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MEMS Technology for Biomedical Applications

Dennis L. Polla University of Minnesota

Deparmtent of Electrical and Computer Engineering Minneapolis, Minnesota 55455, USA

Tele: 1-650-230-1571; e-mail: polla@ece.umn.edu

Abstract

MEMS technology is enabling a wide variety of biomedical systems. This technology is now integrating microscale sensors, actuators, microfluidics, micro-optics, and structural elements with computation, com-munications, and controls for application to medicine for the improvement of human health. Derived from the microfabrication technology used to make integrated circuits, BioMEMS is expected to revolutionize the way medicine is practiced and delivered. This paper presents an introductory overview of three exciting new opportunity areas of BioMEMS in medicine. These are surgical microsystems (intelligent micro-invasive surgical tools), diagnostic microsystems (biochips and related micro-instrumentation), and therapeutic micro-systems (health care management systems). Some representative examples based on work carried out at the University of Minnesota (USA) are presented including 1) MEMS in precision surgery - ophthalmology, 2) MEMS in biomolecular recognition, and 3) MEMS in autonomous therapy management systems - micro-pumps for drug delivery. Selected human clinical trials of the application of BioMEMS will be presented.

1. Introduction

BioMEMS'.' represents a promising new direction in meeting 21" century health care challenges.

Opportunities in miniaturization allow for new medical procedures to be performed as well as existing procedures to be carried out less invasively. The ability to apply batch fabrication methods to the manufacture of BioMEMS might also enable greater accessibility to medical procedures through a lower overall cost of health care delivery. This paper is intended to present some representative examples of promising BioMEMS. It is not intended to be a survey of the literature our listing of the many exciting BioMEMS approaches being pursued around the world.

2. Surgical Microsystems

A piezoelectric micromotor has been constructed and tested for precision surgical applications. The motor which is designed to fit in a hand-held stainless steel cylinder (1.2 x 15 cm) uses two silicon wafers and a piezoelectric bar. A simple operating principle for the micromotor uses an electrostatic clamp formed across an oxidehitride dielectric between two silicon wafers to immobilize the micromotor while piezoelectric actuation generates both a force and displacement. Movement is generated by using the inertial properties of an attached mass coupled with fast and slow expansions / contractions of the piezoelectric (PZT) material. The fast transitions use the inertia of the mass to ,move the clamp, while the slow transitions move the mass while keeping the clamp stationary. By applying the proper three-steps sequential actuation (typical frequency: 400-800 Hz) to the two electrostatic clamps and

0-7803-6520-8/0~/510.00 GI 2001 IEEE.

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piezoelectric material, a smooth inchworm motion is created through 1.2 pn steps and 38 mm overall travel as shown in Fig. 1.

Fig. 1 . Basic operation of a MEMS piezoelectric stepper motor.

Five prototype hand-held micromotors (example shown in Fig. 2) have been constructed and tested. Motor speeds were found to depend on the applied frequency and chosen operating conditions.

Fig. 2. Optical micrograph of a handheld surgical tool using the piezoelectric stepper motor.

The tested micromotors had 1 . 2 d s advancement speeds against 3 N attached loads. The electrostatic clamp generates an attraction force of 2.0 N using a clamp with an area of 3.75 cm2 and 150 V across the dielectric medium between the silicon wafers. Maximum step sizes for the PZT used are approximately 10 pm, and steps less than 100 nm can be obtained with sufficiently low PZT voltages.

The micromotors constructed have been designed for ophthalmic applications, namely the insertion of a replacement lens into the eye immediately following cataract removal. The piezoelectric stepper motor developed however has a much broader range of applications through interchangeability of attachment tools at the end of the micromotor.

3. Diagnostic Microsystems

Molecular Recognition Biosensors

Biomolecular recognition micro-sensors can potentially provide a cost-effective approach to rapidly and cost-effectively diagnose the human condition. These devices usually contain selective molecule surfaces onto which an appropriate conjugate molecule selectively binds producing a measurable change in a physical parameter. We have developed a resonant inertial mass change detector to perform such functions as analysis of common diseases, identification of genetic predispositions, and drug discovery.

