Integrated Microsystems for Wireless Sensing Applications

Personal health monitoring is being considered the future of a sustainable health care system. Biosensing platforms are a very important component of this system. Real-time and accurate sensing is essential for the success of personal health care model. Currently, there are many efforts going on to make these sensors practical and more useful for such measurements. Implantable sensors are considered the most widely applicable and most reliable sensors for such accurate health monitoring applications. However, macroscopic (cm scale) size has proved to be a limiting factor for successful use of these systems for long time and in large numbers. This work is focused to resolve the issues related with miniaturizing these devices to a microscopic (mm scale) size scale which can minimize many practical difficulties associated with their larger counterparts currently. To accomplish this goal of miniaturization while retaining or even improving on the necessary capabilities for such sensing platforms, an integrated approach is presented which focuses on system-level miniaturization using standard fabrication procedures. First, it is shown that a completely integrated and wireless system is the best solution to achieve desired miniaturization without sacrificing the functionality of the system. Hence, design and implementation of the different components comprising the complete system needs to be done according to the requirements of the overall integrated system. This leads to the need of on-chip functional sensors, integrated wireless power supply, integrated wireless communication and integrated control system for realization of such system. In this work, different options for implementation of each of these subsystems are compared and an optimal solution is presented for each subsystem. For such complex systems, it is imperative to use a standard fabrication process which can provide the required functionality for all subsystems at smallest possible size scale. Complementary Metal Oxide Semiconductor (CMOS) process is the most appropriate of the technologies in this regard and has enabled incredible miniaturization of the computing industry. It also provides options for designing different subsystems on the same platform in a monolithic process with very high yield. This choice then leads to actual designs of subsystems in the CMOS technology using different possible methods. Careful comparison of these subsystems provides insights into different design adjustments that are made until the desired functions are achieved at the desired size scale. Integration of all these compatible subsystems in the same platform is shown to provide the smallest possible sensing platform to date. The completely wireless system can measure a host of different important analyte and can transmit the data to an external device which can use it for appropriate purpose. Results on measurements in phosphate buffer solution, blood serum and whole blood along with wireless communication in real biological tissues are provided. Specific examples of glucose and DNA sensors are presented and the use for many other relevant applications is also proposed. Finally, insights into animal model studies and future directions of the research are discussed. </p

Development of non-invasive, optical methods for central cardiovascular and blood chemistry monitoring.

Cardiovascular disease and sepsis are leading causes of mortality, morbidity and high cost in hospitals around the world. Failure of the circulatory system during cardiogenic shock and sepsis both can significantly impair the perfusion of oxygen through organs, resulting in poor patient outcome if not detected and corrected early. Another common disorder which goes hand-in-hand with cardiovascular disease is Diabetes Mellitus. Diabetes is a metabolic disorder resulting from the inability of the body to regulate the level of glucose in the blood. The prevalence of diabetes worldwide is increasing faster than society’s ability to manage cost effectively, with an estimated 9% of the world population diagnosed with metabolic disease. The current gold standard measurements for venous oxygen saturation, arterial pulse wave velocity (PWV), and diabetes management through blood glucose concentration monitoring are all invasive. Invasive measurements increase risk of infection and com- plications, are often high cost and disposable, and have a low patient compliance to regular measurements. The aim of this thesis is to develop non-invasive methods of monitoring these important dynamic physiological variables, including, venous oxygen saturation, pulse wave velocity, and blood glucose concentration. A novel photoplethysmography-based NIR discrete wavelength spectrometer was developed using LEDs to both emit light, and detect the light reflected back through the tissue. Using LEDs to detect light simplifies sensing circuit design, lowering hardware costs, allowing adaptable sensing specific to the needs of the user. A reflectance pulse oximeter was developed to measure the oxygen saturation at both the external jugular vein, and carotid artery. Measuring the jugular venous pulse (JVP) allows estimation of the venous oxygen saturation through either the JVP, or through breathing induced variation of the JVP. In addition to oxygenation, the de- vice developed is capable of adapting the sensing layout to measure the arterial pulse waveform at multiple sites along a peripheral artery, such as the carotid or radial. The PWV local to the carotid artery, and radial artery can then be measured, providing key information of cardiovascular risk. A novel algorithm for PWV measurement over multiple pulse waveforms was also developed. Expanding the sensor to use multiple different wavelength LEDs allow discrete spectroscopy in pulsatile blood. An absorption model of components in blood at specific wavelengths was created to isolate the spectral fingerprint of glucose. The sensor successfully measured the oxygen saturation at the carotid artery, and external jugular vein across 15 subjects, giving mean oxygen saturations of 92% and 85% respectively, within the expected physiological ranges. Venous oxygen saturation calculated using breathing induced changes to JVP was 3.3% less than when calculated on the JVP alone, with a standard deviation of 5.3%, compared to 6.9%. Thus, future work on the sensor will focus on extraction of the breathing induced venous pulse, rather than measuring from the JVP itself. The PWV on the carotid and radial artery was successfully measured within the ex- pected physiological ranges, with the novel phase difference algorithm proving more robust to noise than the gold standard foot-foot method. The phase difference method returned a mean PWV at the radial artery of 4.7 ±0.6 m s−1, and a mean CoV of 20%, compared to 4.0 ±1.4 m s−1, and a moan CoV of 58% for the foot-foot method. The proof of concept PWV sensor gives promising results, but needs to be calibrated against invasive gold standards, such as aorta and femoral pressure catheters. A glucose trial involving adult and neonatal subjects provided validation of the NIR non-invasive pulse glucometer. The sensor has an R2 of 0.47, and a mean absolute relative difference (MARD) of 19% compared to gold standard reference measurements. Clarke error grid analysis returns 85% of measurements in Zone A, 11% in Zone B, and 4% in Zone C. While the sensor is not as accurate as the gold standard invasive measurements, the ability to constantly measure without any pain or discomfort will help increase measurement compliance, improving user quality of life, plus further development may improve this. Overall, this thesis provided novel contributions in non-invasive venous oxygen saturation, PWV, and glucose concentration monitoring. The adaptability of the sensor shows promise in helping reduce the pain and inconvenience of the current invasive measurements, especially in diabetes management, where the sensor has the most potential for impact

