Milan Raj

Portable oral cancer detection using a miniature confocal imaging probe with a large field of view

We demonstrate a MEMS micromirror enabled handheld confocal imaging probe for portable oral cancer detection, where a comparatively large field of view (FOV) was generated through the programmable Lissajous scanning pattern of the MEMS micromirror. Miniaturized handheld MEMS confocal imaging probe was developed, and further compared with the desktop confocal prototype under clinical setting. For the handheld confocal imaging system, optical design simulations using CODE VR® shows the lateral and axial resolution to be 0.98 µm and 4.2 µm, where experimental values were determined to be 3 µm and 5.8 µm, respectively, with a FOV of 280 µm×300 µm. Fast Lissajous imaging speed up to 2 fps was realized with improved Labview and Java based real-time imaging software. Properties such as 3D imaging through autofocusing and mosaic imaging for extended lateral view (6 mm × 8 mm) were examined for carcinoma real-time pathology. Neoplastic lesion tissues of giant cell fibroma and peripheral ossifying fibroma, the fibroma inside the paraffin box and ex vivo gross tissues were imaged by the bench-top and handheld imaging modalities, and further compared with commercial microscope imaging results. The MEMS scanner-based handheld confocal imaging probe shows great promise as a potential clinical tool for oral cancer diagnosis and treatment.

A stretchable and flexible system for skin-mounted measurement of motion tracking and physiological signals

In this paper, we present a stretchable wearable system capable of i) measuring multiple physiological parameters and ii) transmitting data via radio frequency to a smart phone. The electrical architecture consists of ultra thin sensors (<; 20 μm thick) and a conformal network of associated active and passive electronics in a mesh-like geometry that can mechanically couple with the curvilinear surfaces of the human body. Spring-like metal interconnects between individual chips on board the device allow the system to accommodate strains approaching ~30% A representative example of a smart patch that measures movement and electromyography (EMG) signals highlights the utility of this new class of medical skin-mounted system in monitoring a broad range of neuromuscular and cardiovascular diseases.

Design for reliability of multi-layer stretchable interconnects

In this investigation, the electrical performance and reliability of multi-layer stretchable metal interconnects are evaluated using numerical simulations and experimental analysis. The numerical results show that the bi-layer design of stretchable interconnects have similar mechanics when compared to single layer interconnect structures. In contrast, interconnects configured in an in-plane stacked arrangement exhibit increased equivalent plastic strain during elongation, and consequently support less stretching. Our experimental results support these numerical findings. Maximum stretchability approaches ~150% elongation for single layer and bi-layer interconnects. In addition, fatigue experiments at 60% elongation show that the bi-layer design of stretchable interconnects have life cycles three orders of magnitude higher than the in-plane stacked arrangement of stretchable interconnects.

Intraoperative monitoring of neuromuscular function with soft, skin-mounted wireless devices

Peripheral nerves are often vulnerable to damage during surgeries, with risks of significant pain, loss of motor function, and reduced quality of life for the patient. Intraoperative methods for monitoring nerve activity are effective, but conventional systems rely on bench-top data acquisition tools with hard–wired connections to electrode leads that must be placed percutaneously inside target muscle tissue. These approaches are time and skill intensive and therefore costly to an extent that precludes their use in many important scenarios. Here we report a soft, skin-mounted monitoring system that measures, stores, and wirelessly transmits electrical signals and physical movement associated with muscle activity, continuously and in real-time during neurosurgical procedures on the peripheral, spinal, and cranial nerves. Surface electromyography and motion measurements can be performed non-invasively in this manner on nearly any muscle location, thereby offering many important advantages in usability and cost, with signal fidelity that matches that of the current clinical standard of care for decision making. These results could significantly improve accessibility of intraoperative monitoring across a broad range of neurosurgical procedures, with associated enhancements in patient outcomes.Wireless biosensors: easing intraoperative monitoringA small skin-mounted biosensing device accurately and non-invasively monitors neuromuscular activity in real-time during surgery. With many surgical procedures there is a risk of nerve damage. Although this is often temporary, in some cases it can significantly affect patients’ quality of life. Existing monitoring systems that rely on the accurate placement of needle electrodes into target nerves are cumbersome and expensive. The device developed by a team led by John Rogers, at Northwestern University, and Michel Kliot, at Stanford University, can easily be accommodated to any part of the body to monitor muscle activity in response to nerve impulses and stimulation during surgery. Furthermore, it can wirelessly transmit signals of comparable quality to needle-based systems. These devices could not only increase the use of intraoperative monitoring in hospitals but also contribute to make surgery safer.

A wearable computing platform for developing cloud-based machine learning models for health monitoring applications

Wearable sensors have the potential to enable clinical-grade ambulatory health monitoring outside the clinic. Technological advances have enabled development of devices that can measure vital signs with great precision and significant progress has been made towards extracting clinically meaningful information from these devices in research studies. However, translating measurement accuracies achieved in the controlled settings such as the lab and clinic to unconstrained environments such as the home remains a challenge. In this paper, we present a novel wearable computing platform for unobtrusive collection of labeled datasets and a new paradigm for continuous development, deployment and evaluation of machine learning models to ensure robust model performance as we transition from the lab to home. Using this system, we train activity classification models across two studies and track changes in model performance as we go from constrained to unconstrained settings.

