MEMs for Biomedical Applications

MEMS for Biomedical ApplicationsReporter: AGNES PurwidyantriStudent ID no: D0228005

Biomedical Engineering Dept.

What are MEMS? [1]Micro-Electro-Mechanical Systems (MEMS) is the integration of mechanical elements, sensors, actuators, and electronics on a common silicon substrate through microfabrication technology.Microfabrication of silicon-based structures is usually achieved by repeating sequences of photolithography, etching, and deposition stepsMicroelectronics fabrication techniques routinely produce well-controlled features that range in size from millimeters to submicrometers, while soft lithography techniques were recently used to produce features below 100 nm.

MEMS ApplicationsAccelerometers (Inertial Sensors Crash Bags, Navigation, Safety)Ink Jet Print Heads Micro Fluidic PumpsInsulin Pump (drug delivery) Pressure SensorAuto and Bio applicationsSpatial Light Modulators (SLMs)MOEM Micro Optical Electro Mechanical SystemsDMD Digital Mirror DeviceDM Deformable MirrorChem Lab on a ChipHomeland securityRF (Radio Frequency) MEMSLow insertion loss switches (High Frequency)Mass Storage Devices

3The list goes onMEMS vs IC

Typical process flow for IC manufacturing. [2] Differences with MEMS manufacturing are in bold italicsExample of MEMS Devices:

DLP (Digital Light Processor) (Texas Instruments) Light Modulating chip>100000 individually addressable micromirrors (10 x 10 m2)Binary tilting0.8 m CMOS SRAM on the subs, beneath mirror layers

InkJet Laser Printer

The Accelerometer1987 TRW NovaSensor Accelerometer First generation inertial sensor Poppy seed is on top to show scale.

Analog Devices 1993 Saab was the first automobile company to include MEMS accelerometers to trigger airbags.

Combined standard CMOS technology with MEMS fabrication

MEMS-based systems answered the call of government regulated passive restraints in automobiles where these systems sensed rapid deceleration and in the event of a collision sent a signal to inflate rapidly an airbag.6First generation inertial sensor TRW Lucas Nova Sensor 1987Poppy seed is on top to show scale.

Combined standard CMOS technology with MEMS fabrication

MEMS-based systems answered the call of government regulated passive restraints in automobiles where these systems sensed rapid deceleration and in the event of a collision sent a signal to inflate rapidly an airbag.Micro MachinesSurface Micromachining takes off in the 1990s. (Sandia National Laboratories)

This basically consists of alternating layers of structural materials (poly crystalline silicon) and sacrificial layers (Silicon Dioxide). The sacrificial layer is a scaffold and acts as a temporary support and spacing material. The last step of the process is the release step, where the sacrificial layer is removed freeing the structural layers so they can move.7Surface micromachining leverage standard CMOS fabrication process technology (CMOS Complimentary Metal Oxide Semiconductor, a silicon based semiconductor standard process).

This basically consists of alternating layers of structural materials (poly crystalline silicon) and sacrificial layers (Silicon Dioxide). The sacrificial layer is a scaffold and acts as a temporary support and spacing material. The last step of the process is the release step, where the sacrificial layer is removed freeing the structural layers so they can move.

Surface micromachining started out in Berkeley in the late 80s. DARPA supported the MUMPS program starting in 1992 (Multi User MEMS Projects) at MCNC (Microelectronics Center of North Carolina)

MOEMsMicro Optical Electro Mechanical SystemsMEMS or Microsystems have the potential of having a greater impact on global business and society than did the computer chip. - TIDevelopment started 1980s, first commercial product - 1996

8TI started the development of DMDs in the mid 1980s. In 1996 the first commercial product was released. It is estimated by some that TIs investment was on the order of $1 Billion. Today they command over $400M in revenue/yr projected to grow from $800M to $1.8B between 2005 and 2010.

Other applications under MOEMS include:DM Deformable Mirror technology (AgilOptics)GLV Grating Light Valve (Silicon Light Machines and Sony)Switching systems for telecommunications applicationsMicro NeedlesMEMS needle within the opening of a small hypodermic needleSmaller size reduces pain and tissue damage now there are much smaller MEMS needle arrays.The plastic needle array is made through a standard MEMS fabrication process to make the molds, micro injection process is used to create the arrays.

