bio medical applications of mems

8/2/2019 Bio Medical Applications of Mems

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BIOMEDICAL APPLICATIONS OF MEMS

ABSTRACT:MEMS technologies can be used to produce complex electrical,

mechanical, fluidic, thermal, optical, and magnetic structures, devices, andsystems on a scale ranging from organs to sub cellular organelles. This

miniaturization ability has enabled MEMS to be applied in many areas of

biology, medicine, and biomedical engineering a field generally referred to as

Bio MEMS. The future looks bright for Bio MEMS to realize (1) micro sensor

arrays that act as an electronic nose or tongue, (2) micro fabricated neural

systems capable of controlling motor or sensory prosthetic devices, (3) painless

microsurgical tools, and (4) complete micro fluidic systems for total chemical or

genetic analyses.

INTRODUCTION:Micro electromechanical systems (MEMS) is a technology of

miniaturization that has been largely adopted from the integrated circuit (IC)industry and applied to the miniaturization of all systems Miniaturization is

accomplished with micro fabrication processes, such as micromachining, that

typically use lithography, although other non-lithographic precision micro

fabrication techniques exist (FIB, EDM, laser machining). Due to the enormous

breadth and diversity of the field of MEMS, the acronym is not a particularlyapt one. However, it is used almost universally to refer to the entire field. Othernames for this general field include micro systems, popular in Europe, and

micromachines, popular in Asia.MICROFABRICATION:

Although many of the micro fabrication techniques and materials used

to produce MEMS have been borrowed from the IC industry, the field ofMEMS has also driven the development and refinement of other micro

fabrication processes and non-traditional materials.

Conventional IC Processes and Materials:Photolithography; thermal oxidation; do pant diffusion; ion

implantation, LPCVD; PECVD; evaporation; sputtering; wet etching; plasma

etching; reactive-ion etching; ion milling silicon; silicon dioxide; silicon nitride;aluminium.

Additional Processes and Materials used in MEMS:Anisotropic wet etching of single-crystal silicon; deep reactive-ion

etching or DRIE; x-ray lithography; electroplating; low-stress LPCVD films;

thick-film resist (SU-8); spin casting; micro moulding; batch micro assemblypiezoelectric films such as PZT; magnetic films such as Ni, Fe, Co, and rare

earth alloys; high temperature materials such as SiC and ceramics; mechanically

robust aluminium alloys; stainless steel; platinum; gold; sheet glass; plastics

such as PVC and PDMS.The methods used to integrate multiple patternedmaterials together to fabricate a completed MEMS device are just as important


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as the individual processes and materials themselves. The two most general

methods of MEMS integration are described in the next two sub-sections:

Surface micro machining and bulk micro machining.

Surface Micro machining:

Simply stated, surface micromachining is a method of producingMEMS by depositing, patterning, and etching a sequence of thin films, typically~1 m thick. One of the most important processing steps that are required of

dynamic MEMS devices is the selective removal of an underlying film, referred

to as a sacrificial layer, without attacking an overlaying film, referred to as the

structural layer, used to create the mechanical parts. Surface micromachining

has been used to produce a wide variety of MEMS devices for many different

applications. In fact, some of them are produced commercially in large volumes

(> million parts per month).

Bulk Micromachining:Bulk micromachining differs from surface micromachining in that the

substrate material, which is typically single-crystal silicon, is patterned andshaped to form an important functional component of the resulting device (i.e.,

the silicon substrate does not simply act as a rigid mechanical base as is

typically the case for surface micromachining). Exploiting the predictable

anisotropic etching characteristics of single-crystal silicon, many high precision

complex 3-D shapes, such as V-grooves, channels, pyramidal pits, membranes,via, and nozzles, can be formed {111 Planes}.

Substrate Bonding:

Silicon, glass, metal and polymeric substrates can be bonded togetherthrough a variety of processes (i.e., fusion bonding, anodic bonding, eutectic

bonding, and adhesive bonding). Typically at least one of the bonded substrates

has been previously micro machined. Substrate bonding is typically done toachieve a structure that is difficult to form otherwise (i.e., large cavities that

may be hermetically sealed or a complex system of enclosed channels) or

simply to add mechanical support and protection.

