molecular and cellular applicationsewh.ieee.org/r1/syracuse/embsweb/archives/events/... · 2009. 5....

Silicon nanomembranes (pnc-Si): Molecular and Cellular

applications James L. McGrathBiomedical EngineeringUniversity of RochesterNanomembrane Research Group

EMBS @ SY!CUSE UNIVERSITY APRIL 23, 2009

Friday, May 22, 2009

NRG 2009

Silicon Nanomembranes(pnc-Si - porous nanocrystalline silicon)

Thinner = faster transport and less sample loss

A. van den Berg and M. Wessling, Nature 445, 726, 2007

15nm thick5-80 nm pores


NRG 2009

Chris Striemer*

Bioengineeing Group Materials Group

Tom Gaborski*

Jess Snyder (Protein separations)Anant Agrawal (Cellular studies)Barrett Nehilla (Cell applications)Henry Chung (Microfluidics)Crowe, Hoffman, Summers (undergraduates)

Dave Fang (Material development)Maryna Kavalenka (Air permeability)

Jim McGrath Philippe Fauchet

SiMPore Inc.*

JP DesormeauxKarl Reisig

Nakul Nataraj

Rick RichmondJamie RoussieFunding

NSF, NIH, CSTI, J&J, NYSTAR, CEIS

Collaborations

Shigeru Amemiya, PITT

Nanomembrane Research Group

RIT: SMFL

Bill Bernhard, URMC


http://Nanomembranes.org

http://Nanomembranes.org

NRG 2009

Outline

Overview of pnc-Si

Transport

Separations

Cell Culture

Other Applications


NRG 2009

Fabrication

Striemer, C.S, et al. 2007, Nature, 445:749-53


NRG 2009

Fabrication RAPID = SECONDS



Nanomembrane Research Group [NRG]

physical vapor deposition

6

frontside




6

frontsiderf magnetron sputtering




6

20 nm sputtered SiO2

15 nm α-Si

frontsiderf magnetron sputtering




6


15 nm α-Si

frontside

amorphous Si



rapid thermal anneal

7


15 nm α-Si

amorphous Si

frontside




15 nm pnc-Si

rapid thermal anneal

7

700 °C – 1000 °C < 5 minpnc-Si

frontside



variety of formats

8


NRG 2009

Sharp Cut-offs and Tunable Pore Sizes

T = 715C

T = 729C


NANOCRYSTALS

NANOPORES



pore size & density – rtp temperature

10


15 nm pnc-Si




10

700 C


15 nm pnc-Si




10

800 C


15 nm pnc-Si




10

850 C


15 nm pnc-Si




10

1000 C


15 nm pnc-Si




10

1100 C


15 nm pnc-Si



controlling morphology – thickness

11

15 n

m p

nc-S

i



controlling morphology – thickness

11

15 n

m p

nc-S

i30

nm

pnc

-Si


NRG 2009

Mechanically Robust

200 µm



NRG 2009

Mechanically Robust

200 µm

15 PSI



NRG 2009

Mechanically Robust

200 µm

15 PSI 0 PSI



NRG 2009

Key Biological Sizes

smallsolutes

1 nm 10 nm 1 um

proteins virus bacteria

10 um

eukaryoticcells


NRG 2009


smallsolutes

1 nm 10 nm 1 um


10 um

eukaryoticcells

PNC-SI (5-80 NM)


NRG 2009


smallsolutes

1 nm 10 nm 1 um


10 um

eukaryoticcells

PNC-SI (5-80 NM)@ 0.1%-15%


NRG 2009

3 L fluorescent mixture (PBS)

glass co

versl

ipPBS buffer

15 nm thicknc-Si membrane

Species 1 -

50 m silica spacer

Species 2 -

~ 500 mmicroscope

experimentalfield of view

t = 0 min

100 m


Size Based Separation


NRG 2009Striemer, C.S, et al. 2007, Nature, 445:749-53



NRG 2009

Time, min0 1 2 3 4 5 6 7

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

0

Flu

ores

cenc

e in

tens

ity, a

.u.

