Yun Soung Kim

Dissolvable films of silk fibroin for ultrathin conformal bio-integrated electronics

Electronics that are capable of intimate, non-invasive integration with the soft, curvilinear surfaces of biological tissues offer important opportunities for diagnosing and treating disease and for improving brain/machine interfaces. This article describes a material strategy for a type of bio-interfaced system that relies on ultrathin electronics supported by bioresorbable substrates of silk fibroin. Mounting such devices on tissue and then allowing the silk to dissolve and resorb initiates a spontaneous, conformal wrapping process driven by capillary forces at the biotic/abiotic interface. Specialized mesh designs and ultrathin forms for the electronics ensure minimal stresses on the tissue and highly conformal coverage, even for complex curvilinear surfaces, as confirmed by experimental and theoretical studies. In vivo, neural mapping experiments on feline animal models illustrate one mode of use for this class of technology. These concepts provide new capabilities for implantable and surgical devices.

Flexible, foldable, actively multiplexed, high-density electrode array for mapping brain activity in vivo

Arrays of electrodes for recording and stimulating the brain are used throughout clinical medicine and basic neuroscience research, yet are unable to sample large areas of the brain while maintaining high spatial resolution because of the need to individually wire each passive sensor at the electrode-tissue interface. To overcome this constraint, we developed new devices that integrate ultrathin and flexible silicon nanomembrane transistors into the electrode array, enabling new dense arrays of thousands of amplified and multiplexed sensors that are connected using fewer wires. We used this system to record spatial properties of cat brain activity in vivo, including sleep spindles, single-trial visual evoked responses and electrographic seizures. We found that seizures may manifest as recurrent spiral waves that propagate in the neocortex. The developments reported here herald a new generation of diagnostic and therapeutic brain-machine interface devices.

A Physically Transient Form of Silicon Electronics

Reversible Implants Silicon electronics are generally designed to be stable and robust—it would be counterproductive if the key parts of your computer or cell phone slowly dissolved away while you were using it. In order to develop transient electronics for use as medical implants, Hwang et al. (p. 1640, see the cover) produced a complete set of tools and materials that would be needed to make standard devices. Devices were designed to have a specific lifetime, after which the component materials, such as porous silicon and silk, would be resorbed by the body. A platform of materials and fabrication methods furnishes resorbable electronic devices for in vivo use. A remarkable feature of modern silicon electronics is its ability to remain physically invariant, almost indefinitely for practical purposes. Although this characteristic is a hallmark of applications of integrated circuits that exist today, there might be opportunities for systems that offer the opposite behavior, such as implantable devices that function for medically useful time frames but then completely disappear via resorption by the body. We report a set of materials, manufacturing schemes, device components, and theoretical design tools for a silicon-based complementary metal oxide semiconductor (CMOS) technology that has this type of transient behavior, together with integrated sensors, actuators, power supply systems, and wireless control strategies. An implantable transient device that acts as a programmable nonantibiotic bacteriocide provides a system-level example.

Ultrathin conformal devices for precise and continuous thermal characterization of human skin

Precision thermometry of the skin can, together with other measurements, provide clinically relevant information about cardiovascular health, cognitive state, malignancy and many other important aspects of human physiology. Here, we introduce an ultrathin, compliant skin-like sensor/actuator technology that can pliably laminate onto the epidermis to provide continuous, accurate thermal characterizations that are unavailable with other methods. Examples include non-invasive spatial mapping of skin temperature with millikelvin precision, and simultaneous quantitative assessment of tissue thermal conductivity. Such devices can also be implemented in ways that reveal the time-dynamic influence of blood flow and perfusion on these properties. Experimental and theoretical studies establish the underlying principles of operation, and define engineering guidelines for device design. Evaluation of subtle variations in skin temperature associated with mental activity, physical stimulation and vasoconstriction/dilation along with accurate determination of skin hydration through measurements of thermal conductivity represent some important operational examples.

Multifunctional Epidermal Electronics Printed Directly Onto the Skin

Materials and designs are presented for electronics and sensors that can be conformally and robustly integrated onto the surface of the skin. A multifunctional device of this type can record various physiological signals relevant to health and wellness. This class of technology offers capabilities in biocompatible, non-invasive measurement that lie beyond those available with conventional, point-contact electrode interfaces to the skin.

A conformal, bio-interfaced class of silicon electronics for mapping cardiac electrophysiology.