Non-Silicon Micro fabrication:The development of MEMS has contributed significantly to the

improvement of non-silicon micro fabrication techniques. Two prominentexamples are LIGA and plastic moulding from micro machined substrates.

LIGA:LIGA is a German acronym standing for lithography,

galvanoformung (plating), and abformung (moulding). However, in practice

LIGA essentially stands for a process that combines extremely thick-film resists(often >1 mm) and x-ray lithography, which can pattern thick resists with high

fidelity and results in vertical sidewalls. Although some applications may

require only the tall patterned resist structures themselves, other applications

benefit from using the thick resist structures as plating moulds (i.e., material canbe quickly deposited into the mould by electroplating). A drawback to LIGA is


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the need for high-energy x-ray sources (e.g., synchrotrons or linear accelerators)

that are very expensive and rare (i.e., only several such sources exist in the

U.S.).

SU-8:

Recently a cheap alternative to LIGA, with nearly the sameperformance, has been developed. The solution is to use a special epoxy-resin-

based optical resist, called SU-8, that can be spun on in thicklayers (>500 m),

patterned with commonly available contract lithography tools, and yet still

achieves vertical sidewalls.

Plastic Moulding with PDMS:Poly dimethylsiloxane (PDMS) is a transparent elastomeric that can

be poured over a mould (e.g., a wafer with a pattern of tall SU-8 structures),

polymerized, and then removed simply by peeling it off of the mould substrate.

The advantages of this process include (1) many inexpensive PDMS parts can

be fabricated from a single mould; (2) the PDMS will faithfully reproduce even

sub-micron features in the mould, (3) PDMS is biocompatible and thus can beused in a variety of Bio MEMS applications, and (4) since PDMS is transparent,

tissues, cells, and other materials can be easily imaged through it.

Common uses of PDMS in biomedical applications include: micro stamping

of biological compounds (to observe geometric behaviour of cells and tissues)

and Micro fluidics systems.

BIOMEDICAL MICROSENSORS:The majority of MEMS used in biomedical applications act as

sensors. Examples include critical sensors used during surgery (i.e., measuringintravascular blood pressure), long-term sensors for prosthetic devices, and

highly sophisticated sensor arrays for rapid lab-quality diagnosis at home.

Micro sensors for Biomechanics:Studies of the forces created by and imposed on the body benefit from

increasing the sensitivity of mechanical stress and strain sensors while also

reducing their size and cost. The following are examples of micro sensors used

to study biomechanics.


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Strain Gauges:Strain gauges are used to characterize the forces in the body. Since

silicon is known to be an excellentpiezo resistive material (i.e., its resistance

changesas a function of applied force), it can be easilymicro machined to form

sub- milli meter multi-axisstrain gauges [10]. Applications of such miniaturizedstrain gauges include orthopaedic research and thestudy of muscles. Although

the understanding of muscle function and structure is well understood at the

whole-muscle and cellular levels, muscles have not been well characterized in

the region in between. An improved understanding at this level would allow for

the development of improved locomotiontherapies and prosthetic devices.

Accelerometers:One class of micro sensors that MEMS technology has had the most

positive impact on are inertial sensors (i.e., accelerometers and gyros). Since

inertial devices typically consist of a proof mass, mechanical flexure, and

displacement sensor, MEMS technology is well suited to integrate each of these

sensor elements into a single chip. In fact, it is also possible to integrate ICswith the micromechanical elements to add signal amplification and filtration

capability to the chip-scale sensor. Inertial micro sensors are useful to

determine impact level and patient posture.

