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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
osca
lefu
nctio
nal
elem
ents
Mic
roEl
ectr
onic
s&
MEM
SN
anos
cale
func
tiona
lel
emen
ts
Mic
roEl
ectr
onic
s&
MEM
S
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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Silicon
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
D (A
cid)
H
S
Lase
r Dop
pler
Vibr
omet
er A
AA
A
AA
AA
AA
AA
C C
AA
AA
A
G
S
DJ A
AA
A
D (s
olve
nt)
NA
A
A A
A A
C
A
SI,
MV A
C
Sol
vent
N
D (S
olve
nt)
A
A
AA
A
A
4x8
Opt
ical
Tab
le
QC
M
CAB
Frid
ge
BL-
2 H
ood
BL-
2 H
ood
SC
C1
Incu
bato
rIn
cuba
tor
CAB
Freezer
H20 Bath
CAB
Dyn
. Lig
ht
SC
C1
KL
SINK
SC
C1
SC
C1
J
BNC East Wing, Level 2
SINK
Enc
losu
re
Enc
losu
re
soft
Lith
o
Auto-Clave
YL, K
PS
B
NW
, PB
AnodicBonding
Fridge
Cabx2
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
4x8
Opt
ical
Tab
le
E (A
cid) N2
GloveBox
DA
A
Enc
losu
reB
L2 H
ood
Enc
losu
reB
L2 H
oodUV
Lig
hts
UV
Lig
hts
UV
Lig
hts
JJC
PD
Cab
DN
A N
anop
ore
F. Cab
BR
, OE
Training and key access:[email protected]@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
O
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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Y
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YY Y
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Y
YY Y
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