Wearable chemo/bio-sensors for sweat sensing in sports applications: combining micro-fluidics and novel materials

In the last decade, we have witnessed an exponential growth in the area of clinical diagnostic but surprisingly little has been done on the development of wearable chemo/bio-sensors in the field of sports science. In particular, the use of wearable wireless sensors capable of analysing sweat during physical exercise can provide access to new information sources that can be used to optimise and manage athletes’ performance. Lab-on-a-Chip technology provides a fascinating opportunity for the development of such wearable sensors. In this thesis two different colorimetric wearable microfluidic devices for real- time pH sensing were developed and used during athlete training activity. In one case a textile-based microfluidic platform employing cotton capillarity to drive sweat toward the pH sensitive area is presented that avoids the use of bulky fluid handling apparatus, i.e. pumps. The second case presents a wearable micro-fluidic device based on the use of pH responsive ionogels to obtain real-time sweat pH measurements through photo analysis of their colour variation. The thesis also presents the first example of sweat lactate sensing using an organic electrochemical transistor incorporating an ionogel as solid-state electrolyte. In this chapter, optimization of the lactate oxidase stability when dissolved in number of hydrated ionic liquids is investigated. Finally, a new fabrication protocol for paper-based microfluidic technology is presented, which may have important implications for future applications such as low-cost diagnostics and chemical sensing technologies

Selected Papers from the 1st International Electronic Conference on Biosensors (IECB 2020)

The scope of this Special Issue is to collect some of the contributions to the First International Electronic Conference on Biosensors, which was held to bring together well-known experts currently working in biosensor technologies from around the globe, and to provide an online forum for presenting and discussing new results. The world of biosensors is definitively a versatile and universally applicable one, as demonstrated by the wide range of topics which were addressed at the Conference, such as: bioengineered and biomimetic receptors; microfluidics for biosensing; biosensors for emergency situations; nanotechnologies and nanomaterials for biosensors; intra- and extracellular biosensing; and advanced applications in clinical, environmental, food safety, and cultural heritage fields

Characterisation of Skin-based THz Communication Channel for Nano-scale Body-centric Wireless Networks