Micro sensors for Pneumatic Bio systems:Since much of the human body is a complex system of pumps, valves,

vessels, and interconnects, pressure in many parts of the body is an important

parameter to indicate the health and well being of a patient. Pressure sensors are

used in medicine in many applications: blood pressure, bladder pressure, andcerebral spinal fluid pressure to name a few. In addition to performance

requirements, the size of pressure sensors, particularly those inserted into the

body must be small and ideally disposable. MEMS technology is wellpositioned to deliver solutions to this opportunity. In fact, a good example is the

commercially successful low-cost disposable medical pressure sensor developed

by Lucas Nova Sensor NPC-107. In it a silicon micro machined sensing element

is used to meet or exceed all industry requirements (e.g., sensitivity within +/-

1% and linearity better than 1%). Another micro machined silicon pressure

sensor produced by NovaSensor is made small enough (1 mm x 0.7 mm x 0.175mm thick) to be inserted into a catheter and inserted into arteries.

Micro sensors for Chemical Bio systems:Since living organisms are extremely sophisticated chemical

processing systems, there are many biomedical applications for chemical

sensors (e.g., medical diagnostic instruments, drug screening, implantablesensors for prostheses, and environment monitoring). Although the

micromachining of chemical sensors is typically simple, other components

sometimes used in a complete chemical sensor system (i.e., sample preparation

and delivery, reaction control, and waste disposal) are more difficult to integratetogether.


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Impedance Sensors:The conductivity of some materials is affected by the presence and

relative concentration of certain gasser vapours. Examples of these materials

include polymers doped with conductive particles, conductive polymers, and

some metal oxides. The challenges common to impedance-based chemicalsensors include identifying single gases, quantifyinggas concentration, dealing

with gas mixtures, sensitivity to water vapour, sensitivity to temperature

changes, and micro fabrication of arrays of uniquelysensitive sensors.

Polymer-Based Gas SensorsMany polymers will geometrically swell reversibly when exposed to

certain gases. Conductive polymers, such as polypyrrole, can be used directly as

a viable chemiresistor. To use insulating polymers, they are doped with

conductive particles to reduce their impedance (e.g., carbon black). When

doped, the overall resistance of the doped polymer will change as a function of

the chemically specific and concentration-dependent swelling. One difficulty is

that the polymers will swell to a greater or lesser extent when exposed to avariety of gases. To identify specific gases, the response pattern of many

different polymers is needed. In addition to resistive measurements of geometric

swelling, configurations that capacitively detect swelling have also been used.

In these sensors the insulating polymers are not doped. Since it is known that

certain diseases cause the body to generate specific gases that are not normallypresent, gas sensors have been used to help diagnose patient health. In order to

micro fabricate arrays of sensors with unique polymers, the integration process

must contend with the large volume of solvent that is typically present duringpolymer deposition. Furthermore, the micro fabrication technique must not

damage previously deposited polymers. One strategy is to use a removable

mask to selectively deposit each polymer into a specific area. This techniquehas difficulty forming sub-milli meter sensors due to poor adhesion to the

substrate when the mask is removed (i.e., the polymers adhere more strongly to

the mask than to the substrate). Another strategy is to use a permanent micro

well structure to contain the polymer-solvent solution in a well-defined sub-

milli meter area without disturbing previously deposited polymers.

Metal oxides:The conductivity of certain metal oxides, most commonly SnO2, is

known to vary as a function of the concentration of specific gasses (e.g., O2,

H2, CO, CO2, NO2, and H2S) when the metal oxide is heated sufficiently to

induce a chemical reaction that is detected. There are several mechanisms that

cause the resistance of the metal oxide to vary. The micro fabrication of thesesensors can be relatively straightforward, unless additional micro machined

features are added to improve sensor response and power consumption (i.e.,

integrating micro fabricated heaters, thermal isolation structures (e.g.,

membranes) that require far less power to heat, and CMOS signal detection,amplification, and filtering circuitry.


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Electrochemical Sensors:The oxidation and reduction of chemical species on a conducting

electrode can be observed by measuring the movement of charge. There are two

primary methods of sensing electro chemical reactions:

Potentiometric and amperometric.