Procter and GamblePlastic Needle Array9Smaller size reduces pain and tissue damage now there are much smaller MEMS needle arrays.

The plastic needle array is made through a standard MEMS fabrication process to make the molds, micro injection process is used to create the arrays.

Additional Applications of MOEMS

10AgilOptic (formally Intellite) is an Albuquerque based company producing DMs (deformable mirrors). These are used for image enhancement (taking out wavefront distortion of images which occur due to atmospheric disturbances, also when image the retina of the eye and adjusting focus as a laser welding beam goes through a plum of hot gas). The telecon boom infused a lot of capital and R&D money into MOEMS, but the telecon bust resulted in giving MEMS a bad name, for a short period of time.BioMEMS The Overlap between microbiology and microsystem feature sizes makes integration between the two possibleAtom100 m10 m1 m0.1 m0.01 m0.001 m(1 nm)Eukaryotic cellsProteinsVirusesBacteriaRibosomeNucleusGate of Leading Edge TransistorVisible LightSurface Micromachining Features (MEMS)Molecules(10 nm)11Bio-base scale.MEMS for Biomedical ApplicationsLab on a chip/ smart prosthesisAdvantages:BiocompatabilityGreater reproducibility+reliabilityMiniaturized implantsRapidAbility to provide electrical stimulusChemical functionalization (tissue eng)MiniaturizedLow costIntegration of sensor, actuators and electronicsInteraction with fluids (microfluidics TAS, biochemical sensors)etcDevices Categories A large variety difficult to classify Patient viewpoint: diagnostic microsystems: rapid point-of-care, systems on a chip, cell and molecule sorting, DNA diagnostics surgical microsystems: MIS (minimally invasive surgery), CADassisted surgery - microrobotics therapeutic microsystems + prostheses: drug and gene delivery, tissue augmentation/repair, biocapsules, micro/minimally invasive surgical systems The scale of the application: body level (drug delivery, tools for microsurgery, pacemakers, neural probes), analysis of body fluids (Lab-on-a-chip for blood analysis, glucose monitoring, electrophoresis), tissue and cell analysis, genomics (DNA microarrays) and proteomics (protein identification and characterization) Biggest promise: better outcome for the patient and a lower overall health and costMicrofluidic Devices

Microactuators

Micropumps

Phase-change Micropump

Piezoelectric Micropump

Applications of Micro SystemsMicro Total Analysis SystemMicro ELISAMicro FACSMicro mass-spectrometer

Micro Biomedical SystemMicro syringeMicro CSF shuntDrug delivery bio-chipImmunosensing bio-chipMicro cell chip

Micro-ELISA

Micro Mass Spectrometer

Micro Shunt System

MEMS cantilevers as biosensors [3]Drug Delivery Bio-chip

Micro cell chip

Detection of Single DNA [4]

By changing the coating (Nano) one can functionalize the cantilever to detect single strands of DNA.Mass resolution is on the order of under 1 ato gram (10-18grams)

