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

Friday, May 22, 2009

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

Friday, May 22, 2009

NRG 2009

Outline

Overview of pnc-Si

Transport

Separations

Cell Culture

Other Applications

Friday, May 22, 2009

NRG 2009

Fabrication

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

Friday, May 22, 2009

NRG 2009

Fabrication RAPID = SECONDS

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

Friday, May 22, 2009

NRG 2009

Fabrication RAPID = SECONDS

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

Friday, May 22, 2009

Nanomembrane Research Group [NRG]

physical vapor deposition

6

frontside

Friday, May 22, 2009

Nanomembrane Research Group [NRG]

physical vapor deposition

6

frontsiderf magnetron sputtering

Friday, May 22, 2009

Nanomembrane Research Group [NRG]

physical vapor deposition

6

20 nm sputtered SiO2

15 nm α-Si

frontsiderf magnetron sputtering

Friday, May 22, 2009

Nanomembrane Research Group [NRG]

physical vapor deposition

6

20 nm sputtered SiO2

15 nm α-Si

frontsiderf magnetron sputtering

Friday, May 22, 2009

Nanomembrane Research Group [NRG]

physical vapor deposition

6

20 nm sputtered SiO2

15 nm α-Si

frontsiderf magnetron sputtering

Friday, May 22, 2009

Nanomembrane Research Group [NRG]

physical vapor deposition

6

20 nm sputtered SiO2

15 nm α-Si

frontside

amorphous Si

Friday, May 22, 2009

Nanomembrane Research Group [NRG]

rapid thermal anneal

7

20 nm sputtered SiO2

15 nm α-Si

amorphous Si

frontside

Friday, May 22, 2009

Nanomembrane Research Group [NRG]

20 nm sputtered SiO2

15 nm pnc-Si

rapid thermal anneal

7

700 °C – 1000 °C < 5 minpnc-Si

frontside

Friday, May 22, 2009

Nanomembrane Research Group [NRG]

variety of formats

8

Friday, May 22, 2009

NRG 2009

Sharp Cut-offs and Tunable Pore Sizes

T = 715C

T = 729C

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

NANOCRYSTALS

NANOPORES

Friday, May 22, 2009

Nanomembrane Research Group [NRG]

pore size & density – rtp temperature

10

20 nm sputtered SiO2

15 nm pnc-Si

Friday, May 22, 2009

Nanomembrane Research Group [NRG]

pore size & density – rtp temperature

10

700 C

20 nm sputtered SiO2

15 nm pnc-Si

Friday, May 22, 2009

Nanomembrane Research Group [NRG]

pore size & density – rtp temperature

10

800 C

20 nm sputtered SiO2

15 nm pnc-Si

Friday, May 22, 2009

Nanomembrane Research Group [NRG]

pore size & density – rtp temperature

10

850 C

20 nm sputtered SiO2

15 nm pnc-Si

Friday, May 22, 2009

Nanomembrane Research Group [NRG]

pore size & density – rtp temperature

10

1000 C

20 nm sputtered SiO2

15 nm pnc-Si

Friday, May 22, 2009

Nanomembrane Research Group [NRG]

pore size & density – rtp temperature

10

1100 C

20 nm sputtered SiO2

15 nm pnc-Si

Friday, May 22, 2009

Nanomembrane Research Group [NRG]

controlling morphology – thickness

11

15 n

m p

nc-S

i

Friday, May 22, 2009

Nanomembrane Research Group [NRG]

controlling morphology – thickness

11

15 n

m p

nc-S

i30

nm

pnc

-Si

Friday, May 22, 2009

NRG 2009

Mechanically Robust

200 µm

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

Friday, May 22, 2009

NRG 2009

Mechanically Robust

200 µm

15 PSI

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

Friday, May 22, 2009

NRG 2009

Mechanically Robust

200 µm

15 PSI 0 PSI

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

Friday, May 22, 2009

NRG 2009

Key Biological Sizes

smallsolutes

1 nm 10 nm 1 um

proteins virus bacteria

10 um

eukaryoticcells

Friday, May 22, 2009

NRG 2009

Key Biological Sizes

smallsolutes

1 nm 10 nm 1 um

proteins virus bacteria

10 um

eukaryoticcells

PNC-SI (5-80 NM)

