Bionanotechnology and Biomedical Devices

at the Birck Nanotechnology Center

4/2/07

Feat

ure

Size

10nm

100nm

1µm

10µm

1nm

0.1nm

100µm

Plant and Animal Cells

Most Bacteria

Min Feature of MOS-T (in 2007)

Virus

ProteinsOne Helical Turn of DNA

Gate Insulator for 100nm MOS-T

Atoms

Top-down

Bottoms-Up

MEMS

Nan

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lefu

nctio

nal

elem

ents

Mic

roEl

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anos

cale

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Integration of biology, chemistry, and medicine at the micro and nanoscale

Apply micro/nano-technology to develop novel devices and systems that have a biomedical impact or are bio-inspired

Diagnostics- Biochips- Q dots, SiNW, CNTs

Therapeutics- Drug Release- Targeted Delivery

Tissue Engineering - 2/3D Cellular Patterning- Organ Development

Bio-inspired Fabrication- DNA/Protein Mediated

Self-Assembly-

Molecular Elect.- Molecules, DNA,

Proteins, Viruses-Biology, Medicine

Micro/Nanotechnology and Systems

Bio-Inspired Materials- Self Healing and Repair- Sense and Response

Micro-devices for Cell Biology

DNA

mRNA

Protei

ns

Protei

n

Interac

tions,

Metabolite

s

Pathway

s

Tissue

Organ

s

Cell-C

ell

Interac

tions

Grand ‘Opportunities’ & Challenges !

• Personalized disease management and point of care sensors (e.g. personalized DNA sequencer)

• Integrated implantable intelligent diagnostics and therapeutics

• Nano/micro Inspired Implants, tissue engineering, and hybrid organ development

• Probe, alter, and repair individual cells - Nanomedicine

Biochip Cartridge

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Microparticles

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Nano-pipettesand probes

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Nano-particles

Secreted proteins

hν1

+-

+-

Viral-basedNano-machines

hν3

hν2

Bionanotechnology ResearchThe Bio-Nano area is the main link between the Birck Nanotechnology Center (BNC) and the Bindley Biosciences Center (BBC) in Discovery Park.

• BioMEMS Lab I (in BNC)• BioMEMS Lab II (in BNC)• MEMS and Microfluidics (in BNC)• BioNano Lab I (in BNC)• BioNano Lab II (in BNC clean room)

• Physiological Sensing Facility (in BBC)• Laboratory of Custom Biopolymer

Synthesis (in BBC)• Flow Cytometery Facilities (in BBC)• Analytical Chemistry and Mass

Spectrometry (in BBC)

Faculty and Researchers• ~ 42 users in the Bionano area (and

increasing)

Faculty Involved: • Demir Akin (BME)• Rashid Bashir (ECE, BME, ME)• Donald Bergstrom (MCMP)• Arun Bhunia (Food Science)• Tim Fisher (ME)• Peixuan Guo (BMS, BME)• Joseph Iruduyaraj (ABE, BME)• Albena Ivanesevic (BME, Chem)• David Janes (ECE)• James Leary (BMS, BME)• Dimitri Peroulis (ECE)• Masa Rao (ME, MSE)• Arvind Raman (ME)• Cagri Savran (ME, ECE, BME)• Alex Wei (Chem)• Babak Ziaie (ECE, BME)• ….

Birck/Bindley Bionano

Birck Nanotechnology Center 2nd floor

Bindley Biosciences

0

Analytical Chemistry 2037

0

Bio-MEMS 1 2077

Biosensors 1 2081

Bio-MEMS 2 (BL2)2043

Nano Chemistry2031

Bio-Nano 1 (BL2) 2087

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QC

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BNC East Wing, Level 2

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AnodicBonding

Fridge

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Freezer

2087A

2087B

air tank

CO2 tank

Notes:- 2087 A is for bacterial culture, 2087B is for mammalian culture- Location of incubators can be changed within the culture rooms- Bench top items not shown above- freezer (-20C & -120C) in galley – exact location not shown

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ical

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Training and key access:monahan@purdue.eduakin@purdue.edu