Potentiometric sensors can be used to measure the equilibrium potential

established between the electrode material and the solution, a potential that isdependent on the chemistry involved. Amperometric sensors measure the

current generated by a reaction and thus give a measure of reaction rates. By

controlling the potential of the electrode relative to the solution and measuring

the charge flow induced, the presence of specific ions can be determined by

observing the potential at which they undergo oxidation or reduction. This is a

process known as voltammetry.Micromachining processes can be used to accurately and reliable

define the area, number, and relative position of electrodes that are exposed to

solution. In addition, the simple construction of a typical electrochemical sensor

(i.e., a partially insulated metal trace on a substrate) allows ICs to be easily

integrated with the electrode. The ICs can be used to provide on-chip signal

processing and amplification.


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Molecular-Specific Sensors:Chemical sensors that respond only to certain ions or molecules can

be extremely selective. Among the most selective are the interactions between

complex organic molecules, such as antigens and antibodies. One caveat is that

often very selective sensors are also less reversible and thus may require specialpackaging to protect the sensors until they are needed. A prominent example of

a molecularly sensitive amperometric sensor is one that uses a glucose oxidase

enzyme to detect glucose. The enzyme, which is typically immobilized on or

near electrodes, reacts with glucose and alters the local pH, oxygen

concentration, and hydrogen peroxide concentration events that can be

electrochemically detected.

ISFETs:Field effect transistors (FETs) are very sensitive to variations in the

amount of charge on their controlling electrodes (i.e., gate). If an ionic solution

acts as the gate of a FET, the device will be tremendously sensitive to the

overall ion concentration of the solution (i.e., not selective to specific ions). Agood pH sensor can be made this way and indeed one exists. By coating the gate

of the FET with a compound that will selectively bind or allow to pass only

specific ions or molecules, an ion-sensitive FET, or ISFET, can be realized.

Common difficulties with ISFETs, as with all chemical sensors, are drift and

repeatability.

Resonant Sensors:The resonant frequency of a mechanical element is strongly

dependent on its geometry, mechanical properties, and mass. By coating aresonating mechanical element, such as a beam or membrane, with a compound

that will selectively bind to only specific ions or molecules, the mass of the

mechanical element will increase with their concentration. The ion-concentration dependent mass loading can be determined by measuring the

corresponding shift in the resonant frequency. The most common resonant

chemical sensors use acoustic waves driven along surfaces of a solid (i.e.,

surface acoustic waves, SAW) or in a thin membrane (i.e., flexural plate waves,

FPW). Acoustic-wave sensors have been used to detect liquid density, viscosity,

specific gas vapours. Design challenges include (1) temperature sensitivity ofthe mechanical flexure, (2) selectivity of the binding compound, and (3)

reversibility of the binding and mass loading process. MEMS technology

impacts resonant chemical gas sensors by allowing miniature sensors to be

produced at low cost.

Cell-Based Sensors:An innovative micro sensor uses a cell as the primary transduction

mechanism. An advantage of using cells to detect chemicals is that cells are

microscopic chemical laboratories that can amplify a chemical signal (i.e., the

detection a few molecules can lead to the production of many so called secondmessenger molecules) essentially biological gain. The amplified cell signal


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can be monitored by either detecting a chemical change within the cell or

inferring the change by monitoring other parameters, such the electrical activity.

One sensor uses chick myocardial cells to detect the presence of epinephrine,

verapamil, and tetrodotoxin in the cell environment. Limitations of cell-based

sensors include the lifetime and robustness of the cells.Micro sensors for Electrical Bio systems:

The central and peripheral nervous systems are the primary electrical

bio systems of interest. Many sensors and probes have been used to measure the

electrical signals generated by neural tissue. Example includes

electrocardiogram (ECG), electroencephalogram (EEG), electro neurogram

(ENG), electro myogram (EMG), and electro retinogram (ERG). These

bioelectrical signals are typically transuded with either external or internal

electrodes. With MEMS technology, many electrodes can be co-fabricated onto

a single substrate so that both precise temporal and spatial information can be

obtained. MEMS technology can also be used to shape the substrate into either

arrays of microprobes capable of penetrating neural tissue or into a perforatedmembrane through which regenerating neural tissue can grow and then be

monitored. In the U.S. the University of Michigan, Stanford University, and the

University of Utah have spent years developing and improving various MEMS-

based neural electronic interfaces. Micro fabricated silicon neural probe arrays.

