Implantable wireless micro-devices for enhancing radiation treatment efficacy

Radiation therapy administered with surgery and/or chemotherapy is a powerful method to treat cancer. Effective radiation therapy requires a multidisciplinary effort from several fields such as physics, mathematics, computer science, and radiation biology. Among the important parameters for an effective treatment one can include: (1) verification of the delivered dose to the tumor, (2) measurement of tumor interstitial pressure, (3) in-situ generation of oxygen and (4) real-time tracking of tumor locations. This thesis describes our work in the design and implementation of four microdevices that help the radiation oncologist achieve a more effective delivery of treatment. The first chapter is devoted to cancer terminology, treatment methodology, and the importance of the aforementioned parameters in radiation therapy. After establishing the needs of developing each of these microdevices (designed specifically to address the abovementioned parameters) in the first chapter; design criteria, fabrication processes, and experimental results of each individual microdevice will be presented in the subsequent chapters. Finally, recommendations for future work will be discussed in the last chapter. Experimental methods, test procedures, and the output characteristics of each of these micro-devices will be presented. These include a self-biased solid state radiation sensor based on resistance modulation, a magnetic tracking system composed of four planar coils for excitation and a 2-D magnetoresistive magnetic sensor, an interstitial pressure sensor using a hermitic sealed capacitive pressure sensor with an incorporated Guyton chamber, and an ultrasonically powered in situ micro oxygen generator

A batch fabricated capacitive pressure sensor with an integrated Guyton capsule for interstitial fluid pressure measurement

In this paper, we present the design, fabrication and test of a batch fabricated capacitive pressure sensor with an integrated Guyton capsule for interstitial fluid pressure measurement. The sensor is composed of 12 mu m thick single crystalline silicon membrane and a 3 mu m gap, hermetically sealed through silicon-glass anodic bonding. A novel batch scale method for creating electrical feed-throughs inside the sealed capacitor chamber is developed. The Guyton capsule consists of an array of 10 mu m diameter access holes etched onto a silicon back-plate separated from the silicon sensing membrane by a gap of 5 mu m. The presence of the Guyton capsule (i.e. plates with access holes plus the gap separating them from the sensing membrane) allows for the ingress of interstitial fluid inside the 5 mu m gap following the implantation, thus, providing an accurate measurement of interstitial fluid pressure. The fabricated sensor is 3 x 2 x 0.42 mm(3) in dimensions and has a maximum sensitivity of 10 fF mmHg(-1)

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 x 10(3) mu m(3) (19.4 pl). Functionality of the spectroscopic module of the prototype device is illustrated through the detection of H-1 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. (C) 2013 AIP Publishing LL

A Novel Electromechanical Interrogation Scheme for Implantable Passive Transponders

This paper presents design, fabrication, and implementation of a novel electromechanical energy scavenging and wireless interrogation scheme using low frequency components of musical vibrations to overcome challenges associated with previously reported passive transponders such as: short transmission range, misalignment sensitivity, and complicated receiver circuitry. The transponder has two phases of operation: 1) mechanical vibration phase, in which an acoustic receiver (a piezoelectric cantilever) converts the sound vibration into electrical power and charges a capacitor; and 2) electrical radiation phase, in which the stored charge is dumped into an LC tank, forcing it to oscillate at its natural resonance frequency and emitting the energy to an outside receiver. In a pressure sensing configuration, the distance between a planar coil and a ferrite core is modulated by the pressure, thus changing the inductance and in turn inducing a change in the frequency of the emitted signal. A prototype transponder was built and tested using a PZT cantilever with a mechanical resonant frequency of 435 Hz encapsulated in a glass capsule (length=40 mm, diameter=8 mm) along with a rectifier circuitry and a storage capacitor. The inductive pressure sensor located outside the capsule had a sensitivity of 2.5k Hz/kPa. We were able to easily pick up the transmitted RF pulses at distances of up to 7 cm without the tight requirement on alignment between the receiver and the transponder coils

A batch-fabricated laser-micromachined PDMS actuator with stamped carbon grease electrodes

In this note, we report on the development of a batch-fabricated laser-micromachined elastomeric cantilever actuator composed of a polydimethylsiloxane (PDMS) bilayer (active/inactive) and soft-lithographically patterned conductive carbon grease electrodes. The described unimorph structure has a low actuation voltage and large out-of-plane displacement. For a 4 mm long, 1 mm wide, and 80 mu m thick actuator, an out-of-plane displacement of 1.2 mm and a maximum force of 25 mu N were measured using 450 V actuation voltage

A Batch-Fabricated Single-Layer Elastomeric Actuator With Corrugated Surface

In this paper, we report on the first laser-micromachined batch-fabricated single-layer elastomeric actuator with a corrugated surface profile. The structural material of the cantilever actuator is a single [polydimethylsiloxane (PDMS)] layer, and electrodes are soft lithographically patterned conductive carbon grease. The asymmetric corrugated surface provides a bending moment in a single PDMS layer without the need for a second inactive layer. An actuator which is 5 mm long, 1 mm wide, and 80 mu m thick can generate up to 2-mm out-of-plane displacement with zero applied force and 15 mu N at zero deflection while consuming 20 mu W of static power when actuated with 500 V

Point-of-care, portable microfluidic blood analyzer system

Recent advances in MEMS technology have provided an opportunity to develop microfluidic devices with enormous potential for portable, point-of-care, low-cost medical diagnostic tools. Hand-held flow cytometers will soon be used in disease diagnosis and monitoring. Despite much interest in miniaturizing commercially available cytometers, they remain costly, bulky, and require expert operation. In this article, we report progress on the development of a battery-powered handheld blood analyzer that will quickly and automatically process a drop of whole human blood by real-time, on-chip magnetic separation of white blood cells (WBCs), fluorescence analysis of labeled WBC subsets, and counting a reproducible fraction of the red blood cells (RBCs) by light scattering. The whole blood (WB) analyzer is composed of a micro-mixer, a special branching/separation system, an optical detection system, and electronic readout circuitry. A droplet of un-processed blood is mixed with the reagents, i.e. magnetic beads and fluorescent stain in the micro-mixer. Valve-less sorting is achieved by magnetic deflection of magnetic microparticle-labeled WBC. LED excitation in combination with an avalanche photodiode (APD) detection system is used for counting fluorescent WBC subsets using several colors of immune-Qdots, while counting a reproducible fraction of red blood cells (RBC) is performed using a laser light scatting measurement with a photodiode. Optimized branching/channel width is achieved using Comsol Multi-Physics (TM) simulation. To accommodate full portability, all required power supplies (40v, +/-10V, and +3V) are provided via step-up voltage converters from one battery. A simple on-board lock-in amplifier is used to increase the sensitivity/resolution of the pulse counting circuitry

An Ocular Tack for Minimally Invasive Continuous Wireless Monitoring of Intraocular Pressure

This paper presents a novel minimally invasive implantable pressure sensing transponder for continuous wireless monitoring of intraocular pressure (IOP). The transponder was designed to make the implantation and retrieval surgery simple while still measuring the true IOP through direct hydraulic contact with the intra-ocular space. Most parts of the sensor sit externally on the sclera and only a micro-needle penetrates inside the vitreous space through pars plana. In vitro tests showed a sensitivity of 15 kHz/mmHg with about 1 mmHg resolution. In vivo tests included one month implantation in rabbits, confirming the device biocompatibility and functionality

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 mu m long with base and apex plane diameters of 500 and 300 mu m, respectively, and incorporates a laser-drilled through-hole with 44-mu m 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 x 1.3 mm x 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 mu A which, in turn, can create 0.525 mu L/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