Gold dot = 40nmSiN thickness = 90nm26Enumeration of Single DNA Molecules Bound to aNanomechanical OscillatorBojan IlicResonant nanoelectromechanical systems (NEMS) are being actively investigated as sensitive mass detectorsfor applications such as chemical and biological sensing. We demonstrate that highly uniform arrays ofnanomechanical resonators can be used to detect the binding of individual DNA molecules through resonantfrequency shifts resulting from the added mass of bound analyte. Localized binding sites created with goldnanodots create a calibrated response with sufficient sensitivity and accuracy to count small numbers of boundmolecules. The amount of nonspecifically bound material from solution, a fundamental issue in any ultrasensitiveassay, was measured to be less than the mass of one DNA molecule, allowing us to detect a single1587 bp DNA molecule.The drive toward ultra-sensitive biochemical assays has motivated significant efforts in single moleculedetection and identification. Resonant nanomechanical devices [1-3] provide an alternative approach totechniques such as those using fluorescent labels. The mechanical approaches also have the possibility ofquantification of the bound molecules, and can be incorporated in array-based systems for multiplexedbiochemical analyses. Carbon nanotubes, attractive because of their uniform diameters and small mass havealso been considered as biomolecular detectors, but remain difficult to incorporate in device architectures andhave not yet been able to quantify specifically bound biomolecules.We have detected the binding of functionalized 1578 base pair long double-stranded deoxyribonucleic acid(dsDNA) molecules to nanomechanical oscillators by measuring the resonant frequency shift due to the addedmass of the bound molecules. The binding of a single DNA molecule could readily be detected [4]. Theresonant frequency of individual oscillators in an array of resonator devices was measured by thermo-opticallydriving the individual devices and detecting their motion by optical interference. The number of boundmolecules on each device was quantified as proportional to the measured frequency shift with a proportionalityconstant determined experimentally and verified by modeling of the mechanical response of the system. For thesmallest and most sensitive cantilevers the mass sensitivity was 194Hz/attogram. The resonant frequency shiftof the oscillators can be measured with high accuracy, having a practical experimental uncertainty of ~10 Hzcorresponding to ~0.05ag. The nonspecific binding of material to the oscillator throughout the process,however, limits the quantification of the specifically bound compounds for a particular analytical process. Wemeasured the effects of non-specific binding of material other than the DNA from our solutions and found thisto be approximately 0.43 0.23ag for an oscillator of length L=3.5microns, with 0.23ag therefore being theapproximate limiting mass resolution resulting from uncontrolled binding to the surface in our particularprocess. For the smallest (L=3.5micron), most sensitive oscillator this mass uncertainty corresponds to the massof ~0.26 DNA molecules, enabling us to be able to resolve a single molecule. With the most sensitive devicesand dilute DNA concentrations, we have detected a single dsDNA molecule.

Figure 1: Micrographs (a & b) showing arrays of cantilevers of varying lengths. (c) SEM of the 90nm thick SiNcantilever with a 40nm circular Au dot.Figure 2: Schematic of the optical measurement setup and binding strategy of the thiolated dsDNA moleculesto the Au dots.Figure 3: Frequency spectra before and after the binding events show a frequency shift due to a single dsDNAmolecule bound to the Au surface of the cantilever.References:[1] "Nanoelectromechanical Systems", H. G. Craighead, Science, 290, 1532-1535 (2000).PART 1: Page 2 of 3http://www.hgc.cornell.edu/Nems%20Folder/Enumeration%20of%20Single%20DNA.html 8/22/2006[2] "Mechanical Resonant Immunospecific Biological Detector", B. Ilic, D. Czaplewski, H. G. Craighead,P. Neuzil, C. Campagnolo and C. Batt, Applied Physics Letters, 77, 450-452 (2000).[3] N. V. Lavrik, M. J. Sepaniak and P. G. Datskos, Rev. Sci. Inst. 75, 2229 (2004).[4] "Enumeration of DNA Molecules Bound to a Nanomechanical Oscillator", B. Ilic, Y. Yang, K. Aubin,R. Reichenbach, S. Krylov, and H. G. Craighead, Nano Letters, 5, 925-929 (2005).

Resonance Shift [5]

5 x 15um Cantilever with anE. Coli cell bound to immobilizedantibody layer.Black is the response before cell attachment,Red is after cell attachment.School of Applied and Engineering Physics and the Nanobiotechnology Center, Cornell University

Cantilever based-biosensor in CMOS Technology[6]

Origin of nanomechanical cantilever motion generated from biomolecular interactions:MEMS cantilevers as biosensors

Bio-MEMS Polymer/Si Cantilevers Sensors [7] Grayson A.C. R et al. 2004. A BioMEMS Review: MEMS Technology for Physiologically Integrated Devices. Invited Paper. IEEE Proceeding 92 (1).Vemal, R., Lo, C., Ong, S., Lee, B. S and Yong, C. C. 2009. MEMS vs. IC Manufacturing: Is Integration Between Processes Possible.1st Int'l Symposium on Quality Electronic Design-Asia. IEEE 2009Hubler, U et al. 2003. Reprint from BioWorldhttp://www.hgc.cornell.edu/Nems%20Folder/Enumeration%20of%20Single%20DNA.htmlhttp://www.news.cornell.edu/releases/April04/attograms.ws.html Kristein, K. U et al. Cantilever-Based Biosensors in CMOS Technology. Physical Electronics Laboratory, ETH Zurich, Switzerland.Hit, Z. et al. 2002. Applied Physics Letters 81 (16): 3091-3093.

ReferencesThank You