lecture 9 biomedical microtechnology and nanotechnology · the plates of a micro sized capacitor...

chnolo

Nanote

chnolo

Microfabricationand Nanofabrication

applied to Biomedical Instrumentation

Why Micro/Nano?

SCALING OF PARAMETERS

The values of various parameters depends on the dimensions of the system

and this proves to be helpful in a number of cases.

antile

bendin

echanic

al Para

Force F

Deflection d

Density of Material = 3.5 x 103kg/m

Young’s Modulus = 1012N/m

Material properties such as Young’s modulus remain approximately the

same in the micro and macro versions.

However, they are relatively more different in case of nanodimensions

because nanodimensions come closer to molecular level.

Why Micro/Nano?

Mass = Density x Volume = Constant x S

Consider that the dimensions of the cantilever are reduced 10000times, i.e

the length, breadth and thickness change from 100 cm, 10cm and 1cm to

100microns, 10 microns and 1 micron respectively.

If S represents any dimension in general then,

Therefore mass goes down (104)3or is reduced 1012times as the original beam

Total strength scales with its cross-sectional area. Hence, total strength scales

2. Hence, total strength to mass ratio scales as S

As a result, the micro cantilever is 104times stronger than the macro model.

Why Micro/Nano?

Deflection

Moment of Inertia

Young’s Modulus

thickness

breadthlength

Force will vary with cross-sectional area if the stress is to be kept constant

Therefore, deflection is proportional to S

1. Therefore, the same stress is

generated in the two models if the deflection in the microcantileveris 10-4

times the deflection in the macro model, thus maintaining the bending shape.

A much smaller force can be sensed (10-8times) with the micro cantilever.

quency

Frequency scales as the square root of the ratio of the stiffness and

mass. Thus, frequency scales as S

-1. Hence, micro and nano

applications can be high frequency applications.

Huang e

t al h

echanic

alsilic

resonato

r ultra

quency

applications.

Resonant fr

equencie

rence :

equency%

apacitor(E

ical P

Voltage

Voltage = E x gap

Thus, voltage will scale as the gap between the plates.Therefore a

much smaller voltage will be required in the micro case to produce

the same effect.

If the same electric field E = 108V/m needs to be mainitainedbetween

the plates of a micro sized capacitor and a macro sized capacitor, then

Electrostatic force = Area x (electrostatic field)2

Thus, electrostatic force scales as S

2if electrostatic field is maintained same.

However, if voltage is to be maintained same, electrostatic force would be

independent of scaling.However, its effect in the micro case would be more

pronounced because relatively, inertial forces are very low.

Electromagnetic force scales as S

4 if magnetic field is to be constant and thus,

the world of memsrelies on electrostatic motors as opposed to electromagnetic

motors .

Capacitance

Capacitance scales as S

An electrostatic micromotor

An electrostatic comb drive actuator

Advantages of Micro/NanoFluidics

for Biomedical Applications

r hand-h

tion and poin

t-of-care

sting is m

•Pro

f expensiv

reagents

duction

posable

icsyste

•Pre

ol of sam

eagents

h leads to h

igher sensitiv

igh-thro

ughput

possib

pling tim

es thro

llel pro

cessin

-situ p

roduction o

f unsta

pounds for

al assays

atio o

f surf

rea to v

me is h

nd thus, th

effective in c

ical sensors

Disadvantages of Micro/Nano

Fluidics for Biomedical Applications

lock e

olled b

ither prim

ressure

r by u

rent prim

such a

thanol or carb

e filte

ring o

f solu

tions b

•Surf

ace tensio

lays funny.

roscale

modeling n

eeds to b

echanic

s is n

rly intu

ever, s

ace tensio

n forc

ited a

ith the m

ment is

not easy.

Micro/Nanoapplied to BME

Taken from : http://mems.colorado.edu/c1.res.ppt/ppt/g.tutorial/ppt.htm

Taken from : www.heartcenteronline.com

Balloon Angioplasty

StentProcedure

cedure

loon A

Micromachinedsilicon neural probe arrays

Taken from

http://www.ee.ucla.edu/~jjudy/publications/conference/msc_2000_judy.pdf

Michigan Probe

Drug Delivery Probes

An implantable blood

pressure sensor developed

by CardioMEMS

Surgical microgripperactuated by SMA

Taken from

Micro/Nano

Fabrication Techniques

Generalized Microfabrication

Photolithography

r: to remove particles on the surface as well as any

traces of organic, ionic, and metallic impurities

Dehydra

tion b

ake: to drive off the absorbed water on the surface

to promote the adhesion of PR

Coating :

a) Coat wafer with adhesion promoting film

(e.g., HMDS) (optional)

b) Coat with photoresist

bake: to drive off excess solvent and to promote adhesion

Exposure

Post exposure

bake(optional): to suppress standing wave-effect

Develo

bake: to harden the PR and improve adhesion to the

substrate

Photolithography

Taken from :http://www2.ece.jhu.edu/faculty/andreou/495/2003/LectureNotes/Handout3a_PhotolithographyI.pdf