PhDIn pursuit of enhancing the capabilities of healthcare diagnostics and monitoring, the electromagnetic spectrum has been utilized efficiently from the MHz up to THz and beyond. The era of smart phones, wearable devices and on-body networks have unfolded plethora of health applications with efficient channel communication mechanisms, faster data transfer rates and multi-user functionalities. With the advancement in material fabrication and spectroscopic techniques, a new realm of healthcare nanodevices have emerged with immense potential to garner in-depth information of the human body, real-time of tissue morphology, molecular features, hydration level and atmospheric water vapour on channel parameters. In addition to this, engineered skin substitute models: 2D collagen and 3D organotypics, are investigated to address the importance of individual biological features comprising of water dynamics and cell culture, affecting the channel parameters. The experimental results of various tissue samples, skin substitutes and numerical evalua-tion of channel parameters can be used to further improve the communication capabilities of in-body nanonetworks. The original contributions on characterization of skin substitutes can be applied to study various health conditions, effects of drugs and skin ageing on a molecular level. The results presented in this thesis, foresee an increasing demand in skin substitute models due to their biological flexibility and control according to desired medical applications. monitoring and tackle medical emergencies. A collection of these devices with sensing capabilities together form a nanonetwork performing computing tasks such as storage, actuation, data transfer and communication. The thesis brings forth the analysis and optimization of channel parameters; such as pathloss and molecular noise temperature, when the proposed in-body nanodevices communicate amongst each other in the terahertz (THz) range. The novel contribution of the work is mapping the optical properties of human skin by bringing together the measurement of various skin tissues and its influence on channel parameters. In the later part of the thesis, emphasis is given on the individual biological entities of the tissue contributing to channel parameters, such as collagen as an abundant protein, variation in fibrous extra-cellular matrix due to fibroblast cells and amalgamation of different layers; namely, epidermis and dermis of the skin. Recently proposed graphene-based antennas resolve the cumbersomeness of existing medical devices by drastically reducing its size to a few hundreds of nanometres. These biocompatible nanodevices focus on exchanging the intricate details of the human body via nanoscale electromagnetic communication in the terahertz domain of the spectrum. The thesis aims to investigate the material properties of skin tissues with terahertz time do-main spectroscopy and numerically evaluate the channel parameters for in-body nanoscale networks that potentially would form an essential part of a hierarchical body-centric communication network extending from inside the human body to a wider community network. The results are presented in regards to the complexity of human tissue as a channel medium. The measured refractive index and absorption coefficient data is applied to numerically calculate channel pathloss and molecular noise temperature. The results provide a real-time analysi

Remote sensing of strong emotions using electro-optical imaging technique

©Cranfield UniversityThis thesis reports a summary of the PhD programme for the assessment of person‘s emotional anxiety using Electro-optical technology. The thesis focuses mainly on the understanding of fundamental properties of physiological responses to emotional anxiety and how they can be captured by using Electro-optical (EO) imaging methods such as hyperspectral imaging (HSI) and thermal imaging (TI) techniques. The thesis summarises three main areas of work that have been undertaken by the author in the programme: (a) Experimental set up including HSI system and data acquisition software design and implementation, (b) fundamental understanding of physiological responses to emotional anxiety from the EO perspective and (c) the development of a novel remote sensing technique for the assessment of emotions without the requirement of base line information. One of our main results is to provide evidence to prove that the mean temperature in the periorbital region remains the same within 0.2°C during emotional anxiety. Furthermore, we have shown that it is the high temperature pixels within the periorbital, which increases in numbers by a huge amount after 2 minutes of the onset of anxiety. We have also developed techniques to allow the assessment anxiety without the need of base line information. The method has been tested using a sample size of about 40 subjects, and achieved promising result. Technologies for the remote sensing of heart beat rate has been in great demand, this study also involves the development of heart beat detection using TI system. Moreover, we have also attempted for the first time to sense glucose concentration from the blood sample in-vivo using HSI technique remotely

