Radiosensitizing Pancreatic Cancer Xenografts by an Implantable Micro-Oxygen Generator.

Over the past decades, little progress has been made to improve the extremely low survival rates in pancreatic cancer patients. Extreme hypoxia observed in pancreatic tumors contributes to the aggressive and metastatic characteristics of this tumor and can reduce the effectiveness of conventional radiation therapy and chemotherapy. In an attempt to reduce hypoxia-induced obstacles to effective radiation treatment, we used a novel device, the implantable micro-oxygen generator (IMOG), for in situ tumor oxygenation. After subcutaneous implantation of human pancreatic xenograft tumors in athymic rats, the IMOG was wirelessly powered by ultrasonic waves, producing 30 µA of direct current (at 2.5 V), which was then utilized to electrolyze water and produce oxygen within the tumor. Significant oxygen production by the IMOG was observed and corroborated using the NeoFox oxygen sensor dynamically. To test the radiosensitization effect of the newly generated oxygen, the human pancreatic xenograft tumors were subcutaneously implanted in nude mice with either a functional or inactivated IMOG device. The tumors in the mice were then exposed to ultrasonic power for 10 min, followed by a single fraction of 5 Gy radiation, and tumor growth was monitored thereafter. The 5 Gy irradiated tumors containing the functional IMOG exhibited tumor growth inhibition equivalent to that of 7 Gy irradiated tumors that did not contain an IMOG. Our study confirmed that an activated IMOG is able to produce sufficient oxygen to radiosensitize pancreatic tumors, enhancing response to single-dose radiation therapy.

Disease-on-a-chip: mimicry of tumor growth in mammary ducts.

We present a disease-on-a-chip model in which cancer grows within phenotypically normal breast luminal epithelium on semicircular acrylic support mimicking portions of mammary ducts. The cells from tumor nodules developing within these hemichannels are morphologically distinct from their counterparts cultured on flat surfaces. Moreover, tumor nodules cocultured with the luminal epithelium in hemichannels display a different anticancer drug sensitivity compared to nodules cocultured with the luminal epithelium on a flat surface and to monocultures of tumor nodules. The mimicry of tumor development within the epithelial environment of mammary ducts provides a framework for the design and test of anticancer therapies.

A minimally invasive implantable wireless pressure sensor for continuous IOP monitoring.

This paper presents a minimally invasive implantable pressure sensing transponder for continuous wireless monitoring of intraocular pressure (IOP). The transponder is designed to make the implantation surgery simple while still measuring the true IOP through direct hydraulic contact with the intraocular space. Furthermore, when IOP monitoring is complete, the design allows physicians to easily retrieve the transponder. The device consists of three main components: 1) a hypodermic needle (30 gauge) that penetrates the sclera through pars plana and establishes direct access to the vitreous space of the eye; 2) a micromachined capacitive pressure sensor connected to the needle back-end; and 3) a flexible polyimide coil connected to the capacitor forming a parallel LC circuit whose resonant frequency is a function of IOP. Most parts of the sensor sit externally on the sclera and only the needle penetrates inside the vitreous space. In vitro tests show a sensitivity of 15 kHz/mmHg with approximately 1-mmHg resolution. One month in vivo implants in rabbits confirm biocompatibility and functionality of the device.

Atomic force microscopy-coupled microcoils for cellular-scale nuclear magnetic resonance spectroscopy.

We present the coupling of atomic force microscopy (AFM) and nuclear magnetic resonance (NMR) technologies to enable topographical, mechanical, and chemical profiling of biological samples. Here, we fabricate and perform proof-of-concept testing of radiofrequency planar microcoils on commercial AFM cantilevers. The sensitive region of the coil was estimated to cover an approximate volume of 19.4 × 103 µm3 (19.4 pl). Functionality of the spectroscopic module of the prototype device is illustrated through the detection of 1Η resonance in deionized water. The acquired spectra depict combined NMR capability with AFM that may ultimately enable biophysical and biochemical studies at the single cell level.

Biodegradable microfabricated plug-filters for glaucoma drainage devices.

We report on the development of a batch fabricated biodegradable truncated-cone-shaped plug filter to overcome the postoperative hypotony in nonvalved glaucoma drainage devices. Plug filters are composed of biodegradable polymers that disappear once wound healing and bleb formation has progressed past the stage where hypotony from overfiltration may cause complications in the human eye. The biodegradable nature of device eliminates the risks associated with permanent valves that may become blocked or influence the aqueous fluid flow rate in the long term. The plug-filter geometry simplifies its integration with commercial shunts. Aqueous humor outflow regulation is achieved by controlling the diameter of a laser-drilled through-hole. The batch compatible fabrication involves a modified SU-8 molding to achieve truncated-cone-shaped pillars, polydimethylsiloxane micromolding, and hot embossing of biodegradable polymers. The developed plug filter is 500 µm long with base and apex plane diameters of 500 and 300 µm, respectively, and incorporates a laser-drilled through-hole with 44-µm effective diameter in the center.

An ultrasonically powered implantable micro-oxygen generator (IMOG).

In this paper, we present an ultrasonically powered implantable micro-oxygen generator (IMOG) that is capable of in situ tumor oxygenation through water electrolysis. Such active mode of oxygen generation is not affected by increased interstitial pressure or abnormal blood vessels that typically limit the systemic delivery of oxygen to hypoxic regions of solid tumors. Wireless ultrasonic powering (2.15 MHz) was employed to increase the penetration depth and eliminate the directional sensitivity associated with magnetic methods. In addition, ultrasonic powering allowed for further reduction in the total size of the implant by eliminating the need for a large area inductor. IMOG has an overall dimension of 1.2 mm × 1.3 mm × 8 mm, small enough to be implanted using a hypodermic needle or a trocar. In vitro and ex vivo experiments showed that IMOG is capable of generating more than 150 µA which, in turn, can create 0.525 µL/min of oxygen through electrolytic disassociation. In vivo experiments in a well-known hypoxic pancreatic tumor models (1 cm (3) in size) also verified adequate in situ tumor oxygenation in less than 10 min.

Magnetic tracking system for radiation therapy.

Intensity-modulated radiation therapy (IMRT) requires precise delivery of the prescribed dose of radiation to the target and surrounding tissue. Irradiation of moving body anatomy is possible only if stable, accurate, and reliable information about the moving body structures are provided in real time. This paper presents a magnetic position tracking system for radiation therapy. The proposed system uses only four transmitting coils and an implantable transponder. The four transmitting coils generate a magnetic field which is sensed and measured by a biaxial magnetoresistive sensor in the transponder in the tumor. The transponder transmits the information back to a computer to determine the position of the transponder allowing it to track the tumor in real time. The transmission of the information from the transponder to the computer can be wired or wireless. Measurements using a biaxial sensor agree well with the field strength calculated from the ideal equations. The translation from the measurement data to the 3-D location and orientation requires a numerical technique because the equations are in nonclosed forms. The algorithm of tracking is implemented using MATLAB. Each calculation of the position along the target trajectory takes 30 ms, which makes the proposed system suitable for real-time tracking of the transponder for radiation assessment and delivery. An error of less than 2 mm is achieved in the demonstration.