Search

Abstract Background A Java™ application is presented, which compares large numbers (n > 100) of raw FTICR mass spectra from patients and controls. Two peptide profile matrices can be produced simultaneously, one with occurrences of peptide masses in samples and another with the intensity of common peak masses in all the measured samples, using the peak- and background intensities of the raw data. In latter way, more significantly differentially expressed peptides are found between groups than just using the presence or absence in samples of common peak masses. The software application is tested by searching angiogenesis related proteins in glioma by comparing laser capture micro dissected- and enzymatic by trypsin digested tissue sections. Results By hierarchical clustering of the presence-absence matrix, it appears that proteins, such as hemoglobin alpha and delta subunit, fibrinogen beta and gamma chain precursor, tubulin specific chaperone A, epidermal fatty acid binding protein, neutrophil gelatinase-associated lipocalin precursor, peptidyl tRNA hydrolase 2 mitochondrial precursor, placenta specific growth hormone, and zinc finger CCHC domain containing protein 13 are significantly different expressed in glioma vessels. The up-regulated proteins in the glioma vessels with respect to the normal vessels determined by the Wilcoxon-Mann-Whitney test on the intensity matrix are vimentin, glial fibrillary acidic protein, serum albumin precursor, annexin A5, alpha cardiac and beta actin, type I cytoskeletal 10 keratin, calcium binding protein p22, and desmin. Peptide masses of calcium binding protein p22, Cdc42 effector protein 3, fibronectin precursor, and myosin-9 are exclusively present in glioma vessels. Some peptide fragments of non-muscular myosin-9 at the C-terminus are strongly up-regulated in the glioma vessels with respect to the normal vessels. Conclusion The less rigorous than in general used commercial propriety software de-isotope algorithm results in more mono-isotopic peptide masses and consequently more proteins. Centroiding of peptide masses takes place by taking the average over more spectra in the profile matrix. Cytoskeleton proteins and proteins involved in the calcium signaling pathway seem to be most up-regulated in glioma vessels. The finding that peptides at the C-terminus of myosin-9 are up-regulated could be ascribed to splicing or fragmentation by proteases.

Intracortical brain-computer interfaces offer superior spatial and temporal resolutions, but face challenges as the increasing number of recording channels introduces high amounts of data to be transferred. This requires power-hungry data serialization and telemetry, leading to potential tissue damage risks. To address this challenge, this paper introduces an event-based neural compressive telemetry (NCT) consisting of 8 channel-rotating Δ-ADCs, an event-driven serializer supporting a proposed ternary address event representation protocol, and an event-based LVDS driver. Leveraging a high sparsity of extracellular spikes and high spatial correlation of the high-density recordings, the proposed NCT achieves a compression ratio of >11.4×, while consumes only 1 µW per channel, which is 127× more efficient than state of the art. The NCT well preserves the spike waveform fidelity, and has a low normalized RMS error <23% even with a spike amplitude down to only 31 µV.

Neuromorphic processors promise low-latency and energy-efficient processing by adopting novel brain-inspired design methodologies. Yet, current neuromorphic solutions still struggle to rival conventional deep learning accelerators' performance and area efficiency in practical applications. Event-driven data-flow processing and near/in-memory computing are the two dominant design trends of neuromorphic processors. However, there remain challenges in reducing the overhead of event-driven processing and increasing the mapping efficiency of near/in-memory computing, which directly impacts the performance and area efficiency. In this work, we discuss these challenges and present our exploration of optimizing event-based neural network inference on SENECA, a scalable and flexible neuromorphic architecture. To address the overhead of event-driven processing, we perform comprehensive design space exploration and propose spike-grouping to reduce the total energy and latency. Furthermore, we introduce the event-driven depth-first convolution to increase area efficiency and latency in convolutional neural networks (CNNs) on the neuromorphic processor. We benchmarked our optimized solution on keyword spotting, sensor fusion, digit recognition and high resolution object detection tasks. Compared with other state-of-the-art large-scale neuromorphic processors, our proposed optimizations result in a 6× to 300× improvement in energy efficiency, a 3× to 15× improvement in latency, and a 3× to 100× improvement in area efficiency. Our optimizations for event-based neural networks can be potentially generalized to a wide range of event-based neuromorphic processors., Competing Interests: YX, KS, G-JS, AD, SW, RM, PN, CA, PM, PD, ST, MK, KV, MS, GT, and AY were employed by IMEC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xu, Shidqi, van Schaik, Bilgic, Dobrita, Wang, Meijer, Nembhani, Arjmand, Martinello, Gebregiorgis, Hamdioui, Detterer, Traferro, Konijnenburg, Vadivel, Sifalakis, Tang and Yousefzadeh.)

