BioMEMS Applications in Medicine

Dennis L. Polla University of Minnesota Department of Electrical and Computer Engineering Minneapolis, Minnesota USA 55455 Tele: 1-650-230-1571; e-mail: p.?, U Abstract: Biomedical microsystems (BioMEMS) integrate microscale sensors, actuators, microfluidics, micro-optics, and structural elements with computation, communications, 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 microinstrumentation), and therapeutic microsystems (health care management systems). Some representative examples based on work carried out at the University of Minnesota are presented including 1) MEMS in precision surgery ophthalmology, 2) MEMS in biomolecular recognition, and 3) MEMS in autonomous therapy management systems micropumps for drug delivery. Selected human clinical trials of the application of BioMEMS will be presented. 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 oxide/nitride 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 piezoelectric material, a smooth inchworm motion is created through 1.2 pm steps and 38 mm overall travel as shown in Fig. 1.

1 INTRODUCTION .
BioMEMS' represents a promising new direction in meeting 2lStcentury 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.

2001 INTERNATIONAL SYMPOSIUM ON MICROMECHATRONICS AND HUMAN SCIENCE 0-7803-7190-9/01/ $10.00 02001 IEEE.

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These include precision cutting, endoscopy, biopsy, and site-specific drug delivery.

3. DIAGNOSTIC MICROSYSTEMS
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 Fig. 1. Basic operation of a MEMS piezoelectric change in a physical parameter. We have stepper motor. developed a resonant inertial mass change detector to perform such functions as analysis Five prototype hand-held micromotors of common diseases, identification of genetic (example shown in Fig. 2) have been predispositions,and drug discovery. constructed and tested. Motor speeds were found to depend on the applied frequency and We have developed a silicon micromachining technology to realize biomolecule-coated chosen operating conditions. 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 Aflf,, = S, Am

(1)

Fig. 2. Optical micrograph of a handheld surgical where S, is a proportionality constant tool using the piezoelectric stepper motor. dependent on beam dimensions, damping effects, etc. The tested micromotors had 1.2mmls advancement speeds against 3 N attached Extremely high mass-change detection loads. The electrostatic clamp generates an approaching lo-'* gm has been demonstrated attraction force of 2.0 N using a clamp with an with this device. An optical micrograph of a area of 3.75 cm2 and 150 V across the molecular recognition biosensor is shown in dielectric medium between the silicon wafers. Fig. 3. 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 Fig. 3. SEM of a piezoelectric molecular re cognition cantilever. attachment tools at the end of the micromotor.

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

->+'lCtene@

^^

GaiGx~w$i@ i>e@.BC$Pt

Fig. 6. Micromachined silicon-glass needles with tip 35 pm tip dia.

5. CONCLUSIONS

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

4. THERAPEUTIC MICROSYSTEMS
Therapeutic microsystems offer the potential of autonomous care management and precision delivery of medications. Some key MEMS technologies currently being incorporated into such systems include micropumps, microvalves, and microneedles. Two representative examples of devices fabricated at the University of Minnesota are shown in Figs. 5 and 6. While there are many systems integration challenges, early component development has shown an encouraging future.

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 unprecendented amounts of new data including the presence or absence of disease and the identification of biomarkers that predict the development of disease in onne's lifetime. Therapeutic microsystems such as autonomous therapies managment 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, biocompatibility, and government approval issues intersect the advancement of the technology. These challenges are not insurromountable and Fig. 5. Piezoelectric micropumps for precision will most likely be characteristic of the microfluidic dispensing. Each same development efforts required in other diaphragm measured 300 i m-dia. medical devices and pharmaceuticals

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 d mineering, Vol. 2,2000, pp. 552-572.
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