DOW-UAP-D136, AAWSAP DIRD, Biosensors and BioMEMS: A Survey of the Present Field, March 2010

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Biosensors and BioMEMS: A Survey of the Present Field Prepared by: Acquisition Support Division (DW0-3) Defense Warning Office Directorate for Analysis Defense Intelligence Agency AAP Person 65 Administrative Note COPYRIGHT WARNING: Further dissemination of the photographs in this publication is not authorized. This product is one in a series of advanced technology reports produced in FY 2009 under t he Defense Intelligence Agency, Defense Warning Office's Advanced Aerospace Weapon System Applications (AAWSA) Program. Comments or uestions pertaining to this document should be addressed to!AAP Person 1 , AAWSA Program Manager, Defense Intelligence Agency, ATTN: CLAR/DWO-3, Bldg 6000, Washington,

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Introduction ........................................................................................................... vi What is BioMEMS? .................................................................................................. 1 Characteristics of BioMEMS ................................................................................ 2 Categories of BioMEMS ....................................................................................... 3 Brain-Implanted BioMEMS Micromachine Neuroelectrodes ................................ 4 BioMEMS Implantable Sensors ............................................................................. 10 MEMS Blood Glucose Sensors ............................................................................... 13 Commercial Blood Glucose Sensors .................................................................. 14 Enzyme-Based Biosensors................................................................................ 14 Thermopile Implantable Glucose Sensors ........................................................ 15 Neuroengineering by BioMEMS............................................................................. 20 Bioelectric Events............................................................................................. 20 Bionics and Neurointerfaces................................................................................. 22 Bioelectrodes and BioMEMS ............................................................................. 22 Microelectrode Array Fabrication ..................................................................... 24 Polymer BioMEMS Electrodes ........................................................................... 26 Retinal Devices Using BioMEMS........................................................................ 27 Microscale in Therapeutic Neurostimulation..................................................... 30 MEMS in Microfluidics........................................................................................... 32

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NASA Space Applications for Microfluidic Systems ........................................... 34 Microcantilever MEMs Sensors ............................................................................. 36 Figure 1. Varieties of BioMEMS and Sensors........................................................... 2 Figure 2. Functional MEMS Micromachines Attached to Sensing Bioelectrodes....... 5 Figure 3. Schematic Diagram of a MEMS Motor Complete With a Method of Converting Oscillatory Motion to Linear Motion ....................................... 5 Figure 4. Illustration of the Basic Physical Principle of the BioMEMS Motor ........... 6 Figure 5. Close-up Views of the Micro-Motor Gear .................................................. 6 Figure 6. An Insulin MEMS Pump............................................................................ 8 Figure 7. An ISFET (Ion Sensitive Field Effect Transistor) Needle-Type pH Sensor for Monitoring Tissue Physiologic Status ............................................... 11 Figure 9. Control of an Insulin-Delivery System by an Implantable Glucose Figure 11. An Experimental MEMS Blood Glucose Sensor ..................................... 15 Figure 14. Illustration of the Thermocouple Principle .......................................... 18 Figure 15. Thermopile Glucose Sensor (left) With Functional Illustration (right) are Made Using Photolithographic Techniques .................................... 19 Figure 16. Photograph and Illustration of the Thermopile Glucose Sensor in a Figure 17. A MEMS Biopotential Electrode System................................................ 20 Figure 18. A Neural Cell Showing Dendritic Inter-Connections That are Electrically Active With Other Cells........................................................................ 21 Figure 20. Scanning Electron Micrograph of a Brain Electrode Array Manufactured From Titanium and Produced by a Process of Electrodischarge Figure 21. Scanning Electron Micrograph of a 1141 Electrode Array Made to Be Inserted Into the Surface of the Human Brain .................................... 25 Figure 22. Polymer Based Cortical Penetrating Neuroelectrodes Made by Processes of Thin Film Deposition and RF Etching ............................................... 26 Figure 23. A MEMS Microelectrode Array Implanted Into the Cortex of a Rat Brain Figure 24. A Representation of the Retinal Prosthesis ......................................... 28 Figure 25. A BioMEMS Fabricated 4x4 Microelectrode Retinal Array..................... 28 Figure 26. An Illustration of the Retinal Neuroprosthesis Created by the Boston Figure 27. Power Transfer by Magnetic Induction to an Implanted BioMEMS Retinal Figure 28. A New Generation of Implantable Neurostimulation Devices Can Pass Through the Lumen of a Syringe Needle.............................................. 31 Figure 29. Illustration of the Internal Construction of the Ultrasound Powered Neurostimulator Developed at ASU ..................................................... 32

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Figure 30. Microfluidics in Glass........................................................................... 32 Figure 31. Commercial Lab-Chip Devices That Allow Analysis for Biomarkers of Various Diseases Using On-Chip Electrophoresis in Microscale........... 34 Figure 32. Design of an Automated Cell Culture System for NASA Space Applications Incorporating Microfluidics and Integrated Optical Figure 33. NASA Space Application of Microfluidic Cell Culture System Made by Figure 34. Principle of a Microcantilever That Bends When It is Loaded With an Figure 35. Scanning Electron Micrograph Showing a Cantilever Beam With a Single Vaccinia Virus Particle ......................................................................... 38 Figure 36. Antibodies Attached to a Cantilever Array Create Different Specificities to Substances in Blood That are Indicative of Cancer.......................... 38

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Biosensors and BioMEMS: A Survey of the Present Field Biomedical sensors and implantable devices employing micro­ electromechanical technology will be important to the future of biomedicine. Once just science fiction, the notion of a bionic man is now becoming a reality through the application of microscale technologies. Today it is not unusual to have a friend or family member who has an implantable device, such as a pacemaker, defibrillator, cochlear implant, biosensor, neurostimulator, or insulin pump. We have only seen the beginning of this technology development, and today's state-of-the-art implantable devices will be seen as crude and cumbersome tomorrow. With the rapid pace of development, it is probable that within the next two decades we will have as many medical treatments based on microdevices as there are pharmaceutical solutions today. This paper examines some of the most recent advances in the field, as well as the technologies that are likely to appear in the next few years.

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What is BioM EMS? BioMEMS stands for biomedical micro-_glectro-mechanical ~ystems. It is a name applied to biological and medical devices that are created using advanced fabrication processes that allow the devices to be very small relative to comparable devices produced by traditional techniques. BioMEMS devices can also exploit the microscale to provide new functions that are not practical or possible in large-scale devices. The name applies to an exceptionally wide variety of engineered devices that derive from electrical, mechanical, chemical, and molecular engineering. The name distinguishes these from nanoMEMS which are submicron in scale such as carbon nanotube structures. Recently BioMEMS has become something of a misnomer as many of the latest technologies are being designed and developed based on nanoscale technologies which are many times smaller than microscale technologies. While current devices are manufactured mostly on the microscale, many of the functioning parts and the materials they operate on are at the nanoscale level. NanoMEMS for biomedical applications are mostly carbon-based materials that have emerged as prime materials because of their favorable mechanical and electrical properties. Carbon-based nanostructures such as graphene exhibit a high Young's modulus (stiffness), high strength, low density, low friction and large surface area. The