Lecture 16: Bio-MEMS - engr.uvic.camech466/MECH466-Lecture-16.pdf · 3 What are Bio-MEMS? ‘Bio-MEMS’ is a term used to describe the use of MEMS devices that interact with biological

1

MECH 466Microelectromechanical Systems

University of VictoriaDept. of Mechanical Engineering

Lecture 16:Bio-MEMS

© N. Dechev, University of Victoria

2

Introduction to Bio-MEMS

Biocompatible Materials

Case Studies

Overview


3

What are Bio-MEMS?

‘Bio-MEMS’ is a term used to describe the use of MEMS devices that interact with biological phenomena.

The use of Bio-MEMS can take place in two ways:


(1): in vivo (within a living body) (2): in vitro (in a glass dish, tube, etc...)

X-ray of abdomen with in vivo sensors[M. J. Serpe and X. Zhang]

Myoglobin-Based Optical Biosensor[Todd A. Wells, Univ. of Denver, Dept. of Chem. and Biochem.]

4

What are Bio-MEMS?

The subject of “Bio-MEMS” can be roughly split into two main areas, corresponding to the ‘sensors and actuators’ theme of this course:

Bio-sensors-in vivo measurement of:

- blood physics and chemistry- muscle and nerve electrical signals- other body physiology- various other implant applications.

- in vitro measurement of bio-fluids:- blood chemistry- proteins, DNA- cell detection and analysis

Bio-actuators-cell manipulation, cell sorting-in vivo electrical stimulation-in vivo drug delivery


5

Some biological systems or processes are ‘micro-scaled’ in nature. Hence, MEMS technology may be able to better measure or sense these processes.

Bio-MEMS sensors can operate in-vitro, when biological samples are removed from the environment or a living system, and placed within a device employing the MEMS sensor.

Bio-MEMS sensors could also be implanted into a living body (in-vivo), to monitor biological processes or other functions.


MEMS Bio-Sensors

6© N. Dechev, University of Victoria

MEMS Bio-Sensors Examples:

(a) in vivo blood pressure sensor

Omron piezoresistor-based biomedical pressure sensor[http://nextgenlog.blogspot.com/2009_11_01_archive.html]

(b) in vivo test for Flu, Cancer, and Toxins

IBM implementation of ‘lab on a chip’ for high-speed analysis[http://nextgenlog.blogspot.com/2009_11_01_archive.html]

7

Generally a MEMS mechanical structure (cantilever beam, membrane, diffraction grating, etc...) that is coated with a substance (protein, anti-body, etc...) that causes ‘highly specific’ types of biological cells (bacterial) or chemicals, to stick to it.

In the simplest case, a “coated cantilever beam” may be used, for detection of biochemical species including anthrax, nerve gases, NOx, etc...


Cantilever Based Cell/Particle Detector[Image from EPFL-LAMI]

MEMS Bio-Sensors Examples:Chemical & Biological Agent Detection System:

Microcantilever MEMS sensor array[ E.S. Kolesar][http://www.engr.tcu.edu/newsite/faculty_ekolesar.asp]

8

The amount of ‘force’ produced by a MEMS actuator is extremely small. However, if we design a MEMS to use this force in a clever way, we can actuate MEMS devices to perform useful biomedical functions.

Bio-MEMS actuators can operate in-vitro, when biological samples are removed from a living system and placed within a device such as a lab-on-a-chip. Perhaps they can be used to pump fluids, heat fluids, apply electric or magnetic fields, etc...

Bio-MEMS actuators can also be implanted into a living body (in-vivo), to perform special functions.