Photovoltaic Energy Harvesting for Millimeter-Scale Systems

The Internet of Things (IoT) based on mm-scale sensors is a transformational technology that opens up new capabilities for biomedical devices, surveillance, micro-robots and industrial monitoring. Energy harvesting approaches to power IoT have traditionally included thermal, vibration and radio frequency. However, the achievement of efficient energy scavenging for IoT at the mm-scale or sub mm-scale has been elusive. In this work, I show that photovoltaic (PV) cells at the mm-scale can be an alternative means of wireless power transfer to mm-scale sensors for IoT, utilizing ambient indoor lighting or intentional irradiation of near-infrared (NIR) LED sources through biological tissue. Single silicon and GaAs photovoltaic cells at the mm-scale can achieve a power conversion efficiency of more than 17 % for silicon and 30 % for GaAs under low-flux NIR irradiation at 850 nm through the optimized device structure and sidewall/surface passivation studies, which guarantees perpetual operation of mm-scale sensors. Furthermore, monolithic single-junction GaAs photovoltaic modules offer a means for series-interconnected cells to provide sufficient voltage (> 5 V) for direct battery charging, and bypassing needs for voltage up-conversion circuitry. However, there is a continuing challenge to miniaturize such PV systems down to the sub mm-scale with minimal optical losses from device isolation and metal interconnects and efficient voltage up-conversion. Vertically stacked dual-junction PV cells and modules are demonstrated to increase the output voltage per cell and minimize area losses for direct powering of miniature devices for IoT and bio-implantable applications with low-irradiance narrowband spectral illumination. Dual-junction PV cells at small dimensions (150 µm x 150 µm) demonstrate power conversion efficiency greater than 22 % with more than 1.2 V output voltage under low-flux 850 nm NIR LED illumination, which is sufficient for batteryless operation of miniaturized CMOS IC chips. The output voltage of dual-junction PV modules with eight series-connected single cells is greater than 10 V while maintaining an efficiency of more than 18 %. Finally, I demonstrate monolithic PV/LED modules at the µm-scale for brain-machine interfaces, enabling two-way optical power and data transfer in a through-tissue configuration. The wafer-level assembly plan for the 3D vertical integration of three different systems including GaAs LED/PV modules, CMOS silicon chips, and neural probes is proposed.PHDElectrical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/163261/1/esmoon_1.pd

삽입형 의료 장치 및 광전자 소자를 위한 차세대 유연 물질의 설계와 제작

학위논문 (박사)-- 서울대학교 대학원 : 화학생물공학부 에너지환경화학융합기술전공, 2017. 2. 김대형.Soft electronics provide new opportunities on biomedical devices and optoelectronic devices since they offer flexible and conformable mechanical properties. Compared to commercialized rigid electronics, the soft electronics enables more accurate sensing from the curvilinear biological interface and tunable light incidence for optoelectronics. In this thesis, fabrication and application of soft medical devices and unconventional optoelectronic devices are developed based on the design and synthesis of bioresorbable and perovskite materials. Firstly, soft bioresorbable medical devices are designed and fabricated, which provide novel therapeutic guideline to overcome many challenges remaining for the treatment of glioblastoma. The integrated bioresorbable devices are composed of wireless heater, wireless temperature sensor and synthesized bioresorbable drug reservoir conformally adhered to the brain tissue provides localized, highly penetrative and controllable intracranial drug delivery. Based on the fabrication technique of bioresorbable materials, transient memory system is proposed and developed, which shows fast and complete chemical destruction of stored data by wide-range optical stimulation. The system can be established by the integration of transient ultrathin resistive random access memory (RRAM) with multi-dye-sensitized upconverting nanoparticles (UCNPs) and provides new opportunities in mobile and defense application. The final goal of this study is high-definition patterning of inorganic-organic hybrid perovskite thin films which have attracted great attention since it is regarded as an alternative to silicon in the optoelectronic devices. A new method so called Spin-on-patterning (SoP) enables the patterning of perovskite thin film which has hardly been accomplished due to their extreme instability in solvents like bioresorbable materials. The patterned perovskite photodiode is fabricated and has potential for future ultrathin image sensor array.Chapter 1. Introduction 1 1.1 Soft electronics 1 1.2 Soft bioresorbable electronics 7 1.3 Soft perovskite electronics 15 1.4 References 16 Chapter 2. Design, synthesis and fabrication of bioresorbable electronic patch for glioblastoma 24 2.1 Introduction 25 2.2 Result and Discussion 27 2.3 Conclusion 48 2.4 Experimental 49 2.5 References 58 Chapter 3. Integration of destructible resistive memory and multi-dye-sensitized upconverting nanoparticles for information security application 64 3.1 Introduction 64 3.2 Result and Discussion 67 3.3 Conclusion 99 3.4 Experimental 100 3.5 References 112 Chapter 4. High-resolution spin-on-patterning of perovskite thin films for optoelectronic device array 121 3.1 Introduction 121 3.2 Result and Discussion 124 3.3 Conclusion 144 3.4 Experimental 145 3.5 References 150 Bibliography 155 국문 초록 (Abstract in Korean) 157Docto