Friday, May 22, 2009

NRG 2009

Key Biological Sizes

smallsolutes

1 nm 10 nm 1 um

proteins virus bacteria

10 um

eukaryoticcells

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

Friday, May 22, 2009

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

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

Size Based Separation

Friday, May 22, 2009

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

Size Based Separation

Friday, May 22, 2009

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

Size Based Separation

Friday, May 22, 2009

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

Size Based Separation

Friday, May 22, 2009

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

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

Size Based Separation

Friday, May 22, 2009

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

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

Size Based Separation

Friday, May 22, 2009

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

--------

--------

------

-

-

---

--

--

-- -

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

Charge Based Separation

Friday, May 22, 2009

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

-

-

---

--

--

-- -

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

Charge Based Separation

Friday, May 22, 2009

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

-

-

---

--

--

-- -

++++++++

++++++++

++++++

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

Charge Based Separation

Friday, May 22, 2009

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

-

-

---

--

--

-- -

++++++++

++++++++

++++++

-

-

---

--

--

-- -

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

Charge Based Separation

Friday, May 22, 2009

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

-

-

---

--

--

-- -

-

-

---

--

--

-- -

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

Charge Based Separation

Friday, May 22, 2009

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

-

-

---

--

--

-- -

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

Charge Based Separation

Friday, May 22, 2009

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

-

-

---

--

--

-- -

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

Charge Based Separation

Friday, May 22, 2009

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

-

-

---

--

--

-- -

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

-

-

---

--

--

-- -

Charge Based Separation

Friday, May 22, 2009

NRG 2009

Scalable, flexible, economical fabrication

Friday, May 22, 2009

NRG 2009

Production Flow

PATTERNING DEPOSITION THERMAL ANNEALING

ETCHING TESTING & APPLICATIONS

PAST

Friday, May 22, 2009

NRG 2009

Production Flow

PATTERNING DEPOSITION THERMAL ANNEALING

ETCHING TESTING & APPLICATIONS

PAST

NEAR FUTURE

ALL FABRICATION TESTING & APPLICATIONS

Friday, May 22, 2009

NRG 2009

Production Flow

PATTERNING DEPOSITION THERMAL ANNEALING

ETCHING TESTING & APPLICATIONS

PAST

NEAR FUTURE

ALL FABRICATION TESTING & APPLICATIONS

MADE POSSIBLE BY PURCHASE OF NEW SYSTEMS

• SURFACE PREP• ANNEALING • DEPOSITION

Friday, May 22, 2009

NRG 2009

UR’s Nanoscience Center

Friday, May 22, 2009

NRG 2009

UR’s Nanoscience Center

MCGRATH LAB

Friday, May 22, 2009

NRG 2009

UR’s Nanoscience Center

MCGRATH LAB

SURFACE PREP, DEPOSITION AND

ANNEALING

Friday, May 22, 2009

NRG 2009

UR’s Nanoscience Center

MCGRATH LAB

SURFACE PREP, DEPOSITION AND

ANNEALING

LITHOGRAPHY

Friday, May 22, 2009

NRG 2009

Manufacturing Possibilities and Challenges

4” wafer

CURRENTLY: 68 INSERTS PER WAFER

Friday, May 22, 2009

NRG 2009

Manufacturing Possibilities and Challenges

4” wafer

CURRENTLY: 68 INSERTS PER WAFER

6” wafer

> 500 INSERTS PER WAFER

Friday, May 22, 2009

NRG 2009

Manufacturing Possibilities and Challenges

0.004 CM2

0.33 CM2

Friday, May 22, 2009

NRG 2009

Manufacturing Possibilities and Challenges

0.004 CM2

0.33 CM2

• LESS THAN 1% OF AREA IS CURRENTLY ACTIVE

• MADE NECESSARY BY ETCHING, MECHANICS, AND DEFECT FREQUENCY

Friday, May 22, 2009

NRG 2009

Manufacturing Possibilities and Challenges

0.004 CM2

0.33 CM2

• LESS THAN 1% OF AREA IS CURRENTLY ACTIVE

• MADE NECESSARY BY ETCHING, MECHANICS, AND DEFECT FREQUENCY

200 microns

Friday, May 22, 2009

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)

Friday, May 22, 2009

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

Friday, May 22, 2009

NRG 2009

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

Friday, May 22, 2009

NRG 2009

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

Friday, May 22, 2009

NRG 2009

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

k = 2DNr

Friday, May 22, 2009

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.

Friday, May 22, 2009

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.

Friday, May 22, 2009

NRG 2008

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

Friday, May 22, 2009

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

Friday, May 22, 2009

NRG 2009

Cellular Transwell DevicesCO-CULTURE

Friday, May 22, 2009

NRG 2009

Cellular Transwell DevicesCO-CULTURE

DRUG PERMEATION

Friday, May 22, 2009

NRG 2009

Microfluidics

Friday, May 22, 2009

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 …

Friday, May 22, 2009