Thermal Oxidation of Silicon is done in a furnace in wet or dry conditions

g in M

-Make P++ etch stop

-Change restivityof the film

(e.g. make piezoresistor,connectingwire)

Dopants: N type (Phosphorous, Arsenic), P type (Boron)

1.Diffusion

Dopantsare diffused thermally into the

substrate in furnace at 950 –1280 0C.

It is governed by Fick’sLaws of Diffusion.

Dopantions bombarded into targeting

substrate by high energy.

Ion implantation are able to place any ion at

any depth in sample.

2. Ion Implantation

Physic

Depositio

vapora

Thermal Evaporator

Deposition is achieved by evaporation

or sublim

ation of heated metal onto

substrate.

This can be done either by resistance

heating or by e-beam bombardment.

Additive Processes

Physic

Depositio

2. Sputtering

Sputtering is achieved by accelerated

inert ion (Ar+) by DC or RF drive in

plasma through potential gradient to

bombard metallic target.

Then the targeting material is

sputtered away and deposited onto

substrate placed on anode.

Additive Processes

Physic

Depositio

Additive Processes

ical V

apor D

epositio

deposited

Polysilicon, silicon nitride (Si3N4), silicon oxide (SiOx), silicon carbide (SiC) etc.

does C

EGaseous reactants are introduced into chamber at elevated temperatures.

EReactant reacts and deposits onto substrate

Types o

LPCVD (Low Pressure CVD), PECVD (Plasma Enhanced CVD)

Salient Featu

ECVD results depend on pressure, gas, and temperature

ECan be diffusion or reaction limited

EVaries from film

composition, crystallization, deposition rate and electrical and

mechanical properties

Subtractive Processes

Dry Etching

ical Etc

HF is a powerful etchantand hence, highly dangerous.

2XeF2+Si→2Xe+SiF4

EIsotropic etching (typically 1-3µm/min)

EDoes not attack aluminum, silicon dioxide, and silicon nitride

Reaction M

echanis

Produce reactive species in gas-phase Reactive species diffuse to the solid

Adsorption, and diffuse over the surface Reaction Desorption

Diffusion

Dry Etching

eactive Ion E

A very high-aspect-ratio silicon etch method

(usually > 30:1)

rocess

EEtch rate is 1.5 –4 µm/min

ESF6 to etch silicon

EApprox. 10nm flourcarbonpolymer (similar

is plasma deposited using C

EEnergetic ions (SF6+) remove protective

polymer at the bottom trench

DRIE Etched Pillars

Wet Etching

Isotropic etchantsetch in all directions

at nearly the same rate.

Commonly use chemical for Silicon is

HNA (HF/HNO3/Acetic Acid)

This results in a finite amount of

undercutting

Wet Etc

active P

rocesses

Wet Etching

Anisotropic etchantsetch much faster

in one direction than in another.

Etchantsare generally Alkali

Hydroxides (KOH, NaOH, CeOH, ..)

ESlower etch rate on (111) planes

EHigher etch rate on (100) and (110)

planes (400 times more faster than

the (111) plane)

ETypical concentration of KOH

is around 40 wt%

Reaction:

Silicon (s) + Water + Hydroxide Ions →

Silicates + Hydrogen

Wet Etc

Metal Patterning

Surface Micromachining

Example

An insulin pump fabricated by classic MEMS technology

(Surface Micromachining)

1. Pumping membrane

2. Pumping chamber

3. Inlet

4. Outlet

5. Large mesa

6. Upper glass plate

7. Bottom glass plate

8. patterned thin layer (for improved fluidics)

MEMS Packaging

Fabrication of

MicrofluidicChannels

Materials

•Silicon / Sicompounds

-Classical MEMS approach

-Etching involved

•Polymers / Plastics

-Newer methods

-primary die yet needed

-easy fabrication of subsequent

components

Etching Methods

Step 1 : Etching of Si

-Isotropic / Anisotropic

-HNA for isotropic

-KOH/EDP/TMAH for

anisotropic

-RIE can also be used

for high aspect ratios

Etching Methods

Step 2 : Closure of channel

a)Bonding another

substrate

b)LPCVD coating

c)Ground Plate Supported

Insulating Channels

Etching Methods

Step 2 : Closure

d) Closing Holes in the

mask material

-channel is defined

by a sequence of

holes.