BSA

Alexa dye

1 nm

7 nm

MEMBRANE A




NRG 2009

Time, min0 1 2 3 4 5 6 7

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

0

Flu

ores

cenc

e in

tens

ity, a

.u.

BSA

Alexa dye

1 nm

7 nm

MEMBRANE A

Time, min0 1 2 3 4 5 6 7

BSA

IgG

0.4

0.3

0.2

0.1

0

Flu

ores

cenc

e in

tens

ity, a

.u.

7 nm

14 nm

MEMBRANE B




NRG 2009

Alexa dye - charge = 2-

0 1 2 3 4 5 6 7 8 9 10

0.45

0.40

0.35

0.30

0.25

0.20

0.15

0.10

0.05

0

Time, min

Flu

ores

cenc

e in

tens

ity, a

.u.

Amine - DI H2O

Oxide - 100 mM NaCl

Oxide - DI H2O

--------

--------

------

-

-

---

--

--

-- -


Charge Based Separation


NRG 2009


0 1 2 3 4 5 6 7 8 9 10

0.45

0.40

0.35

0.30

0.25

0.20

0.15

0.10

0.05

0

Time, min

Flu

ores

cenc

e in

tens

ity, a

.u.

Amine - DI H2O

Oxide - 100 mM NaCl

Oxide - DI H2O

-

-

---

--

--

-- -




NRG 2009


0 1 2 3 4 5 6 7 8 9 10

0.45

0.40

0.35

0.30

0.25

0.20

0.15

0.10

0.05

0

Time, min

Flu

ores

cenc

e in

tens

ity, a

.u.

Amine - DI H2O

Oxide - 100 mM NaCl

Oxide - DI H2O

-

-

---

--

--

-- -

++++++++

++++++++

++++++




NRG 2009


0 1 2 3 4 5 6 7 8 9 10

0.45

0.40

0.35

0.30

0.25

0.20

0.15

0.10

0.05

0

Time, min

Flu

ores

cenc

e in

tens

ity, a

.u.

Amine - DI H2O

Oxide - 100 mM NaCl

Oxide - DI H2O

-

-

---

--

--

-- -

++++++++

++++++++

++++++

-

-

---

--

--

-- -




NRG 2009


0 1 2 3 4 5 6 7 8 9 10

0.45

0.40

0.35

0.30

0.25

0.20

0.15

0.10

0.05

0

Time, min

Flu

ores

cenc

e in

tens

ity, a

.u.

Amine - DI H2O

Oxide - 100 mM NaCl

Oxide - DI H2O

-

-

---

--

--

-- -

-

-

---

--

--

-- -




NRG 2009


0 1 2 3 4 5 6 7 8 9 10

0.45

0.40

0.35

0.30

0.25

0.20

0.15

0.10

0.05

0

Time, min

Flu

ores

cenc

e in

tens

ity, a

.u.

Amine - DI H2O

Oxide - 100 mM NaCl

Oxide - DI H2O

-

-

---

--

--

-- -




NRG 2009


0 1 2 3 4 5 6 7 8 9 10

0.45

0.40

0.35

0.30

0.25

0.20

0.15

0.10

0.05

0

Time, min

Flu

ores

cenc

e in

tens

ity, a

.u.

Amine - DI H2O

Oxide - 100 mM NaCl

Oxide - DI H2O

-

-

---

--

--

-- -

NaClStriemer, C.S, et al. 2007, Nature, 445:749-53



NRG 2009


0 1 2 3 4 5 6 7 8 9 10

0.45

0.40

0.35

0.30

0.25

0.20

0.15

0.10

0.05

0

Time, min

Flu

ores

cenc

e in

tens

ity, a

.u.