Top: Close-up of the probes and electrodes. The implications of MEMStechnologies for neuroscience are revolutionary. We now have the potential to

develop arrays of micro systems, which can be tailored to the physical and

temporal dimensions of individual cells. Neuroscientists can now realisticallyenvision sensing devices that allow real-time measurements at the cellular level.

Information from such sensors could be monitored, analyzed, and used as a

basis of experimental or medical intervention, again at a cellular level. Anotherexample is the use of micro machined neural sensors and stimulators to control

prosthetic limbs with processed signals recorded from the brain or spinal

column.

BIOMEDICAL MICROACTUATORS:Micro actuators are useful in biomedical applications when biological

objects or their environment need to be controlled on the microscopic scale.Furthermore, the ability to integrate many micro actuators as easily as only one

makes it feasible to produce complex micro systems capable of controlling

many parameters.

Micromanipulators:To manipulate cells, tissues, and other biological objects, micro

manipulators must be driven by a micro actuation mechanism capable of

operating in a conductive solution. Good candidates include magnetic,

pneumatic, thermal, and shape-memory alloy actuation. The magnetic micro

actuator shown in has been used to manipulate single-cell protozoa in saline.


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The shape memory alloy Micro actuator is capable of grasping tissues during

endoscopic surgical procedure.

A second generation device constructed with polymers is being commercialized

by Micrus, Inc. and is presently in human trials. Magnetic micro actuator

manipulating a Single - cell Protozoa. Surgical micro gripper actuated by shapememory- alloy forces.

Surgical Micro instruments:The capability of most micro actuators to surgically interact with

biological tissues is hindered by their inability to withstand forces on the scale

of ~1 mN. The most successful uses of micro actuation in surgical devicesemploy high-force small displacement stepper motors or resonant micro

structures. MEMS technology can be used to add a variety of capabilities to

surgical micro instruments (e.g., micro heaters, micro sensors, fluid delivery,

fluid extraction, feedback and control). A scalpel driven by a piezoelectricmicro actuator is an innovative example of using MEMS technology in surgicaltools. The piezoelectric stepper motor allows the position the scalpel to be

precisely controlled. By integrating an ability to measure the stresses

experienced by the scalpel during cutting, the actual cutting force can be

quantified and controlled. Piezo electrically driven force sensitive Scalpel. An

ultrasonic cutting tool fabricated by bulk micro machining is another good

example of using MEMS technology in surgical devices.


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Again, piezoelectric material is attached to the cutter to resonate the tip of thetool at ultrasonic frequencies. Only when activated will the device easily and

rapidly cut through even tough tissues (e.g., the hardened lenses of patients withcataracts). The devices include an imbedded Micro channel through which fluid

and surgical debris can be extracted while cutting. Micro pumps, and Micro

valves,Micro filters, and Micro needles Clearly the need to precisely control

gas and fluid flow is critical for diagnostic, surgical, and therapeutic biomedical

systems. With this as motivation, there have been many efforts to developviable reliable low-cost high-precision micro needles, micro filters, micro

valves and micro pumps.Micro needles:

The reduction in pain caused by needle insertion is important for

patient satisfaction and health. This is particularly true for patients suffering

from diabetes who inject themselves with insulin at least a few times a day. It isthen no surprise that the smallest needles presently available are the 30-gauge

needles used by diabetes. Micromachining and MEMS technology has been

used to produce silicon micro needles that are much sharper than existing

needles. Smallest conventional needle (30 gauge). Micro fabricated siliconneedle. The size scale of both images is the same.Micro filters:

The process used to produce conventional filters capable of screening

micron scale objects results in an unacceptably broad statistical distribution of

the size of objects that can pass. Micromachining and MEMS technology has

been used to realize filters that are precisely and uniformly machined, which

greatly reduces the statistical variation in objects that pass through.

Micro valves:Several different types of micro valves have been Micro fabricated,

including normally-open and normally-closed valves either for controlling


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gasses or fluids. A complete discussion of the specifics involved in the

development of each valve type is beyond the scope of this paper.