Research Examples

http://www.vet.purdue.edu/PeixuanGuo/NDC/index.html

40 nm

50 nm

www.purdue.edu/UNS/html4ever/001206.Rossmann.DNAmotor.html

Another 15 faculty from across 6 institution

Ideal example of Collaboration between BNC/BBC

Thrust 1: Incorporation of reengineered motor in lipid vesicles for gene delivery

Thrust 2: mechanistic study of the reengineered nanomotor

Thrust 3: Integration of nanomotor with artificial nanoporous membranes and films

Prof. D. E. BergstromCollaborative Projects

Multilayered Nanoparticles for Cancer TherapyLeary (BME), Knapp(VCS) Funding: DOD, OSC

DNA Carbon Nanotube ComplexesReifenberger (PHYS), Klaunig (IUSM)Funding: Walther Cancer Institute

PNA

Sequence-specific PNAconjugates of therapeutic, imagingagent, targeting reagent payloads

=

5Õ3Õ

DNA FeNanoparticle

Dyed Microspheres for UV Disinfection System CharacterizationBlatchley (CE), Robinson (BMS) Funding: Showalter,City of Los Angeles

Reengineering proteins through synthetic modification of DNADavisson (MCMP), Friedman (BIOL) Funding: NIH

Nanowire BiosensorsBashir, Alam (ECE)Funding NSF, NASA, NIH

UV light

PEGPEG PEGPEG

nanowire

electrode

LW

receptor target

Biotin-derived chromophore forattachment to streptavidin beads

N

N

O

NH2

OO

OO

OMe

OS

HN NH

O

HH N

H

O

O

OSi

OHN

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NeutrAvidin™ coated bead

Development of novel bacterium-mimetic ultraviolet light sensorsCollaborators: D. E. Bergstrom, Ernest R. Blatchley III, & J. Paul Robinson

•Size and mobility characteristics similar to bacteria

•Sensors released to water flow and pass through the UV disinfection zone

•Trajectory in water flow similar to bacteria

•Linear response (increase in fluorescence) to uv light in the dose range lethal to microorganisms

Cell targeting and entry

Intracellular targeting

Therapeutic genesMagnetic or Qdot core(for MRI or optical imaging)

Concept: Smart Nanomedicine Systems with Control of Gene/Drug Delivery within Single Cells

Prof. Leary, et al.

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Targeting molecules (e.g. an antibody, an DNA, RNA or peptide sequence, a ligand, a thioaptamer), in proper combinations for more precise nanoparticle delivery

Biomolecular sensors(for error-checking and/or gene switch)

Leary and Prow, PCT (USA and Europe) Patent pending 2005

The Multi-Step Targeting Process in Nanomedical Systems

Example of multilayered magnetic nanoparticle for in-vivo use

Prow, T.W., Grebe, R., Merges, C., Smith, J.N., McLeod, D.S., Leary, J.F., Gerard A. Lutty, G.A. "Novel therapeutic gene regulation by genetic biosensor tethered to magnetic nanoparticles for the detection and treatment of retinopathy of prematurity" Molecular Vision 12: 616-625, 2006

Concept: Smart Nanomedicine Systems with Control of Gene/Drug Delivery within Single Cells

Prof. Leary, et al.

0.0000.0100.0200.0300.0400.0500.0600.0700.0800.090

10 100 1000 10000 100000 1000000 1E+07Concentration (pM)

1/0

ratio

SAH

Folate binding proteinwith Phil Low Group

S-adenosyl homocysteinewith Dave Thompson Group

Immunomagnetic DiffractometryProf. C. Savran, et al.

30 µm

Manuscript in preparationManuscript in preparation

Cancer Patient 1

Cancer Patient 2

HealthyPerson

Magnetically Enhanced Nanomechanical DetectionProf. C. Savran, et al.

incident laser beam

Photodetector 2

diffraction modes

Magnetic force exerted on superparamagnetic beads

Photodetector 1

SNR

0

10

20

30

40

50

0 10 20 30 40 50

frequency (Hz)

Sign

al to

Noi

se R

atio

3

0

12 2

r

r

d dBF Bdz

μπμ μ

⎛ ⎞−= ⎜ ⎟+⎝ ⎠

•Magnetic beads that have captured target molecules are specifically captured on sensing cantilever surface via secondary antibodies.