Flexible electronics and sensors that adhere to the surfaces of living, moving tissues allow detailed mapping of cardiac electrical activity in a porcine animal model. My Beating Heart The heart is tricky to work with. Usually in constant motion, it has to be stopped for most cardiac surgery and its health is most often checked by EKG measurements of net electrical activity from outside the body. When damage to the heart causes life-threatening arrhythmias, physicians can only get a get a rough idea about where the problem is located by painstakingly recording from one part of the heart after another. Improvements in electronic circuit design and fabrication, as reported here by Viventi et al., can enable sophisticated, multiunit electrodes to stay in close contact with biological tissue, making monitoring and stimulation of the living, moving heart a realistic goal. The new type of device is a multilayer circuit fabricated on a 25-μm-thick, plastic sheet of polyimide, with a built-in array of 288 gold electrodes. It is flexible but the design keeps the sensitive electronics in the neutral plane so that it still functions, even when bent. Each electrode has its own amplifier, which magnifies the tiny biological currents, and multiplexer, which allows the output of all 288 electrodes to be conveyed by only 36 wires. Electrically active devices inside the wet interior of the body can easily leak current, so the authors guarded against this by encapsulating the device in a trilayer coating of polyimide, silicon nitride, and epoxy. Most (75%) of the devices they made leaked less than 10 μA, an industry standard, and maintained this performance for at least 3 hours. To map cardiac function with their flexible electrode array, the researchers applied it to the exposed epicardial surface of the beating porcine heart. Functional for more than 10,000 bending cycles, the electrodes could record normal heart beats or beats driven by a second pacing electrode at high resolution. With a high signal-to-noise ratio of about 34 dB, conduction of a moving wave of cardiac activation was readily apparent as it swept across the array of electrodes with each contraction. The authors constructed an isochronal map of heart activation, determining that the conduction velocity was 0.9 mm per millisecond. Heart physiology is not the only possible application for these flexible electrodes. The brain is also a curved, wet organ that can only be accessed by individually wired electrodes at present. Muscles are electrically active moving tissues, found both within internal organs and as effectors for the limbs. The ability to house electrodes, amplifiers, and multiplexers in a flexible, biocompatible plastic sheet that can snuggle up right against the organ of interest will improve our ability to stimulate and monitor living tissues. In all current implantable medical devices such as pacemakers, deep brain stimulators, and epilepsy treatment devices, each electrode is independently connected to separate control systems. The ability of these devices to sample and stimulate tissues is hindered by this configuration and by the rigid, planar nature of the electronics and the electrode-tissue interfaces. Here, we report the development of a class of mechanically flexible silicon electronics for multiplexed measurement of signals in an intimate, conformal integrated mode on the dynamic, three-dimensional surfaces of soft tissues in the human body. We demonstrate this technology in sensor systems composed of 2016 silicon nanomembrane transistors configured to record electrical activity directly from the curved, wet surface of a beating porcine heart in vivo. The devices sample with simultaneous submillimeter and submillisecond resolution through 288 amplified and multiplexed channels. We use this system to map the spread of spontaneous and paced ventricular depolarization in real time, at high resolution, on the epicardial surface in a porcine animal model. This demonstration is one example of many possible uses of this technology in minimally invasive medical devices.

Conformable amplified lead zirconate titanate sensors with enhanced piezoelectric response for cutaneous pressure monitoring

The ability to measure subtle changes in arterial pressure using devices mounted on the skin can be valuable for monitoring vital signs in emergency care, detecting the early onset of cardiovascular disease and continuously assessing health status. Conventional technologies are well suited for use in traditional clinical settings, but cannot be easily adapted for sustained use during daily activities. Here we introduce a conformal device that avoids these limitations. Ultrathin inorganic piezoelectric and semiconductor materials on elastomer substrates enable amplified, low hysteresis measurements of pressure on the skin, with high levels of sensitivity (~0.005 Pa) and fast response times (~0.1 ms). Experimental and theoretical studies reveal enhanced piezoelectric responses in lead zirconate titanate that follow from integration on soft supports as well as engineering behaviours of the associated devices. Calibrated measurements of pressure variations of blood flow in near-surface arteries demonstrate capabilities for measuring radial artery augmentation index and pulse pressure velocity.

Silicon electronics on silk as a path to bioresorbable, implantable devices

Many existing and envisioned classes of implantable biomedical devices require high performance electronicssensors. An approach that avoids some of the longer term challenges in biocompatibility involves a construction in which some parts or all of the system resorbs in the body over time. This paper describes strategies for integrating single crystalline silicon electronics, where the silicon is in the form of nanomembranes, onto water soluble and biocompatible silk substrates. Electrical, bending, water dissolution, and animal toxicity studies suggest that this approach might provide many opportunities for future biomedical devices and clinical applications.

Optimized Structural Designs for Stretchable Silicon Integrated Circuits

Materials and design strategies for stretchable silicon integrated circuits that use non-coplanar mesh layouts and elastomeric substrates are presented. Detailed experimental and theoretical studies reveal many of the key underlying aspects of these systems. The results shpw, as an example, optimized mechanics and materials for circuits that exhibit maximum principal strains less than 0.2% even for applied strains of up to approximately 90%. Simple circuits, including complementary metal-oxide-semiconductor inverters and n-type metal-oxide-semiconductor differential amplifiers, validate these designs. The results suggest practical routes to high-performance electronics with linear elastic responses to large strain deformations, suitable for diverse applications that are not readily addressed with conventional wafer-based technologies.

Thin, Flexible Sensors and Actuators as ‘Instrumented’ Surgical Sutures for Targeted Wound Monitoring and Therapy

Sutures are among the simplest and most widely used devices in clinical medicine. All existing synthetic and natural forms use thread-like geometries, as purely passive, mechanical structures that are fl exible and resilient to tensile stress. Several recent reports describe strategies to incorporate advanced functionality into this platform through the employment of shape-memory polymers that offer mechanical actuation or through the release of bioresorbable compounds that carry growth factors and antibiotics to accelerate healing. [ 1–3 ]