Research

Park lab conducts three lines of research; wireless optogenetics, biomedicine, wireless power transmission into biological tissues,  and photodynamic therapy for gastrointestinal cancers.

We are developing soft neural interface platforms and soft wireless platform electronics that can control neural interfaces and integrate data transmission, signal processing, and power management. These works involve fabrication of stretchable electronic systems and development of novel antenna systems and integrated circuit systems. In parallel, we are studying novel methods to maximize wireless power transmission into biological tissues.

  • Soft Wireless Optogenetics

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A miniaturized fully implantable, stretchable optoelectronic system. The device wraps around a single grain of rice.

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An image of a mouse with the stretchable device implanted

Optogenetics allows rapid, temporally specific control of neuronal activity by targeted expression and activation of light-sensitive proteins. Implementation typically requires remote light sources and fiber-optic delivery schemes that impose considerable physical constraints on natural behaviors. We bypass these limitations using technologies that combine thin, mechanically soft neural interfaces with fully implantable, stretchable wireless radio power and control systems. The resulting devices achieve optogenetic modulation of the spinal cord and peripheral nervous system. This is demonstrated with
two form factors; stretchable film appliqués that interface directly with peripheral nerves, and flexible filaments that insert into the narrow confines of the spinal epidural space. These soft, thin devices are minimally invasive, and histological tests suggest they can be used in chronic studies. We demonstrate the power of this technology by modulating peripheral and spinal pain circuitry, providing evidence for the potential widespread use
of these devices in research and future clinical applications of optogenetics outside the brain.picture3

To determine the utility of these optoelectronic devices in studies of pain pathways, we tested whether they could modulate pain related behaviors of mice expressing ChR2 in all sensory neurons or in subpopulations of sensory neurons responsible for detection of noxious stimuli (nociceptors). Mice expressing ChR2 in all sensory neurons were generated using a cre recombinase–based transgenic approach where cre recombinase expression is driven by the promoter of the sensory neuron–specific gene Advillin (Advillin-ChR2). Electrophysiological studies show that Advillin-ChR2 sensory neurons were consistently activated by blue light, and immunohistochemical studies demonstrate that ChR2 was present in mid-axon, in the dorsal root ganglia (DRG) and in the central terminals of sensory neurons. Similar results were observed in mouse lines where ChR2 expression is restricted to nociceptor populations (TrpV1-ChR2, SNS-ChR2).

  • Soft Wireless Electronics for Biomedicinepicture4 picture15

(Top to the left) Fully implantable wireless closed loop system, (Top to the right) soft neural interface platform, and (Bottom) functional block diagram of fully implantable, stretchable wireless telemetry systems.

Capabilities in data acquisition from the neural interface systems, wireless transmission and remote, wireless control of stimulation waveforms are essential tasks in the programs proposed here.  The operational features are unavailable in commercial systems, particularly in size formats that allow complete implantation.  The work builds directly on recent work by Park on wireless devices for optogenetics.  The wireless telemetry system consists of a fully implantable receiver and a base station. The communication between the receiver and the base station will occurs via the latest in low energy Bluetooth protocols (BLE).  Here, a subcutaneously powered receiver captures neural activity recordings, initiate stimulation waveforms and control pharmacological release. For recording, the preamplifier boosts amplitudes of captured neural signals and the analog filter suppresses noise signals. Next, recorded signals are digitized, coded, modulated, and transmitted by the BLE incorporated into the receiver. Once the base station receives the signals transmitted from the receiver, it decodes the information and display raw data. In parallel, the base station can send stimulation conditions such as pulse width and duration to stimulate or inhibit neural activities. Based on the programmed condition, the BLE in the receiver decodes the signals transmitted from the base station and perform digital-to-analog conversion (pulse-width modulated signals). Next, the charge pump logic  boosts amplitudes of the pulse-width modulated signals up to 3 V required for light illumination of μLEDs. Thereby, the receiver can initiate or inhibit neural activities. In addition, the base station can produce magnetic fields at a high frequency range (13.56 Mhz) via transmission (TX) coils consisting of a source coil and a primary coil, and the magnetic fields will induce power at the receiving coils consisting of a secondary coil and a load coil.

  • Wireless power transfer into biological tissues

 

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For the devices to be useful in behavior experiments, the RF transmission(TX) systems must enable continuous operation throughout a location of interest (e.g., the home cage or testing arena), at field strengths that lie below IEEE and Federal Communications
Commission (FCC) guidelines. A configuration of four TX antennas connected to a common RF power supply provided total average RF power that was sufficient for operation (~2 W) throughout the volume of the cage, and was capable of activating multiple devices in the same region. These devices can be activated reliably up to 20 cm from the transmitters, which is ten times the reported range of any previous systems. Under these conditions, we calculated distributions of the specific absorption rate (SAR; a measure of the rate at which RF energy is absorbed by the body) and found that the SAR fell well below safety guidelines. This configuration allows consistent device activation even with rapid changes in receiver location and orientation. This is demonstrated using long-exposure images captured during motion of an operating device; continuous streaks of light illustrate activation of the devices regardless of device position or orientation.

  • Wireless platform electronics for photodynamic therapy

 

Surgery is the only curative treatment for gastrointestinal cancers, including colorectal, gastric, and pancreatic cancers. Unfortunately, surgery is frequently, complicated by local disease recurrence which manifests as cancer deposits throughout the peritoneal cavity. This is a pre-terminal event with current adjuvant therapies, including chemo- and radiotherapy, providing only limited symptomatic palliation. There is a desperate unmet clinical need to develop better strategies to prevent and treat local cancer recurrence. Local recurrence occurs when microscopic cancer cells are left behind at the time of surgery, either due to dissemination during the surgical procedure, or being present as micro-metastatic deposits within regional lymph nodes. Residual cancer cells implant in the surgical wound, which provides a cytokine and growth factor rich environment favorable to cancer cell growth. Photodynamic therapy (PDT) is an established anti-cancer therapy, which has the advantage of selectively targeting cancer cells whilst leaving normal stromal tissue unaffected. It involves the delivery of a photosensitizer that is activated by light of a specific wavelength, resulting in the generation of cytotoxic oxygen free radicals that induce apoptotic cell death. PDT is ideally suited to the treatment of local cancer recurrence within the abdominal cavity because it is a “surface disease” that requires limited light penetration. Unlike chemotherapy it is well tolerated with a good safety profile, and unlike radiotherapy it can be applied in repeated doses. PDT would have benefit in: i) the prevention of local recurrence, through prophylactic treatment of the surgical wound to mop up disseminated cancer cells, and ii) the treatment of local recurrence through direct light irradiation of the affected area. The challenge is to develop a biocompatible, implantable device that can be applied to the required area and is capable of delivering both a photosensitizer and light for PDT.