Neuromorphic processors aim to emulate the biological principles of the brain to achieve high efficiency with low power consumption. However, the lack of flexibility in most neuromorphic architecture designs results in significant performance loss and inefficient memory usage when mapping various neural network algorithms. This paper proposes SENECA, a digital neuromorphic architecture that balances the trade-offs between flexibility and efficiency using a hierarchical-controlling system. A SENECA core contains two controllers, a flexible controller (RISC-V) and an optimized controller (Loop Buffer). This flexible computational pipeline allows for deploying efficient mapping for various neural networks, on-device learning, and pre-post processing algorithms. The hierarchical-controlling system introduced in SENECA makes it one of the most efficient neuromorphic processors, along with a higher level of programmability. This paper discusses the trade-offs in digital neuromorphic processor design, explains the SENECA architecture, and provides detailed experimental results when deploying various algorithms on the SENECA platform. The experimental results show that the proposed architecture improves energy and area efficiency and illustrates the effect of various trade-offs in algorithm design. A SENECA core consumes 0.47 mm 2 when synthesized in the GF-22 nm technology node and consumes around 2.8 pJ per synaptic operation. SENECA architecture scales up by connecting many cores with a network-on-chip. The SENECA platform and the tools used in this project are freely available for academic research upon request., Competing Interests: All authors were employed by Imec., (Copyright © 2023 Tang, Vadivel, Xu, Bilgic, Shidqi, Detterer, Traferro, Konijnenburg, Sifalakis, van Schaik and Yousefzadeh.)

This paper presents a low power, high dynamic range (DR), light-to-digital converter (LDC) for wearable chest photoplethysmogram (PPG) applications. The proposed LDC utilizes a novel 2 nd -order noise-shaping slope architecture, directly converting the photocurrent to a digital code. This LDC applies a high-resolution dual-slope quantizer for data conversion. An auxiliary noise shaping loop is used to shape the residual quantization noise. Moreover, a DC compensation loop is implemented to cancel the PPG signal's DC component, thus further boosting the DR. The prototype is fabricated with 0.18 μm standard CMOS and characterized experimentally. The LDC consumes 28 μW per readout channel while achieving a maximum 134 dB DR. The LDC is also validated with on-body chest PPG measurement.

Research on heart rate (HR) estimation using wrist-worn photoplethysmography (PPG) sensors have progressed rapidly owing to the prominence of commercial sensing modules, used widely for lifestyle monitoring. Reported methodologies have been fairly successful in mitigating the effect of motion artifacts (MA) in ambulatory environment for HR estimation. Recently, a learning framework, CorNET, employing two-layer convolution neural networks (CNN) and two-layer long short-term network (LSTM) was successfully reported for estimating HR from MA-induced PPG signals. However, such a network topology with large number of parameters presents a challenge, towards low-complexity hardware implementation aimed at on-node processing. In this paper, we demonstrate a fully binarized network (bCorNET) topology and its corresponding algorithm-to-architecture mapping and energy-efficient implementation for HR estimation. The proposed framework achieves a MAE of 6.67 ± 5.49 bpm when evaluated on 22 IEEE SPC subjects. The design, synthesized with ST65 nm technology library achieving 3 GOPS @ 1 MHz, consumes 56.1 μJ per window with occupied 1634K NAND2 equivalent cell area and had a latency of 32 ms when estimating HR every 2 s from PPG signals.