MEMS Bio-Actuators


MEMS Bio-Actuators Examples:

(a) in vivo drug delivery with MEMS

Drug reservoirs made with bulk etching of Si Crystal. Note: Cover caps not shown[http://www.technologyreview.com/business/19784/]

(b) in vivo drug delivery with electrothermally activated microchips

Detailed schematic of single reservoir showing cap and ‘fused seal’that melts open when current is applied at electrodes. [M. Maloney, et al., “Electrothermally activated microchips for implantable drug delivery and biosensing,” Journal of Controlled Release, Vol. 109, 2005, pp.244–255]

MembraneCurrentflow

ReservoirSealing layer or additional substrate

Trace

Dielectric

Substrate


MEMS Bio-Actuators Examples:

(b) in vivo drug delivery with electrothermally activated microchips

[M. Maloney, et al., “Electrothermally activated microchips for implantable drug delivery and biosensing,” Journal of Controlled Release, Vol. 109, 2005, pp.244–255]

(a) Nominal current: 2.2 A

Opening size: 0%

(b) Nominal current: 2.6 A

Opening size: 8%

(c) Nominal current: 2.9 A

Opening size: 42%

(d) Nominal current: 3.5 A

Opening size: 84%

(e) Nominal current: 4.9 A

+


MEMS Bio-Actuators Examples:Transdermal Drug Delivery:

SEM image of several microneedles. The length of the needles is 400 µm, and the needle pitch is 500 µm. Eachmicroneedle chip contains 25 needles.[N. Roxhed, T.C. Gasser, P. Griss, G.A. Holzapfel, and G. Stemme, “Penetration-Enhanced Ultrasharp Microneedles and Prediction on Skin Interaction for Efficient Transdermal Drug Delivery”, Journal of Microelectromechanical Systems, Vol. 16, No. 6, Dec 2007]

Process flow of the fabrication of side-opened hollow microneedles.

12

‘biocompatibility’ generally means to have no toxic or adverse effect on a living organism, or to a subset of that organism, such as cells, tissue, etc... Something that is biocompatible will not trigger an immune response (leading to rejection) if it is placed in or on a living organism.

The term‘biocompatible’ may refer to a specific material, or more generally, to an entire device.

Since the objective of Bio-MEMS devices is function within the body (in-vivo), or to analyze living tissue/cells (in-vitro), it is important to ensure that any portion of the device that is in contact with the body/cells is ‘biocompatible’.


Biocompatibility

13

‘Rejection’ occurs when the material/device placed within the body triggers an immune response. The rejection phenomena can lead to various reactions, some being mild, and others being severe.

Some examples of rejection include:- Expulsion from the body (i.e. silicon, glass)- Encapsulation of the material in anti-bodies- Inflammation of the surrounding tissue- Toxicity to the surrounding tissue, leading to tissue death- Leaching of the material into blood stream, spreading

toxic effects throughout the body.


Rejection

14

Typical materials that are considered as ‘biocompatible’, and have been used in micro-fabrication of MEMS devices include:

- PMMA (acrylic)- Paralyne- Many polymers (each polymer is unique)- Gold- Titanium (only recently)- Some ceramics: Silicon nitride and silicon carbide

Other common MEMS materials are not bio-compatible.- Glass is appropriate for in-vitro, but not in-vivo.- Silicon requires surface treatment for in-vitro, and is also

not compatible for in-vivo applications.


Biocompatible MEMS materials

In the field of cell biology, it is sometimes useful to be able to isolate and immobilize individual cells for study.

One manner in which to capture free floating cells, and array them into an ordered pattern on a surface, is through the use of magnetic MEMS.

With the exception of blood cells, most biological cells are non-magnetic, and hence the first step is to magnetically ‘label’ the cells.

15

Magnetic Single Cell Micro Array (MSCMA)

Desired Cell

Magnet Disc

‘Tetrameric antibody complexes’ are designed to (a) attach to target cell at one end and (b) attach to magnetic material at other end.


16

Desired Cell



17

Desired Cell


Desired Cell

Desired Cell

Desired Cell

Desired Cell

Desired Cell

Desired Cell

Desired Cell


18


By using an external magnetic field, we can create geometrical patterns that will ‘focus’ the magnetic field at specific points.

Illustration of (a) MSCSA Device top view,(b) close-up 3D view with permalloy (grey) and gold (orange). [William Liu]

Cell capture results with (a) actual test, (b) control test (no external field applied). [William Liu]


19

Desired Cell

In-Vitro Biological MEMS Sensors


20

Case Study: Implantable Bio-Sensorsfor Advanced Prosthesis Control

Existing State-of-the-art:

Conventional prosthesis technology is often limited to 1-2 degrees of freedom (DOF, or independent control channels) of motion.