Archipelago platform for skin-mounted wearable and stretchable electronics

In this investigation, the “archipelago” design is presented as a platform for skin-mounted wearable and stretchable electronics. The electronic components of the design were distributed between islands connected by stretchable serpentine structures. The analytical results show that at 20% overall elongation, the serpentines stretch 60% due to the rigidity of the islands. This 20% elongation is defined as the system stretchability. The 60% elongation on the serpentines is defined as the effective stretchability. At 60% effective stretch, the calculated equivalent plastic strain in a serpentine interconnect is 0.67%, which is well below the fracture limit of copper. Elongation experiments show that the archipelago structure has the system stretchability up to 76% for one-time-stretching, translating to 228% of the effective stretchability on the serpentines. Fatigue-tension experiments show that at 20% system stretch, the archipelago structure can withstand on average 71,950 cycles without electrical or mechanical degradation.

Portable oral cancer detection using miniature confocal imaging probe with large field of view

We demonstrate MEMS micromirror enabled hand-held confocal imaging probe for portable oral cancer detection, where large field of view (FOV) is achieved through the lissajous scanning operation of the MEMS mirror. The imaging speed up to 2 frames per second was demonstrated with the improved Labview and Java based data acquisition and control programs. We also examined the axial resolution (3.4 um) and large FOV (1mm × 1mm) through mosaic imaging using the handheld imaging probe. Multiple clinical samples, including neoplastic lesion tissues of giant cell fibroma, epithelial ossifying fibroma, the fibroma inside the paraffin box and ex-vivo gross tissue, were scanned using the compact imaging modalities. The quality of the images acquired is comparable to those from commercial microscopes.

Soft, Skin-Interfaced Microfluidic Systems with Wireless, Battery-Free Electronics for Digital, Real-Time Tracking of Sweat Loss and Electrolyte Composition

Sweat excretion is a dynamic physiological process that varies with body position, activity level, environmental factors, and health status. Conventional means for measuring the properties of sweat yield accurate results but their requirements for sampling and analytics do not allow for use in the field. Emerging wearable devices offer significant advantages over existing approaches, but each has significant drawbacks associated with bulk and weight, inability to quantify volumetric sweat rate and loss, robustness, and/or inadequate accuracy in biochemical analysis. This paper presents a thin, miniaturized, skin-interfaced microfluidic technology that includes a reusable, battery-free electronics module for measuring sweat conductivity and rate in real-time using wireless power from and data communication to electronic devices with capabilities in near field communications (NFC), including most smartphones. The platform exploits ultrathin electrodes integrated within a collection of microchannels as interfaces to circuits that leverage NFC protocols. The resulting capabilities are complementary to those of previously reported colorimetric strategies. Systematic studies of these combined microfluidic/electronic systems, accurate correlations of measurements performed with them to those of laboratory standard instrumentation, and field tests on human subjects exercising and at rest establish the key operational features and their utility in sweat analytics.

Relation between blood pressure and pulse wave velocity for human arteries

Significance Continuous, cuffless, and noninvasive blood pressure monitoring by measuring the pulse wave velocity is generally considered to be a promising technique for noninvasive measurements. Previously reported relations between blood pressure and pulse wave velocity relation involve unrealistic assumptions that do not hold for human arteries, and also rely on empirical expressions without any theoretical basis. Here, an analytical model without such assumptions or empirical expressions is established to yield a relation between blood pressure and pulse wave velocity that has general utility for future work in continuous, cuffless, and noninvasive blood pressure monitoring. Continuous monitoring of blood pressure, an essential measure of health status, typically requires complex, costly, and invasive techniques that can expose patients to risks of complications. Continuous, cuffless, and noninvasive blood pressure monitoring methods that correlate measured pulse wave velocity (PWV) to the blood pressure via the Moens−Korteweg (MK) and Hughes Equations, offer promising alternatives. The MK Equation, however, involves two assumptions that do not hold for human arteries, and the Hughes Equation is empirical, without any theoretical basis. The results presented here establish a relation between the blood pressure P and PWV that does not rely on the Hughes Equation nor on the assumptions used in the MK Equation. This relation degenerates to the MK Equation under extremely low blood pressures, and it accurately captures the results of in vitro experiments using artificial blood vessels at comparatively high pressures. For human arteries, which are well characterized by the Fung hyperelastic model, a simple formula between P and PWV is established within the range of human blood pressures. This formula is validated by literature data as well as by experiments on human subjects, with applicability in the determination of blood pressure from PWV in continuous, cuffless, and noninvasive blood pressure monitoring systems.

Multifunctional Epidermal Sensor Systems with Ultrathin Encapsulation Packaging for Health Monitoring

Wearable sensors have the potential to enable longitudinal, objective health monitoring in patients with chronic diseases, including cardiac rhythm disorders, neurological and movement disorders, diabetes, and pain. However, conventional wearable devices are typically comprised of rigid, packaged electronics, which may compromise overall signal fidelity and wearer comfort during activities of daily living and sleep. In this chapter, we present recent advances in the development of thin and stretchable epidermal systems for biometric data measurements. These non-invasive epidermal systems are fully integrated with multiple sensors, an analog front end module, a radio for wireless communication , onboard flash memory, a rechargeable battery all encapsulated in a soft, stretchable and water-resistant silicone, and with an air permeable adhesive layer that interfaces with the human skin. The encapsulated system intimately couples with the skin at multiple locations on the body. We present results showing the potential of this technology to quantitatively assess bio-kinematics and electrophysiological signals. Finally, we provide perspectives on remaining challenges and opportunities to achieve clinical validation and commercial adoption of these technologies.