This paper presents a low power, high dynamic range (DR), reconfigurable light-to-digital converter (LDC) for photoplethysmogram (PPG), and near-infrared spectroscopy (NIRS) sensor readouts. The proposed LDC utilizes a current integration and a charge counting operation to directly convert the photocurrent to a digital code, reducing the noise contributors in the system. This LDC consists of a latched comparator, a low-noise current reference, a counter, and a multi-function integrator, which is used in both signal amplification and charge counting based data quantization. Furthermore, a current DAC is used to further increase the DR by canceling the baseline current. The LDC together with LED drivers and auxiliary digital circuitry are implemented in a standard 0.18 μm CMOS process and characterized experimentally. The LDC and LED drivers consume a total power of 196 μW while achieving a maximum 119 dB DR. The charge counting clock, and the pulse repetition frequency of the LED driver can be reconfigured, providing a wide range of power-resolution trade-off. At a minimum power consumption of 87 μW, the LDC still achieves 95 dB DR. The LDC is also validated with on-body PPG and NIRS measurement by using a photodiode (PD) and a silicon photomultiplier (SIPM), respectively.

An all-in-one battery powered low-power SoC for measuring multiple vital signs with wearables is proposed. All functionality needed in a typical wearable use case scenario, including dedicated readouts, power management circuitry, digital signal processing and wireless communication (BLE) is integrated in a single die. This high level of integration allows an unprecedented level of miniaturization leading to smaller component count which reduces cost and improves comfort and signal integrity. The SoC includes an ECG, Bio-Impedance and a fully differential PPG readout and can interface with external sensors (like an IMU). In a typical application scenario where all sensor readouts are enabled and key features (like heart rate) are calculated on the chip and streamed over the radio, the SoC consumes only 769 μW from the regulated 1.2 V supply.

Advancements in wireless sensor networks (WSN) technology and miniaturization of wearable sensors have enabled long-term continuous pervasive biomedical signal monitoring. Wrist-worn photoplethysmography (PPG) sensors have gained popularity given their form factor. However the signal quality suffers due to motion artifacts when used in ambulatory settings, making vital parameter estimation a challenging task. In this paper, we present a novel deep learning framework, BioTranslator, for computing the instantaneous heart rate (IHR), using wrist-worn PPG signals collected during physical activity. Using one-dimensional Convolution-Deconvolution Network, we translate a single channel PPG signal to an electrocardiogram(ECG)-like time series signal, from which relevant R-peak information can be inferred enabling IHR measures. The proposed network configuration was evaluated on 12 subjects of the TROIKA dataset, involved in physical activity. The proposed network identifies 92.8% of R-peaks, besides achieving a mean absolute error of 51±6.3ms with respect to reference ECG-derived IHR.

Advancements in wireless sensor network technologies have enabled the proliferation of miniaturized body-worn sensors, capable of long-term pervasive biomedical signal monitoring. Remote cardiovascular monitoring has been one of the beneficiaries of this development, resulting in non-invasive, photoplethysmography (PPG) sensors being used in ambulatory settings. Wrist-worn PPG, although a popular alternative to electrocardiogram, suffers from motion artifacts inherent in daily life. Hence, in this paper, we present a novel deep learning framework (CorNET) to efficiently estimate heart rate (HR) information and perform biometric identification (BId) using only a wrist-worn, single-channel PPG signal collected in ambulant environment. We have formulated a completely personalized data-driven approach, using a four-layer deep neural network. Two convolution neural network layers are used in conjunction with two long short-term memory layers, followed by a dense output layer for modeling the temporal sequence inherent within the pulsatile signal representative of cardiac activity. The final dense layer is customized with respect to the application, functioning as: regression layer-having a single neuron to predict HR; classification layer-two neurons that identify a subject among a group. The proposed network was evaluated on the TROIKA dataset having 22 PPG records collected during various physical activities. We achieve a mean absolute error of 1.47 ± 3.37 beats per minute for HR estimation and an average accuracy of 96% for BId on 20 subjects. CorNET was further evaluated successfully in an ambulant use-case scenario with custom sensors for two subjects.