•Application of magnetic field bends the sensing cantilever with respect to the reference.

•AC magnetic field can give more than 100 fold higher signal-to-noise ration in comparison with DC actuation: enabled Angstrom level motion detection.

We expect to combine immunomagnetic separation with magnetically-enhanced nanomechanical detection, and fabricate optimal cantilevers that can detect single beads: ultra low target concentrations.

Robust, Titanium-based Microneedles

- Micrometer-scale needles enable painlessinjection & fluid sampling

- Potential applications include improved glucose regulation for diabetes, transdermal drug delivery, novel cancer therapies, and electrodes for neural & epiretinal prostheses

PI : Masa Rao, Schools of Mechanical Engineering & Materials Engineering (by courtesy)

Our specific novelty: Use of titanium addresses key limitations of current Si-based devices (mechanical reliability & biocompatibility)

Integrated Chips for Study of Microorganisms and Cells

“Lab on a Chip” with microfluidics and micro/nanosensors

Glass cover

In/Out ports Cavities/ Wells

Epoxy adhesive

Pin 700µm

Lab-on-a-chip for Detection of Live BacteriaLiu, Park, Li, Huang, Geng,

Bhunia, Ladisch, Bashir

Nanopore Sensors for DNA DetectionChang, Andreadakis, Kosari, Vasmatzis,

Bashir

Dielectrophoresis Filters an Traps for Biological Entities

Li, Akin, Bhunia, Bashir

Micro-Mechanical Cantilevers for Detection

of SporesDavila, Walter, Aronson,

Bashir

Trapping/Lysing of Bacteria/Viruses In

Microfluidic DevicesPark, Akin, Bashir

Nano-Mechanical Cantilever Sensors for Detection of VirusesGupta, Akin, Broyles,

Ladisch, Bashir

Silicon Nanowires and Nanoplates for DNA and

Protein DetectionElibol, Reddy, Nair,

Bergstrom, Alam, Bsahir

Mech/Elect.Detection

DNA, protein

Cantilevers,NanoFETs, Nano-pores

Cell Lysing

Nano-probeArray

Micro-scaleImpedance

Spectroscopy

ViabilityDetection

Conc.Sorting

On-chipDielectro-phoresis

Fluidic Ports

SelectiveCapture

Ab-based

Capture

MEMSFilters

Filters

Nanomechanical Sensors for Viral Detection

Courtesy of Seyet, LLC

A. Gupta, et al. Proc. Nat. Acad. Sci. 2006

Frequency Shift, Δf = 60 kHz ⇒ Mass change, Δm = 9 fg⇒ This corresponds 1 vaccinia virus.

f0 = 1.27 MHz

f1 = 1.21 MHz

Q ~ 5k = 0.006

N/m

Δf=60kHz

Objectives: To develop technology for the rapid detection of virus particles in fluid and air using Nanomechanical Cantilever Sensors

Solid State Nanopore Channels with DNA Selectivity• Frontiers in biology Single molecule detection

(and sequencing) • Biological pores and channels can perform

sensing for genomics, proteomics, and Systems-Biology research

• Nanotechnology-based (top-down/bottoms up) are needed for making these approaches usable, and robust and form arrays of addressable pores.

S. Iqbal, D. Akin, R. Bashir, Nature Nanotechnology, April, 2007

Implantable Wireless Microsystems for Diagnosis and Management of Glaucoma

Prof. Babak Ziaie, et al.

A Micromachined Transponder for Radiation OncologyProf. Babak Ziaie, et al.

Apply micro/nano-technology to develop novel devices and systems that have a biomedical impact or are bio-inspired

Diagnostics- Biochips- Q dots, SiNW, CNTs

Therapeutics- Drug Release- Targeted Delivery

Tissue Engineering - 2/3D Cellular Patterning- Organ Development

Bio-inspired Fabrication- DNA/Protein Mediated

Self-Assembly-

Molecular Elect.- Molecules, DNA,

Proteins, Viruses-Biology, Medicine

Micro/Nanotechnology and Systems

Bio-Inspired Materials- Self Healing and Repair- Sense and Response

Micro-devices for Cell Biology