Amine - DI H2O

Oxide - 100 mM NaCl

Oxide - DI H2O

-

-

---

--

--

-- -

NaClStriemer, C.S, et al. 2007, Nature, 445:749-53

-

-

---

--

--

-- -



NRG 2009

Scalable, flexible, economical fabrication


NRG 2009

Production Flow

PATTERNING DEPOSITION THERMAL ANNEALING

ETCHING TESTING & APPLICATIONS

PAST


NRG 2009

Production Flow



PAST

NEAR FUTURE

ALL FABRICATION TESTING & APPLICATIONS


NRG 2009

Production Flow



PAST

NEAR FUTURE

ALL FABRICATION TESTING & APPLICATIONS

MADE POSSIBLE BY PURCHASE OF NEW SYSTEMS

• SURFACE PREP• ANNEALING • DEPOSITION


NRG 2009

UR’s Nanoscience Center


NRG 2009


MCGRATH LAB


NRG 2009


MCGRATH LAB

SURFACE PREP, DEPOSITION AND

ANNEALING


NRG 2009


MCGRATH LAB

SURFACE PREP, DEPOSITION AND

ANNEALING

LITHOGRAPHY


NRG 2009

Manufacturing Possibilities and Challenges

4” wafer

CURRENTLY: 68 INSERTS PER WAFER


NRG 2009


4” wafer

CURRENTLY: 68 INSERTS PER WAFER

6” wafer

> 500 INSERTS PER WAFER


NRG 2009


0.004 CM2

0.33 CM2


NRG 2009


0.004 CM2

0.33 CM2

• LESS THAN 1% OF AREA IS CURRENTLY ACTIVE

• MADE NECESSARY BY ETCHING, MECHANICS, AND DEFECT FREQUENCY


NRG 2009


0.004 CM2

0.33 CM2

• LESS THAN 1% OF AREA IS CURRENTLY ACTIVE

• MADE NECESSARY BY ETCHING, MECHANICS, AND DEFECT FREQUENCY

200 microns


NRG 2009

Ultrathin SiN membranesTong, et al. (2004). Silicon Nitride Nanosieve Membrane. Nano Letters 4, 283-287

SiN - 10 nm thick but elaborate and impractical

No demonstrated separations

Appreciated all the potential and issues (air flow, water permeability, and mechanics)


NRG 2009

10 µm-diameter tip Ru(NH3)63+ in 0.1 M KCl

High Diffusive PermeabilityInstrinsic permeability of 5.2 x 10-2 cm/s measured using Scanning Electrochemical Microscopy.

Experimental results & pore histograms are consistent with theory that neglects pore resistance

Between 2-3 orders higher than small molecule diffusion permeability of reconstituted cellulose or PES.

Kim et al. 2008, JACS 130:4230-4231

Shigeru Amemiya


NRG 2009




Kim et al. 2008, JACS 130:4230-4231

Shigeru Amemiya


NRG 2009




Kim et al. 2008, JACS 130:4230-4231

Shigeru Amemiya

k = 2DNr


NRG 2008

Higher Permeability = Smaller ...

For current devices: active area is 1.8 m2 and transmembrane water flow is ~10 ml/min @ 3 psi.

1000x improved permeability would require only 18 cm2. So 10 dime-sized membranes with mostly (~80%) active area could support both transmembrane flow and match dialysis in the same period of time.


NRG 2008

… or faster?Alternatively a 6” wafer of mostly active membrane could achieve the same dialysis in 1/10th of the time.


NRG 2008

… or faster?Alternatively a 6” wafer of mostly active membrane could achieve the same dialysis in 1/10th of the time.

THE MATERIAL PROVIDES THE POTENTIAL

REALIZING THIS POTENTIAL IS AN ENGINEERING CHALLENGE


NRG 2009

Cellular Transwell DevicesCO-CULTURE


NRG 2009

Cellular Transwell DevicesCO-CULTURE

DRUG PERMEATION


NRG 2009

Microfluidics


NRG 2009

ConclusionsPnc-Si is a new ultrathin nanoporous membrane material. Small membranes can be manufactured on a large scale and incorporated into practical separation devices.

Primary application is to small scale separation of biologicals

High air and liquid permeabilities w/ demonstrated ability to fractionate proteins, nanoparticles, etc.

Viable as a cell-culture substrate. Cell behavior on membranes is normal.

Microfluidics, arrayed membranes for screening applications, electrokinetics, and more …


molecular and cellular applicationsewh.ieee.org/r1/syracuse/embsweb/archives/events/... · 2009. 5....

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