This paper presents a sub-mW ASIC for multimodal brain monitoring. The ASIC is co-integrated with electrode(s) and optodes (i.e., optical source and detector) as an active sensor to measure electroencephalography (EEG), bio-impedance (BioZ), and near-infrared spectroscopy (NIRS) on scalp. The target is to build a wearable EEG-NIRS headset for low-cost functional brain imaging. The proposed NIRS readout utilizes the near-infrared light to measure the pulse oximetry and blood oxygen saturation (SpO 2 ). While traditional photodiodes are supported, the readout also allows the use of silicon photomultipliers (SiPMs) as optical detectors. The SiPM improves optical sensitivity while significantly reducing the average power of two LEDs to 150 μW. On circuit level, a SAR-based calibration compensates maximum 40 μA current from ambient light, while digital DC-servo loops reduces the baseline static SiPM current up to 400 μA, leading to an overall dynamic range of 87 dB. The EEG readout exhibits 720 MΩ input impedance at 50 Hz. The BioZ readout has 3 mΩ/√(Hz) impedance sensitivity by employing dynamic circuit techniques. When EEG, BioZ, and NIRS are enabled at the same time, one ASIC consumes 665 μW including the power of LEDs.

This paper presents a 1.2 V 36 μW reconfigurable analog front-end (R-AFE) as a general-purpose low-cost IC for multiple-mode biomedical signals acquisition. The R-AFE efficiently reuses a reconfigurable preamplifier, a current generator (CG), and a mixed signal processing unit, having an area of 1.1 mm2 per R-AFE while supporting five acquisition modes to record different forms of cardiovascular and respiratory signals. The R-AFE can interface with voltage-, current-, impedance-, and light-sensors and hence can measure electrocardiography (ECG), bio-impedance (BioZ), photoplethysmogram (PPG), galvanic skin response (GSR), and general-purpose analog signals. Thanks to the chopper preamplifier and the low-noise CG utilizing dynamic element matching, the R-AFE mitigates ${\text{1}}\text{/}f$ noise from both the preamplifier and the CG for improved measurement sensitivity. The IC achieves competitive performance compared to the state-of-the-art dedicated readout ICs of ECG, BioZ, GSR, and PPG, but with approximately 1.4×-5.3× smaller chip area per channel.

High-resolution Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry imaging enables the spatial mapping and identification of biomolecules from complex surfaces. The need for long time-domain transients, and thus large raw file sizes, results in a large amount of raw data ("big data") that must be processed efficiently and rapidly. This can be compounded by large-area imaging and/or high spatial resolution imaging. For FT-ICR, data processing and data reduction must not compromise the high mass resolution afforded by the mass spectrometer. The continuous mode "Mosaic Datacube" approach allows high mass resolution visualization (0.001 Da) of mass spectrometry imaging data, but requires additional processing as compared to feature-based processing. We describe the use of distributed computing for processing of FT-ICR MS imaging datasets with generation of continuous mode Mosaic Datacubes for high mass resolution visualization. An eight-fold improvement in processing time is demonstrated using a Dutch nationally available cloud service.

This paper describes a mixed-signal ECG System-on-Chip (SoC) that is capable of implementing configurable functionality with low-power consumption for portable ECG monitoring applications. A low-voltage and high performance analog front-end extracts 3-channel ECG signals and single channel electrode-tissue-impedance (ETI) measurement with high signal quality. This can be used to evaluate the quality of the ECG measurement and to filter motion artifacts. A custom digital signal processor consisting of 4-way SIMD processor provides the configurability and advanced functionality like motion artifact removal and R peak detection. A built-in 12-bit analog-to-digital converter (ADC) is capable of adaptive sampling achieving a compression ratio of up to 7, and loop buffer integration reduces the power consumption for on-chip memory access. The SoC is implemented in 0.18 μm CMOS process and consumes 32 μ W from a 1.2 V while heart beat detection application is running, and integrated in a wireless ECG monitoring system with Bluetooth protocol. Thanks to the ECG SoC, the overall system power consumption can be reduced significantly.