-channel formed by

underetching

Etching Methods

Step 2 : Closure

e) Burying channels

beneath surface

-Trench made using

-KOH etching to form

microchannels

-Oxide fills trench

A Comparative study

Using Polymers/Plastics

•Imprinting and Hot Embossing

•Injection Molding

•Laser Photoablation

•Soft Lithography

•X ray Lithography (LIGA)

Imprinting/Embossing

•Stamp made in Sior

•Stamp pressed on

Plastic to form

microfluidic channels

•Many common

plastics successfully

imprinted

Soft Lithography

•Elastomericpolymer

cast in a Sistamp and

•Polymer is peeled off

•Channel architecture

thus transferred to the

polymer

•PDMS technology is

becoming popular

Laser Photoablation

•High aspect ratio

channels achievable

•Laser pulses in the

UV region used

•Sealing by thermal

lamination with a

PET/PE film

at 1250C

•Depth controllable

References

http://www.kuos.org/archives/MEMS%20Short%20Course.p

http://mems.colorado.edu/c1.res.ppt/ppt/g.tutorial/ppt.htm

http://mems.cwru.edu/shortcourse/

http://www2.ece.jhu.edu/faculty/andreou/495/2003/LectureNotes/Handout3a_Ph

otolithographyI.pdf

http://www.memsnet.org

chnolo

Nanote

chnolo

Microfabricationand Nanofabrication

applied to Biomedical Instrumentation

Why Micro/Nano?

The values of various parameters depends on the dimensions of the system

and this proves to be helpful in a number of cases.

antile

bendin

echanic

al Para

Force F

Deflection d

Density of Material = 3.5 x 103kg/m

Young’s Modulus = 1012N/m

Material properties such as Young’s modulus remain approximately the

same in the micro and macro versions.

However, they are relatively more different in case of nanodimensions

because nanodimensions come closer to molecular level.

Why Micro/Nano?

Mass = Density x Volume = Constant x S

Consider that the dimensions of the cantilever are reduced 10000times, i.e

the length, breadth and thickness change from 100 cm, 10cm and 1cm to

100microns, 10 microns and 1 micron respectively.

If S represents any dimension in general then,

Therefore mass goes down (104)3or is reduced 1012times as the original beam

Total strength scales with its cross-sectional area. Hence, total strength scales

2. Hence, total strength to mass ratio scales as S

As a result, the micro cantilever is 104times stronger than the macro model.

Why Micro/Nano?

Deflection

Moment of Inertia

Young’s Modulus

thickness

breadthlength

Force will vary with cross-sectional area if the stress is to be kept constant

Therefore, deflection is proportional to S

1. Therefore, the same stress is

generated in the two models if the deflection in the microcantileveris 10-4

times the deflection in the macro model, thus maintaining the bending shape.

A much smaller force can be sensed (10-8times) with the micro cantilever.

quency

Frequency scales as the square root of the ratio of the stiffness and

mass. Thus, frequency scales as S

-1. Hence, micro and nano

applications can be high frequency applications.

Huang e

t al h

echanic

alsilic

resonato

r ultra

quency

applications.

Resonant fr

equencie

rence :

equency%

apacitor(E

ical P

Voltage

Voltage = E x gap

Thus, voltage will scale as the gap between the plates.Therefore a

much smaller voltage will be required in the micro case to produce

the same effect.

If the same electric field E = 108V/m needs to be mainitainedbetween

the plates of a micro sized capacitor and a macro sized capacitor, then

Electrostatic force = Area x (electrostatic field)2

Thus, electrostatic force scales as S

2if electrostatic field is maintained same.

However, if voltage is to be maintained same, electrostatic force would be

independent of scaling.However, its effect in the micro case would be more

pronounced because relatively, inertial forces are very low.

Electromagnetic force scales as S

4 if magnetic field is to be constant and thus,

the world of memsrelies on electrostatic motors as opposed to electromagnetic

motors .