Instead, the options and trade-offs of valve design in general will be described.

A leader in the commercialization of micro valves has been Redwood

Microsystems of Menlo Park, CA. They have designed many different valves,

but each has many common characteristics. First off, the actuation mechanismused in each valve is the samea small quantity of inert fluid is heated with an

integrated resistor until a phase change is induced that exerts a tremendous

force. Although the micro fabrication process that precisely traps a fluid inside a

micro cavity is not trivial, it can be commercialized. The performance of micro

valves compares favourably with macroscopic solenoid valves. In particular,micro valves typically operate faster and have a longer operational lifetime than

macro-scale valves.

The TiNi Corporation has also commercialized a micro machinedpressure sensor driven by shape memory alloys. HP and NovaSensor have

designed, fabricated, and tested micro valves driven by the linear thermal

expansion of solid materials. Despite the good performance, the HP valves havenot yet been commercialized due to business reasons and the NovaSensor

valves are in the final phase of development. The performance of micro valves

compares favourably with macroscopic solenoid valves. In particular, Micro

valves typically operate faster and have a longer operational lifetime. However,

since micro valves are typically driven by thermal actuators their power

consumption is still relatively high (0.1-2.0 W). Care must be taken to preventthe valve temperature to exceed that tolerated by the fluid or gas media being

controlled.

Micro pumps:Several methods of micro actuation have been used to drive micro

pumps: electrostatic forces, magnetic forces, and piezoelectric. One example isa miniaturized gear pump that consists of LIGA micro gears that are

magnetically actuated It has been commercialized by MEMS tech Products,

LLC, of Vancouver, Washington.


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Another example is an electro statically driven micro pumpproduced by bonding multiple bulk micro machined silicon wafers together.

The bonding process creates a pumping cavity with a deformable membrane

and two one way check valves. The electrodes are fabricated inside a second

isolated cavity formed above the deformable pumping membrane so that they

are sealed away from the conductive solutions being pumped Although the

micro pump works well, high voltages (>100 V) are required for significant

pumping to occur. Electrostatic micro pumps with two one-way check valves.

When designing micro pumps for biomedical applications, attention must be

paid to the media being pumped. Some fluids, such as insulin, cannot tolerateaggressive pumping mechanisms without degrading.

BIOMEDICAL MICROSYSTEMS:


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The ability to miniaturize entire biomedical systems, such as DNA

analysis, chemical analysis, drug development, and neural prosthetics, has the

potential to reduce the cost of health-care management. For example, reducing

the cost and complexity of performing DNA screening and chemical analysis to

the point that tests can be performed rapidly on the desktop, would reduce theinfrastructure required for the test without compromising capability. This

would enable remote or small-scale clinics to offer fast high-quality tests.

Micro fluidic Systems:Chemical, pharmaceutical, and genetic analysis systems require the

precise handling of fluids (i.e., sampling, mixing, heating, cooling, reacting, and

Separating).Conventional fluidic analyses are typically performed with

relatively macroscopic fluidic systems (>25 L). Miniaturization and integration

of fluidic systems offers the following advantages: (1) smaller typical operating

fluid volume, (2) precise control of sample volumes, (3) ability to perform

massively parallel tests, (4) take advantage of the effect of scaling on fluidic,

electrical, and thermal behaviour, (5) possible reduction in system size, and (6)possible reduction in system cost. One important caveat with miniaturizing

fluidic analysis systems is the fact that reducing the sample size requires a

corresponding increase in sensor sensitivity. In addition, micro-scale fluid flow

is almost completely laminar (i.e., there is very little turbulence and thus mixing

can be problematic).

Micro Total Analysis Systems (TAS):The ability to electrically control fluid flow in micro machined

channels (i.e., pumping and valving) without any moving parts has enabled the

realization of complex micro total analysis systems. With multiple

independently controlled flow channels, complex sample preparation, mixing,and testing procedures can be established. The electrically controlled pumping


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and valving mechanism is either electro osmotic flow or electro phoretic flow.