We have developed a silicon micromachining technology to realize biomolecular-coated microcantilever beams with piezoelectric thin films. The piezoelectric material is used to generate a resonant oscillation at frequency f,,. Incremental mass loading Am is detected by specific conjugate biomolecule binding to confirm the presence of a biochemical reaction. This result is read out in the form of a downward shift in resonant frequency Af according to the relation

where S, is a proportionality constant dependent on beam dimensions, damping effects, etc.

Extremely high mass-change detection approaching lo- gm has been demonstrated with this device. An optical micrograph of a molecular recognition biosensor is

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shown in Fig. 3.

Fig. 3. SEM of a piezoelectric molecular recognition cantilever.

A representative mass change spectrum for biotin-avidin binding is shown in Fig. 4.

I 64 1 i~ l la i I r n 3 w x 1mm lzgla wm

i InlUYnCMH: 3

- ;snCwm: -- GafW&q Ga@fJL1F)

Fig. 4. Resonant frequency shift on recognition microcantilever sequential binding of avidin and BCIP on biotin surface.

Miniature Mass Spectrometers

A miniature mass spectrometer has beendesigned and fabricated for the detection of gas molecules of low molecular weight? The device is based on a compact double-focusing mechanism that deflects ions in a 90" cylindrical crossed electric and magnetic field sector analyzer with a radius of 2.0 cm. MEMS approaches in realizing the key components of miniature mass spectrometers are plentiful. Our work has been directed toward MEMS realization of the ionizer and

mass separator. We used commercially available small vacuum pumps and ion detectors in our initial work. An optical photograph of the core device is shown in Fig. 5. A representative spectrum obtained for air is shown in Fig. 6.

Fig.5. Optical photograph of miniature field Sector mass Spectrometer.

Fig. 6. Residual gas analysis of air.

4. Therapeutic Microsystems

Therapeutic microsystems offer the potential of autonomous care management and precision delivery of medications. Some key MEMS technologies currentlybeing incorporated into such systems include micropumps, microvalves, and microneedles. lbo representative examples of devices fabricated at the University of Minnesota are shown in Figs. 7 and 8. While there are many systems integration challenges, early component development has shown an encouraging

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future.

Fig. 7. piezoelectric micropumps for precision microfluidic dispensing. Each diaphragm measured 300 pm-dia.

fig. 8. Micromachined silicon-glass needles with tip 35 pm tip dia.

5. conclusions

BioMEMS represents an exciting and growing field with opportunities of improving the human condition and reducing the cost of health care delivery. Surgical microsystems offer potential advantages of allowing intelligent, precision surgery with a shorter recovery time for the patient. Diagnostic microsystems potentially will enable the collection and processing of unprecedented amounts of new data including the presence or absence of disease and the identification of biomarkers that predict the development of disease in ones lifetime.

Therapeutic microsystems such as autonomous therapies

management systems will potentially allow people currently on complicated therapies that involve continuous human intervention to lead normal lives.

Many challenges exist for BioMEMS including long product development times particularly when safety, biwompatibility, and government approval issues intersect the advancement of the technology. These challenges are not insurromountable and will most likely be characteristic of the same development efforts required in other medical devices and pharmaceuticals.

Acknowledgements

The author would like to thank the many colleagues (Profs. W. Robbins, A. Erdman, S. Mantell, P. Krulevitch, A. Wang, and L. Francis) and students (Drs. J. Diaz, D. Markus, T. Tamagawa, L. Li, H.T. Brickner, J. Kim, and J. Yi) at the University of Minnesota who have contributed to t h i s work

References

Contributions contained in this paper have recently been reported at-2001 International Symposium on Micromechatronics and Human Science, D.L. Polla, BioMEMS Applications in Medicine, Nagoya, Japan, September 10,2001 (invited). D. L. Polla, A. G. Erdman, W. P. Robbins, D. T. Markus, J. Diaz-Diaz, R. Rizq, Y. Nam, H. T. Brickner, P. Krulevitch, and A. Wang, Microdevices in Medicine, Annual Review of Biomedical Engineering, Vol. 2,2000, pp. 552-572. J. A. Diaz, W. R. Gentry, C. F. Giese, and D. L. Polla, A Miniature Superimposed ExB Sector Field Mass Spectrometer, The 48 ASMS Conference on Mass Spectrometry and Allied Topics, Long Beach, CA June 2000 (invited).