Capacitance

Capacitance scales as S

An electrostatic micromotor

An electrostatic comb drive actuator

Advantages of Micro/NanoFluidics

for Biomedical Applications

r hand-h

tion and poin

t-of-care

sting is m

•Pro

f expensiv

reagents

duction

posable

icsyste

•Pre

ol of sam

eagents

h leads to h

igher sensitiv

igh-thro

ughput

possib

pling tim

es thro

llel pro

cessin

-situ p

roduction o

f unsta

pounds for

al assays

atio o

f surf

rea to v

me is h

nd thus, th

effective in c

ical sensors

Disadvantages of Micro/Nano

Fluidics for Biomedical Applications

lock e

olled b

ither prim

ressure

r by u

rent prim

such a

thanol or carb

e filte

ring o

f solu

tions b

•Surf

ace tensio

lays funny.

roscale

modeling n

eeds to b

echanic

s is n

rly intu

ever, s

ace tensio

n forc

ited a

ith the m

ment is

not easy.

Taken from : www.heartcenteronline.com

Balloon Angioplasty

StentProcedure

cedure

loon A

Micromachinedsilicon neural probe arrays

Taken from

Michigan Probe

Drug Delivery Probes

An implantable blood

pressure sensor developed

by CardioMEMS

Surgical microgripperactuated by SMA

Taken from

Micro/Nano

Fabrication Techniques

Generalized Microfabrication

Photolithography

r: to remove particles on the surface as well as any

traces of organic, ionic, and metallic impurities

Dehydra

tion b

ake: to drive off the absorbed water on the surface

to promote the adhesion of PR

Coating :

a) Coat wafer with adhesion promoting film

(e.g., HMDS) (optional)

b) Coat with photoresist

bake: to drive off excess solvent and to promote adhesion

Exposure

Post exposure

bake(optional): to suppress standing wave-effect

Develo

bake: to harden the PR and improve adhesion to the

substrate

Photolithography

Taken from :http://www2.ece.jhu.edu/faculty/andreou/495/2003/LectureNotes/Handout3a_PhotolithographyI.pdf

Thermal Oxidation of Silicon is done in a furnace in wet or dry conditions

g in M

-Make P++ etch stop

-Change restivityof the film

(e.g. make piezoresistor,connectingwire)

Dopants: N type (Phosphorous, Arsenic), P type (Boron)

1.Diffusion

Dopantsare diffused thermally into the

substrate in furnace at 950 –1280 0C.

It is governed by Fick’sLaws of Diffusion.

Dopantions bombarded into targeting

substrate by high energy.

Ion implantation are able to place any ion at

any depth in sample.

2. Ion Implantation

Physic

Depositio

vapora

Thermal Evaporator

Deposition is achieved by evaporation

or sublim

ation of heated metal onto

substrate.

This can be done either by resistance

heating or by e-beam bombardment.

Additive Processes

Physic

Depositio

2. Sputtering

Sputtering is achieved by accelerated

inert ion (Ar+) by DC or RF drive in

plasma through potential gradient to

bombard metallic target.

Then the targeting material is

sputtered away and deposited onto

substrate placed on anode.

Additive Processes

Physic

Depositio

Additive Processes

ical V

apor D

epositio

deposited

Polysilicon, silicon nitride (Si3N4), silicon oxide (SiOx), silicon carbide (SiC) etc.

does C

EGaseous reactants are introduced into chamber at elevated temperatures.

EReactant reacts and deposits onto substrate

Types o

LPCVD (Low Pressure CVD), PECVD (Plasma Enhanced CVD)

Salient Featu

ECVD results depend on pressure, gas, and temperature

ECan be diffusion or reaction limited

EVaries from film

composition, crystallization, deposition rate and electrical and

mechanical properties

Dry Etching

ical Etc

HF is a powerful etchantand hence, highly dangerous.

2XeF2+Si→2Xe+SiF4

EIsotropic etching (typically 1-3µm/min)

EDoes not attack aluminum, silicon dioxide, and silicon nitride

Reaction M

echanis

Produce reactive species in gas-phase Reactive species diffuse to the solid

Adsorption, and diffuse over the surface Reaction Desorption

Diffusion

Dry Etching

eactive Ion E

A very high-aspect-ratio silicon etch method

(usually > 30:1)

rocess

EEtch rate is 1.5 –4 µm/min

ESF6 to etch silicon

EApprox. 10nm flourcarbonpolymer (similar

is plasma deposited using C

EEnergetic ions (SF6+) remove protective

polymer at the bottom trench

DRIE Etched Pillars

Wet Etching

Isotropic etchantsetch in all directions

at nearly the same rate.