Mass spectrometry imaging by Fourier transform ion cyclotron resonance (FT-ICR) yields hundreds of unique peaks, many of which cannot be resolved by lower performance mass spectrometers. The high mass accuracy and high mass resolving power allow confident identification of small molecules and lipids directly from biological tissue sections. Here, calibration strategies for FT-ICR MS imaging were investigated. Sub-parts-per-million mass accuracy is demonstrated over an entire tissue section. Ion abundance fluctuations are corrected by addition of total and relative ion abundances for a root-mean-square error of 0.158 ppm on 16,764 peaks. A new approach for visualization of FT-ICR MS imaging data at high resolution is presented. The "Mosaic Datacube" provides a flexible means to visualize the entire mass range at a mass spectral bin width of 0.001 Da. The high resolution Mosaic Datacube resolves spectral features not visible at lower bin widths, while retaining the high mass accuracy from the calibration methods discussed.

This paper presents a voltage-scalable digital signal processing system designed for the use in a wireless sensor node (WSN) for ambulatory monitoring of biomedical signals. To fulfill the requirements of ambulatory monitoring, power consumption, which directly translates to the WSN battery lifetime and size, must be kept as low as possible. The proposed processing platform is an event-driven system with resources to run applications with different degrees of complexity in an energy-aware way. The architecture uses effective system partitioning to enable duty cycling, single instruction multiple data (SIMD) instructions, power gating, voltage scaling, multiple clock domains, multiple voltage domains, and extensive clock gating. It provides an alternative processing platform where the power and performance can be scaled to adapt to the application need. A case study on a continuous wavelet transform (CWT)-based heart-beat detection shows that the platform not only preserves the sensitivity and positive predictivity of the algorithm but also achieves the lowest energy/sample for ElectroCardioGram (ECG) heart-beat detection publicly reported today.

This paper describes an ultra-low power (ULP) single chip transceiver for wireless body area network (WBAN) applications. It supports on-off keying (OOK) modulation, and it operates in the 2.36-2.4 GHz medical BAN and 2.4-2.485 GHz ISM bands. It is implemented in 90 nm CMOS technology. The direct modulated transmitter transmits OOK signal with 0 dBm peak power, and it consumes 2.59 mW with 50% OOK. The transmitter front-end supports up to 10 Mbps. The transmitter digital baseband enables digital pulse-shaping to improve spectrum efficiency. The super-regenerative receiver front-end supports up to 5 Mbps with -75 dBm sensitivity. Including the digital part, the receiver consumes 715 μW at 1 Mbps data rate, oversampled at 3 MHz. At the system level the transceiver achieves PER=10 (-2) at 25 meters line of site with 62.5 kbps data rate and 288 bits packet size. The transceiver is integrated in an electrocardiogram (ECG) necklace to monitor the heart's electrical property.

In this paper a novel workflow-based data acquisition and control system for Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) is presented that facilitates a fast on-the-fly decision-making process for a wide variety of data-dependent experiments. Several new workflow implementations demonstrate the flexibility and benefit of this approach for rapid dynamic experimental design on a chromatographic timescale. The different sequence, evaluation, decision and monitoring modules are described using a selected set of examples. During a tandem liquid chromatography (LC)/FTICR-MS experiment the system is used to dynamically switch between various dissociation techniques such as electron capture dissociation (ECD) and sustained off-resonance irradiation (SORI) depending on the charge state of a tryptic peptide peak. The use of this workflow-based system for imaging FTICR-MS using a desorption electrospray ionization (DESI) source demonstrates the possibility of external control of the workflow by feedback from an imaging sample stage.