Liquid chromatography (i.e., a method of separating liquids based on their

different mobility in a long flow channel) can be used to perform a precise

chemical analysis in micro fabricated flow channels. Sensors integrated at the

end of the flow channel will reveal a time-domain spectrum of the fluidcomposition. Micro machined electro phoretic devices have been used to

separate ions and DNA molecules from 70 to 1000 bases in under 2 minutes

much faster than conventional capillary electrophoresis systems. The detection

of each ion or molecule species can be accomplished with electrochemical

measurements, fluorescence, or optical absorption.

Microsystems for Genetic Analysis:The analysis of genetic material typically calls for first the

amplification of the DNA sample and then its detection. The amplification of a

DNA sample can be accomplished by polymerase chain reaction (PCR). The

PCR process begins by heating the DNA sample above the temperature at which

the two strands separate or melt (~90 to 95C). If the DNA polymeraseenzyme and the building blocks of DNA (i.e., nucleotide triphosphates) are

present during cooling, the DNA polymerase will then reconstruct each double

helix resulting in a doubling of the number of DNA stands. A major advantage

of miniaturizing PCR systems is the fact that the much lower thermal mass of

the reaction chamber allows for more rapid heating and cooling and thus a muchfaster process overall. Furthermore, it is even possible to integrate heaters and

temperature sensors into the same chip to allow for improved temperature

control.

Gene Chips:Separation by electrophoresis can be used to detect the size of a DNA

molecule, but another method is needed to determine its precise code. One

method exploits the highly selective hybridization process that allows DNA

fragments to bind only with their complimentary sequence. In order to test formany specific sets of DNA sequences (i.e., for genetic screening), a large

number of unique oligonucleotide probes need to be constructed and compared

to the amplified DNA.


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One novel method of constructing oligonucleotide probes employs the

same lithographic techniques used to construct MEMS. Specifically, a substrate

is coated with a compound that is protected by a photo chemically cleavable orphoto labile protecting group (e.g., nitro veratryloxy carbonyl). When this film

is exposed to a pattern of light, the illuminated regions will become unprotected

and can be conditioned to receive a specific nucleotide / photo labile protecting

group pair. By continuing the processes with a new mask pattern each time,

very large arrays of unique combinations of nucleotide can be rapidly formed.

The process is repeated until the desired oligo nucleotides are constructed. After

tagging the sample DNA with a fluorescent probe, it is then distributed over the

array of oligonucleotide probes. Subsequent optical inspection of the

distribution of fluorescence clearly indicates which oligo nucleotides in thearray match with a section of the sample DNA.


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Miniaturization of this detection system enabled massively parallel

screening (i.e., 40,000 different compounds can be tested on a single 1 cm chipwith 50 m oligonucleotide probe areas. Affymetrix, Inc has commercialized a

DNA detection scheme based on this technology.

CONCLUSIONS:Micromachining and MEMS technologies are powerful tools for

enabling the miniaturization of devices useful in biomedical engineering.

Although silicon micro machined pressure sensors presently possess the largest

share of the Bio MEMS market in terms of volume and sales, it is anticipated

that the market share of MEMS-enabled chemical sensing and micro fluidic

systems will grow tremendously. In addition, MEMS will continue to be applied

to bio medical engineering in new research activities that push our

understanding of cells, organs, the brain, the body, and the world around us.

REFERENCES:[1] Micromechanics and MEMS: Classic and Seminal Papers to 1990,

W. Trimmer (Ed.),IEEE Press, New York, NY, 1996, ISBN

[2] G. T. A. Kovacs, Micro machined Transducers Source book.WCB/McGraw-

Hill, 1998, ISBN.

[3] M. Madou, Fundamentals of Micro fabrication. Boca Raton, FL: CRC Press,

Inc., 1997, ISBN.[4] J. Bustillo, R. T. Howe, and R. S. Muller,Surface micromachining for micro electromechanical systems, Proceedings of

the IEEE, vol. 86, no. 8, August 1998, pp. 1552-1574.

bio medical applications of mems

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