CMOS MULTI-MODAL INTEGRATED SYSTEMS FOR FUTURE BIOELECTRONICS AND BIOSENSORS

Cells are the basic structural biological units of all known living organisms. They are highly sophisticated system with thousands of molecules operating in hundreds of pathways to maintain their proper functions, phenotypes, and physiological behaviors. With this scale of complexity, cells often exhibit multi-physiological properties as their cellular fingerprints from external stimulations. In order to further advance the frontiers in bioscience and biotechnologies such as stem cell manufacturing, synthetic biology, and regenerative medicine, it is required to comprehend complex cell physiology of living cells. Therefore, a comprehensive set of technologies is needed to harvest quantitative biological data from given cell samples. Such demands have stimulated extensive research on new bioelectronics and biosensors to characterize their functional information by converting their biological activities to electrical signals. As a result, various bioelectronics and biosensors are reported and employed in many in vivo and in vitro applications. Since sensing electrodes of the devices are physically in touch with biological/chemical samples and record their signals, long-term biocompatibility and chemical/mechanical stability is of paramount importance in numerous biological applications. Furthermore, the devices should achieve high sensitivity/resolution/linearity, large field-of-view (FoV), multi-modal sensing, and real-time monitoring, while maintaining small feature size of devices to use small volume of biological/chemical samples and reduce cost. As a result, My Ph.D research aims to study interfacial electrochemical impedance spectroscopy (EIS) of electrodes with different combination of materials/sizes and to design novel multi-modal sensing/actuation array architectures with CMOS compatible in-house post-processing to address the design challenges of the bioelectronics and biosensors.Ph.D

Wearable Devices for Single-Cell Sensing and Transfection

Wearable healthcare devices are mainly used for biosensing and transdermal delivery. Recent advances in wearable biosensors allow for long-term and real-time monitoring of physiological conditions at a cellular resolution. Transdermal drug delivery systems have been further scaled down, enabling wide selections of cargo, from natural molecules (e.g., insulin and glucose) to bioengineered molecules (e.g., nanoparticles). Some emerging nanopatches show promise for precise single-cell gene transfection in vivo and have advantages over conventional tools in terms of delivery efficiency, safety, and controllability of delivered dose. In this review, we discuss recent technical advances in wearable micro/nano devices with unique capabilities or potential for single-cell biosensing and transfection in the skin or other organs, and suggest future directions for these fields. Highlights • Current wearable sensors have allowed for long-term, real-time detection of specific biomarkers directly from patients. • Miniaturized wearable biosensors with sensing elements interacting with skin or organs can capture target molecules from single cells, which results in significantly increased sensitivity, responding time, and precision. • Emerging wearable devices based on novel nanomaterials or nanofabrication show potential for single-cell detection in cancer cell screening, cardiomyocyte detection, and optogenetics. • Transdermal delivery devices have been scaled down to the micro- and/or nanoscale, and their applications have extended to wide selections of natural molecules and bioengineered molecules. • Emerging nanodevices show unique capabilities in precise single-cell gene transfection in vivo, with improved delivery efficiency, safety, and dose controllability

A Multimodal Neural Activity Readout Integrated Circuit for Recording Fluorescence and Electrical Signals

Monitoring the electrical neural signals is an important method for understanding the neuronal mechanism. In particular, in order to perform a cell-type-specific study, it is necessary to observe the concentration of calcium ions using fluorescent indicators in addition to measuring the electrical neural signal. This paper presents a multimodal multichannel neural activity readout integrated circuit that can perform not only electrical neural recording but also fluorescence recording of neural activity for the cell-type-specific study of heterogeneous neuronal cell populations. For monitoring the calcium ions, the photodiode generates the current according to the fluorescence expressed by the reaction between the genetically encoded calcium indicators and calcium ions. The time-based fluorescence recording circuit then records the photodiode current. The electrical neural signal captured by the microelectrode is recorded through the low-noise amplifier, variable gain amplifier, and analog-to-digital converter. The proposed integrated circuit is fabricated in a 1-poly 6-metal (1P6M) 0.18- ??m CMOS process. The fluorescence recording circuit achieves a recording range of 81 dB (75 pA to 860 nA) and consumes a power of 724 nW/channel. The electrical recording circuit achieves an input-referred noise of 2.7 ??Vrms over the bandwidth of 10 kHz, while consuming the power of 4.9 ??W /channel. The functionality of the proposed circuits is verified through the in vivo and in vitro experiments. Compared to the conventional neuroscience tools, which consist of bulky off-chip components, this neural interface is implemented in a compact size to perform multimodal neural recording while consuming low power

Design and implementation of a multi-modal sensor with on-chip security

With the advancement of technology, wearable devices for fitness tracking, patient monitoring, diagnosis, and disease prevention are finding ways to be woven into modern world reality. CMOS sensors are known to be compact, with low power consumption, making them an inseparable part of wireless medical applications and Internet of Things (IoT). Digital/semi-digital output, by the translation of transmitting data into the frequency domain, takes advantages of both the analog and digital world. However, one of the most critical measures of communication, security, is ignored and not considered for fabrication of an integrated chip. With the advancement of Moore\u27s law and the possibility of having a higher number of transistors and more complex circuits, the feasibility of having on-chip security measures is drawing more attention. One of the fundamental means of secure communication is real-time encryption. Encryption/ciphering occurs when we encode a signal or data, and prevents unauthorized parties from reading or understanding this information. Encryption is the process of transmitting sensitive data securely and with privacy. This measure of security is essential since in biomedical devices, the attacker/hacker can endanger users of IoT or wearable sensors (e.g. attacks at implanted biosensors can cause fatal harm to the user). This work develops 1) A low power and compact multi-modal sensor that can measure temperature and impedance with a quasi-digital output and 2) a low power on-chip signal cipher for real-time data transfer

