database consisting of 348 records, the proposed method achieves a best error performance of 0.

On the Non-idealities of a Capacitive Link for Wireless Power Transfer to Biomedical Implants.

This paper studies the performance of a resonant capacitive wireless power transfer (C-WPT) link for biomedical implants in the presence of non-idealities. The study emphasizes on finding an accurate electrical model of a practical C-WPT link, which can be used to investigate the performance of the link under different practical/non-ideal scenarios. A sound knowledge about these non-idealities is crucial for device optimization.

Microfluidic electrical impedance assessment of red blood cell-mediated microvascular occlusion.

Alterations in the deformability of red blood cells (RBCs), occurring in hemolytic blood disorders such as sickle cell disease (SCD), contribute to vaso-occlusion and disease pathophysiology. There are few functional in vitro assays for standardized assessment of RBC-mediated microvascular occlusion. Here, we present the design, fabrication, and clinical testing of the Microfluidic Impedance Red Cell Assay (MIRCA) with embedded capillary network-based micropillar arrays and integrated electrical impedance measurement electrodes to address this need.

A Dual-Output Single-Stage Regulating Rectifier With PWM and Dual-Mode PFM Control for Wireless Powering of Biomedical Implants.

This paper presents a reconfigurable, dual-output, regulating rectifier featuring pulse width modulation (PWM) and dual-mode pulse frequency modulation (PFM) control schemes for single-stage ac-to-dc conversion to provide two independently regulated supply voltages (each in 1.5-3 V) from an input ac voltage. The dual-mode PFM controllers feature event-driven regulation as well as frequency division.

A 280 μW, 108 dB DR PPG-Readout IC With Reconfigurable, 2nd-Order, Incremental ΔΣM Front-End for Direct Light-to-Digital Conversion.

This paper reports on a low-power readout IC (ROIC) for high-fidelity recording of the photoplethysmogram (PPG) signal. The system comprises a highly reconfigurable, continuous-time, second-order, incremental delta-sigma modulator (I-ΔΣM) as a light-to-digital converter (LDC), a 2-channel 10b light-emitting diode (LED) driver, and an integrated digital signal processing (DSP) unit. The LDC operation in intermittent conversion phases coupled with digital assistance by the DSP unit allow signal-aware, on-the-fly cancellation of the dc and ambient light-induced components of the photodiode current for more efficient use of the full-scale input range for recording of the small-amplitude, ac, PPG signal.

Monitoring DOACs with a Novel Dielectric Microsensor: A Clinical Study.

Background:  There are acute settings where assessing the anticoagulant effect of direct oral anticoagulants (DOACs) can be useful. Due to variability among routine coagulation tests, there is an unmet need for an assay that detects DOAC effects within minutes in the laboratory or at the point of care.

Methods:  We developed a novel dielectric microsensor, termed ClotChip, and previously showed that the time to reach peak permittivity ( ) is a sensitive parameter of coagulation function.

A novel, point-of-care, whole-blood assay utilizing dielectric spectroscopy is sensitive to coagulation factor replacement therapy in haemophilia A patients.

Background: Reliable monitoring of coagulation factor replacement therapy in patients with severe haemophilia, especially those with inhibitors, is an unmet clinical need. While useful, global assays, eg thromboelastography (TEG), rotational thromboelastometry (ROTEM) and thrombin generation assay (TGA), are cumbersome to use and not widely available.

Objective: To assess the utility of a novel, point-of-care, dielectric microsensor - ClotChip - to monitor coagulation factor replacement therapy in patients with haemophilia A, with and without inhibitors.

Modeling and Characterization of Capacitive Elements With Tissue as Dielectric Material for Wireless Powering of Neural Implants.

This paper reports on the modeling and characterization of capacitive elements with tissue as the dielectric material, representing the core building block of a capacitive link for wireless power transfer to neural implants. Each capacitive element consists of two parallel plates that are aligned around the tissue layer and incorporate a grounded, guarded, capacitive pad to mitigate the adverse effect of stray capacitances and shield the plates from external interfering electric fields. The plates are also coated with a biocompatible, insulating, coating layer on the inner side of each plate in contact with the tissue.

A Brain-Spinal Interface (BSI) System-on-Chip (SoC) for Closed-Loop Cortically-Controlled Intraspinal Microstimulation.

This paper reports on a fully miniaturized brain-spinal interface (BSI) system for closed-loop cortically-controlled intraspinal microstimulation (ISMS). Fabricated in AMS 0.35μm two-poly four-metal complementary metal-oxide-semiconductor (CMOS) technology, this system-on-chip (SoC) measures ~ 3.

C-FSCV: Compressive Fast-Scan Cyclic Voltammetry for Brain Dopamine Recording.

This paper presents a novel compressive sensing framework for recording brain dopamine levels with fast-scan cyclic voltammetry (FSCV) at a carbon-fiber microelectrode. Termed compressive FSCV (C-FSCV), this approach compressively samples the measured total current in each FSCV scan and performs basic FSCV processing steps, e.g.

ClotChip: A Microfluidic Dielectric Sensor for Point-of-Care Assessment of Hemostasis.

This paper describes the design, fabrication, and testing of a microfluidic sensor for dielectric spectroscopy of human whole blood during coagulation. The sensor, termed ClotChip, employs a three-dimensional, parallel-plate, capacitive sensing structure with a floating electrode integrated into a microfluidic channel. Interfaced with an impedance analyzer, the ClotChip measures the complex relative dielectric permittivity, ϵ , of human whole blood in the frequency range of 40 Hz to 100 MHz.

A PMMA microfluidic dielectric sensor for blood coagulation monitoring at the point-of-care.

This paper describes the design and construct of a fully biocompatible, microfluidic, dielectric sensor targeted at monitoring human whole blood coagulation at the point-of-care (POC). The sensor assembly procedure involves using sputtered electrodes in a microfluidic channel with a physiologically relevant height of 50μm to create a three-dimensional (3D), parallel-plate, capacitive sensing area. The sensor is constructed with biocompatible materials of polymethyl methacrylate (PMMA) for the substrate and titanium nitride (TiN) for the sensing and floating electrodes.