Commonly use chemical for Silicon is

HNA (HF/HNO3/Acetic Acid)

This results in a finite amount of

undercutting

Wet Etc

active P

rocesses

Wet Etching

Anisotropic etchantsetch much faster

in one direction than in another.

Etchantsare generally Alkali

Hydroxides (KOH, NaOH, CeOH, ..)

ESlower etch rate on (111) planes

EHigher etch rate on (100) and (110)

planes (400 times more faster than

the (111) plane)

ETypical concentration of KOH

is around 40 wt%

Reaction:

Silicon (s) + Water + Hydroxide Ions →

Silicates + Hydrogen

Wet Etc

Metal Patterning

Example

An insulin pump fabricated by classic MEMS technology

(Surface Micromachining)

1. Pumping membrane

2. Pumping chamber

3. Inlet

4. Outlet

5. Large mesa

6. Upper glass plate

7. Bottom glass plate

8. patterned thin layer (for improved fluidics)

MEMS Packaging

Fabrication of

MicrofluidicChannels

Materials

•Silicon / Sicompounds

-Classical MEMS approach

-Etching involved

•Polymers / Plastics

-Newer methods

-primary die yet needed

-easy fabrication of subsequent

components

Etching Methods

Step 1 : Etching of Si

-Isotropic / Anisotropic

-HNA for isotropic

-KOH/EDP/TMAH for

anisotropic

-RIE can also be used

for high aspect ratios

Etching Methods

Step 2 : Closure of channel

a)Bonding another

substrate

b)LPCVD coating

c)Ground Plate Supported

Insulating Channels

Etching Methods

Step 2 : Closure

d) Closing Holes in the

mask material

-channel is defined

by a sequence of

holes.

-channel formed by

underetching

Etching Methods

Step 2 : Closure

e) Burying channels

beneath surface

-Trench made using

-KOH etching to form

microchannels

-Oxide fills trench

A Comparative study

Using Polymers/Plastics

•Imprinting and Hot Embossing

•Injection Molding

•Laser Photoablation

•Soft Lithography

•X ray Lithography (LIGA)

Imprinting/Embossing

•Stamp made in Sior

•Stamp pressed on

Plastic to form

microfluidic channels

•Many common

plastics successfully

imprinted

Soft Lithography

•Elastomericpolymer

cast in a Sistamp and

•Polymer is peeled off

•Channel architecture

thus transferred to the

polymer

•PDMS technology is

becoming popular

Laser Photoablation

•High aspect ratio

channels achievable

•Laser pulses in the

UV region used

•Sealing by thermal

lamination with a

PET/PE film

at 1250C

•Depth controllable

References

http://www.kuos.org/archives/MEMS%20Short%20Course.p

http://mems.colorado.edu/c1.res.ppt/ppt/g.tutorial/ppt.htm

http://mems.cwru.edu/shortcourse/

http://www2.ece.jhu.edu/faculty/andreou/495/2003/LectureNotes/Handout3a_Ph

otolithographyI.pdf

http://www.memsnet.org

Applications

Nitric O

Nanosensor

Nitric Oxide Sensor

tion o

Left: Schematic of the 16-electrode sensor array. Right: Close-up of a

single site. The underlying metal is Au and appears reddish under the

photoresist. The dark layer is C (300µm-x-300µm)

Cartoon of the fabrication sequence for the NO sensor array

A) Bare 4”Siwafer B) 5µm of photoresist was spin-coated on to the surface, followed by a

pre-bake for 1min at 90°C. C) The samples were then exposed through a mask for 16s using

UV light at 365nm and an intensity of 15mW/cm2. D) Patterned photoresist after development.

E) 20nm of Ti, 150nm of Au and 50nm of C were evaporated on. F) The metal on the

unexposed areas was removed by incubation in an acetone bath. G)A 2nd layer of photoresist,

which serves as the insulation layer, was spun on and patterned.H) The windows in the

second layer also defined the microelectrode sites.

A B C DHGFE

Sensor

Calibra

Sensor

Calibra

Multic

hannelN

Record

robes for

Record

Multi-ele

Record

aocula

, “I

cat”

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