Terahertz (THz) biophotonics technology : instrumentation, techniques, and biomedical applications

Terahertz (THz) technology has experienced rapid development in the past two decades. Growing numbers of interdisciplinary applications are emerging, including material science, physics, communications, security, as well as biomedicine. THz biophotonics involves studies applying THz photonic technology in biomedicine, which has attracted attention due to the unique features of THz waves, such as the high sensitivity to water, resonance with biomolecules, favourable spatial resolution, capacity to probe the water-biomolecule interactions and non-ionizing photon energy. Despite the great potential, THz biophotonics is still at an early stage of development. There is a lack of standards for instrumentation, measurement protocols, and data analysis which makes it difficult to make comparisons among all the work published. In this article we give a comprehensive review of the key findings which have underpinned research into biomedical applications of THz technology. In particular, we will focus on the advances made in general THz instrumentation and specific THz-based instruments for biomedical applications. We will also discuss the theories describing the interaction between THz light and biomedical samples. We aim to provide an overview of both, basic biomedical research, as well as pre-clinical and clinical applications under investigation. The paper aims to provide a clear picture of the achievements, challenges and future perspectives of THz biophotonics

Laboratory technology research - abstracts of FY 1997 projects

The Laboratory Technology Research (LTR) program supports high-risk, multidisciplinary research partnerships to investigate challenging scientific problems whose solutions have promising commercial potential. These partnerships capitalize on two great strengths of this country: the world-class basic research capability of the DOE Energy Research (ER) multi-program national laboratories and the unparalleled entrepreneurial spirit of American industry. A distinguishing feature of the ER multi-program national laboratories is their ability to integrate broad areas of science and engineering in support of national research and development goals. The LTR program leverages this strength for the Nation`s benefit by fostering partnerships with US industry. The partners jointly bring technology research to a point where industry or the Department`s technology development programs can pursue final development and commercialization. Projects supported by the LTR program are conducted by the five ER multi-program laboratories. These projects explore the applications of basic research advances relevant to DOE`s mission over a full range of scientific disciplines. The program presently emphasizes three critical areas of mission-related research: advanced materials; intelligent processing/manufacturing research; and sustainable environments

ADHERENS JUNCTION ENGAGEMENT REGULATES FUNCTIONAL PATTERNING OF THE CARDIAC PACEMAKER CELL LINEAGE

The heart is the first organ system to form in the embryo. Over the course of development, cardiomyocytes with differing morphogenetic, molecular, and physiological characteristics are specified and differentiate and integrate with one another to assemble a coordinated electromechanical pumping system that can function independently of any external stimulus. As congenital malformation of the heart presents the leading class of birth defects seen in humans, the molecular genetics of heart development have garnered much attention over the last half century. However, understanding how genetic perturbations manifest at the level of the individual cell function remains challenging to investigate. In this dissertation, we briefly introduce the history of imaging approaches for assessing cardiac development, describe some of the reagents and tools required to perform live imaging in the developing heart, and discuss how the combination of modern imaging modalities and physiological probes can be used to scale from subcellular to whole-organ analysis. Through these types of imaging approaches, critical insights into the processes of cardiac physiological development can be directly examined in real-time. Moving forward, the synthesis of modern molecular biology and imaging approaches will open novel avenues to investigate the mechanisms of cardiomyocyte maturation. Specifically, cardiac pacemaker cells (CPCs) will be discussed in detail. CPCs rhythmically initiate the electrical impulses that drive heart contraction. CPCs display the highest rate of spontaneous depolarization in the heart despite being subjected to inhibitory electrochemical conditions that should theoretically suppress their activity. While several models have been proposed to explain this apparent paradox, the actual molecular mechanisms that allow CPCs to overcome electrogenic barriers to their function remain poorly understood. Here, we have traced CPC development at single-cell resolution and uncovered a series of cytoarchitectural patterning events that are critical for proper pacemaking. Specifically, our data reveal that CPCs dynamically modulate adherens junction (AJ) engagement to control characteristics including surface area, volume, and gap junctional coupling. This allows CPCs to adopt a structural configuration that supports their overall excitability. Thus, our data have identified a direct role for local cellular mechanics in patterning critical morphological features that are necessary for CPC electrical activity.Doctor of Philosoph

Aerial Vehicles

This book contains 35 chapters written by experts in developing techniques for making aerial vehicles more intelligent, more reliable, more flexible in use, and safer in operation.It will also serve as an inspiration for further improvement of the design and application of aeral vehicles. The advanced techniques and research described here may also be applicable to other high-tech areas such as robotics, avionics, vetronics, and space

NASA technology applications team: Applications of aerospace technology

Two critical aspects of the Applications Engineering Program were especially successful: commercializing products of Application Projects; and leveraging NASA funds for projects by developing cofunding from industry and other agencies. Results are presented in the following areas: the excimer laser was commercialized for clearing plaque in the arteries of patients with coronary artery disease; the ultrasound burn depth analysis technology is to be licensed and commercialized; a phased commercialization plan was submitted to NASA for the intracranial pressure monitor; the Flexible Agricultural Robotics Manipulator System (FARMS) is making progress in the development of sensors and a customized end effector for a roboticized greenhouse operation; a dual robot are controller was improved; a multisensor urodynamic pressure catherer was successful in clinical tests; commercial applications were examined for diamond like carbon coatings; further work was done on the multichannel flow cytometer; progress on the liquid airpack for fire fighters; a wind energy conversion device was tested in a low speed wind tunnel; and the Space Shuttle Thermal Protection System was reviewed