The functionality of such devices is limited to 1-DOF open/close grips, or 1-DOF wrist rotations, such as shown below with Otto-bock, VASI, and others...


Otto-Bock System Electric Hand, size 7,[www.ottobock.com]

VASI Electric Hands, size 0 - 11 years[http://www.liberatingtech.com/products/VASI_Electric_Hands.asp]

21

This is a consequence of conventional techniques to measure signals from the body (EMG, i.e. electromyographic signals) and translate them into commands understood by the machine (i.e. prosthesis).

Currently, one-or-two DOF control using ‘Myo-electric’ sensors, and various control schemes, is used to open and close most prosthetic devices.

Two channel control is possible for some users, but three or more channel control is very difficult to achieve.

Otto-Bock Hand withBloorview Macmillan Fiberglass Socket and Myo-Electric Sensors

Conventional Prosthesis Control


- Otto-Bock Hand (above)- TBM Hand [N. Dechev] (below)

22

Experimental Hand ProsthesisA number of other multi-fingered hands (robotic or prosthetic) using various strategies for adaptive grasp exist, to name just a few:

- The Southampton Hand [Kyberd, Chappell, et al]

- Montreal Hand [Lozac’h, et al]

- Belgrade/USC Hand [Bekey, et al]

- Utah/MIT Hand [Jacobsen, et al]

- Shadow Hand* [www.shadowrobot.com]

- i-LIMB Pulse* [www.touchbionics.com/Pulse]

- and many more...

Southampton Remedi-Hand [P. Chappell]

Shadow Hand*[www.shadowrobot.com]

i-LIMB Pulse*[www.touchbionics.com/Pulse]


* These hands feature many mechanical DOF, but are still controlled by only one (or two) channel user input (i.e. human being input).

23

The Prosthesis Control Problem

We have all see movies such as ‘Star Wars’, ‘Terminator’, etc... all featuring advanced robotic hands. We certainly have the tools and materials to machine/fabricate such devices today!

THE QUESTION IS: Why are these multi-fingered hands not widely used as prosthesis? The need/desire for such devices is very high.

ANSWER:

Consider a hypothetical prosthesis that is multi-fingered, flexible fingered, with a rotatable & flexing thumb, and a moveable wrist. Such a device would have 10+ (or more) mechanical DOF.

To simultaneously move/coordinate these 10+ DOF, a human being needs to provide 10+ independent channels of user input!

We still lack the technology to ‘reliably & simultaneously’ collect & process 10 channels of user input, and further to use this input to control these types of advanced prosthesis by a human being. Current commercially available systems can handle at most 2-3 channels (as described here).


24

MEMS-based Sensor Implants for Prosthesis Control

Multiple implanted sensors may be able to detect sufficient multi-channel input from biosignals within the body.

Inspiration from Microchip implants for Pets.

Challenges: Size, Power, Communication, Bio-compatibility.

Territory for 3D MEMS/CMOS Hybrid Technology.

Multiple implanted actuators may be able to provide multi-channel output (via stimulation) to provide feedback to the body, from the device.


25

HandProsthesis

WristProsthesis

ImplantSensors

WearableDriver/Receiver


Proposal: MEMS Sensor for Prosthesis Control

26

Chip Substrate

CMOSMicro-Coil(Power)

Micro-Coil(Transmitter)

Micro-machinedTi Electrodes

EncapsulationMaterial

Anticipated Size: 2 x 0.4 x 0.4 mm

Proposal: MEMS Sensor for Prosthesis Control


27

Homework

The current proposals for Bio-MEMS applications are numerous.

For example:

Retinal implants

In-vivo Blood Glucose measurement

Cochlear implants

Stents

FOR HOMEWORK: Find a recent R&D area for Bio-MEMS, and write a 2 page summary of the technology. Beyond the summary, comment on whether you think the technology is feasible, given what you have learned about MEMS thus far.


Documents

Lecture 16: Bio-MEMS - engr.uvic.camech466/MECH466-Lecture-16.pdf · 3 What are Bio-MEMS? ‘Bio-MEMS’ is a term used to describe the use of MEMS devices that interact with biological