A handheld high-sensitivity micro-NMR CMOS platform with B-field stabilization for multi-type biological/chemical assays

We report a micro-nuclear magnetic resonance (NMR) system compatible with multi-type biological/chemical lab-on-a-chip assays. Unified in a handheld scale (dimension: 14 x 6 x 11 cm³, weight: 1.4 kg), the system is capable to detect<100 pM of Enterococcus faecalis derived DNA from a 2.5 μL sample. The key components are a portable magnet (0.46 T, 1.25 kg) for nucleus magnetization, a system PCB for I/O interface, an FPGA for system control, a current driver for trimming the magnetic (B) field, and a silicon chip fabricated in 0.18 μm CMOS. The latter, integrated with a current-mode vertical Hall sensor and a low-noise readout circuit, facilitates closed-loop B-field stabilization (2 mT → 0.15 mT), which otherwise fluctuates with temperature or sample displacement. Together with a dynamic-B-field transceiver with a planar coil for micro-NMR assay and thermal control, the system demonstrates: 1) selective biological target pinpointing; 2) protein state analysis; and 3) solvent-polymer dynamics, suitable for healthcare, food and colloidal applications, respectively. Compared to a commercial NMR-assay product (Bruker mq-20), this platform greatly reduces the sample consumption (120x), hardware volume (175x), and weight (96x)

Photovoltaic power harvesting technologies in biomedical implantable devices considering the optimal location

here are still many challenges in effectively harvesting and generating power for implantable medical devices. Most of today's research focuses on finding ways to harvest energy from the human body to avoid the use of batteries, which require surgical replacement. For example, current energy harvesters rely on piezoelectricity, thermoelectricity and solar electricity to drive the implantable device. However, the majority of these energy harvesting techniques suffer from a variety of limitations such as low power output, large size or poor efficiency. Due to their high efficiency, we focus our attention on solar photovoltaic cells. We demonstrate the tissue absorption losses severely influence their performance. We predict the performance of these cells using simulation through the verified experimental data. Our results show that our model can obtain 17.20% efficiency and 0.675 V open-circuit voltage in one sun condition. In addition, our device can also harvest up to 15 mW/ cm2 in dermis and 11.84 mW/ cm2 in hypodermis by using 100 mW/ cm2 light source at 800 nm and 850 nm, respectively. We propose implanting our device in hypodermis to obtain a stable power output

An Implantable Photovoltaic Energy Harvesting System With Skin Optical Analysis

Medical implantable devices can use photovoltaic (PV) energy harvesting to extend battery life span and increase their performance. The power conditioning and management circuitry is essential not only to regulate the voltage requirements of the load but also optimize the output power of PV cells. However, the optical losses due to the skin and the device characteristics of the PV cells are rarely analyzed before chip fabrication. This inevitably leads to sub-optimal system performance in in-vitro or in-vivo tests owing to the varying PV output characteristics. To address this problem, we use the finite-element-method (FEM) to analyze the optical and physical performance of the PV cell under the skin, and then export the model into the p-spice simulator for circuit-level implementation. We further demonstrate a 1:2 cross-coupled DC-DC converter using pulse density modulation for load regulation control to meet the loading requirement. In this work, the PV cell can achieve an 18% of efficiency, and the power conditioning circuit can provide an 84% of end-to-end efficiency

IEEE Access special section editorial: energy harvesting technologies for wearable and implantable devices

Implantable and wearable electronic devices can improve the quality of life as well as the life expectancy of many chronically ill patients, provided that certain biological signs can be accurately monitored. Thanks to advancements in packaging and nanofabrication, it is now possible to embed various microelectronic and micromechanical sensors such as gyroscopes, accelerometers, and image sensors into a small area on a flexible substrate and at a relatively low cost. Furthermore, these devices have been integrated with wireless communication technologies to enable the transmission of both signals and energy. However, to ensure that these devices can truly improve a patient’s quality of life, new preventative, diagnostic, and therapeutic devices that can provide hassle-free, long-term, continuous monitoring will need to be developed, which must rely on novel energy harvesting solutions that are non-obstructive to its wearer. So far, research in the field has focused on materials, new processing techniques, and one-off devices. However, existing progress is not sufficient for future electronic devices to be useful in any new application, and a great demand exists toward scaling up the research toward circuits and systems. Few interesting developments in this direction indicate that special attention should be given toward the design, simulation, and modeling of energy harvesting techniques while keeping system integration and power management in consideration

Self-powered implantable CMOS photovoltaic cell with 18.6% efficiency

Harvesters for implantable medical applications need to generate enough energy to power their loads, but their efficiency is reduced when implanted under the tissue. Conventional photovoltaic (PV) cell harvesters made with CMOS technology stack cells in series, which raises output voltage but lowers power conversion efficiency. In addition, it is difficult to assess harvester performance prior to fabrication. To address these challenges, we developed a novel parallel PV cell configuration that fully utilizes all triple-well diodes and responds efficiently to near-infrared light. Using an optimized structure, the PV cells were fabricated through standard TSMC 65-nm CMOS technology, achieving an efficiency of 18.6%, open circuit voltage of 0.45 V, and short circuit current of 1.9 mA cm −2 . These results confirm the ability of the device to generate sufficient energy even when implanted beneath the tissue. Multiphysics finite element modeling (FEM) was used to optimize the stacking structure of the CMOS PV cell, and experimental results showed a successfully delivered power density of 1.2 mW cm −2 (single cell 1.04 mm 2 ) when placed 2 mm below porcine skin. Different array configurations of six PV cells were also experimentally studied using external wire switching, demonstrating the flexibility of the PV array in delivering different output energy for various implantable devices

Simulation of crystalline silicon photovoltaic cells for wearable applications

Advancements in the semiconductor industry have enabled wearable devices to be used for a wide range of applications, including personalised healthcare. Novel energy harvesting technologies are therefore necessary to ensure that these devices can be used without interruption. Crystalline silicon photovoltaic cells provide high energy density to electronic loads. However, the optimization of these cells is a complex task since the optical performance is coupled to the surroundings, and the electrical performance is influenced by the intrinsic PV characteristics and parasitic losses.Without doubt, accurate simulation tools can provide the necessary insight to PV cell performance before device fabrication. However, the majority of these tools require expensive licensing fees. Thus, the aim of this article is to review the range of non-commercial PV simulation tools that can be used for wearable applications. We provide a detailed procedure for device modelling and we compare the performance of these tools with previously published experimental data, as well as commercial software. According to our findings, non-commercial 3D simulation tools such as PC3D provide accurate results, with only a relative error of ≈2.2% in Jsc after setting off the difference in geometrical modelling due to the software limit

Self-powered implantable medical devices: photovoltaic energy harvesting review

Implantable technologies are becoming more widespread for biomedical applications that include physical identification, health diagnosis, monitoring, recording, and treatment of human physiological traits. However, energy harvesting and power generation beneath the human tissue are still a major challenge. In this regard, self‐powered implantable devices that scavenge energy from the human body are attractive for long‐term monitoring of human physiological traits. Thanks to advancements in material science and nanotechnology, energy harvesting techniques that rely on piezoelectricity, thermoelectricity, biofuel, and radio frequency power transfer are emerging. However, all these techniques suffer from limitations that include low power output, bulky size, or low efficiency. Photovoltaic (PV) energy conversion is one of the most promising candidates for implantable applications due to their higher‐power conversion efficiencies and small footprint. Herein, the latest implantable energy harvesting technologies are surveyed. A comparison between the different state‐of‐the‐art power harvesting methods is also provided. Finally, recommendations are provided regarding the feasibility of PV cells as an in vivo energy harvester, with an emphasis on skin penetration, fabrication, encapsulation, durability, biocompatibility, and power management

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention