Interfacing Biology and Engineering at the Micro and Nano Scale · 2017-01-26 · Interfacing Biology and Engineering at the Micro and Nano Scale March 8th, 2008 ... * Size information

1

Interfacing Biology and Engineering at the Micro and Nano Scale

March 8th, 2008Institute of Biological Engineering

2008 Annual Conference

Rashid BashirMicro and Nanotechnology Laboratory

Electrical and Computer Engineering & BioEngineeringUniversity of Illinois, Urbana-Champaign

http://libna.micro.uiuc.edu/

2

AcknowledgementsResearchers:• Prof. Demir Akin• Dr. JeongMi Moon• Piyush Bajaj• Vincent Chan• Brian Dorvell• Oguz Elibol• Yi-Shao Liu• Kidong Park• Bobby Reddy• Shuaib Salamat• Murali Venkatesan• Nick Watkins

Recent Alums• Prof. J. Jang, Prof. S. Iqbal, Prof. S.

W. Lee, Prof. L. Yang,

BioVitesse, Inc. Co-Founder

Faculty Collaborators– Prof. A. Alam (ECE, Purdue)– Prof. D. Bergstrom (Med Chem, Purdue)– Prof. A. Bhunia (Food Science, Purdue)– Prof. S. Claire (IU-SOM)– Prof. P. Guo (Vet Medicine, BME, Univ. of

Cincinnati)– Prof. M. Ladisch (Ag& Bio Engr, Purdue) – Prof. M. Toner (Harvard Med School)– Prof. J. P. Robinson (BMS, BME, Purdue)– Prof. W. Rodriguez (Harvard Med School)

Funding Agencies• National Institute of Health, NIBIB• NASA Institute on Nano-electronics and Computing

(INAC)• US Department of Agriculture (Center for Food

Safety Engineering at Purdue)• NSF NSEC at OSU• NIH Nanomedicine NDC

BBBB

On Size and Scale !Fe

atur

e Si

ze

10nm

100nm

1µm

10µm

1nm

0.1nm

100µm

1mm

10mm

100mm

3Bottoms-UpChemical

CNT, QD,NS, NWs, AAO

35nm Feat.of MOS-T

(in 2008)

Gate Insulator

Top-Down Fabrication

MEMS

Mic

roel

ectro

nic

and

ME

MS

Nano-pores

System on A board

System on a chip

Nan

oele

ctro

nics

an

d N

anos

cale

S

enso

rs

Most Bacteria

Virus

ProteinsHelical Turn of DNA

Bottoms-UpBiological

C-C Bond

Ants

Tissue

Organs

Plant and Animal Cells

Evolution of Technologies

4

Modern BiologyBiotechnology

Personalized DNA Sequencers

Molecular Basis of Disease

Probe, alter, and repair individual cells –

Nanomedicine and systems biology

Personalized Implantable Diagnostics and

Therapeutics

Hybrid Biodevices & Organs

Biochip Cartridge

N+N+

YYYYYYYYYYY

YYYYYYYYYYYYY

YY

YY

YY

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Silicon

Microparticles

Y Y

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Y Y

YY YY YY Y Y

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Y Y

YY YY YY

Y Y

YY YY YY

Y Y

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Y Y

YY YY YY

Y Y

YY YY YY

Nano-pipettesand probes

Y Y

YY YY YY

Y Y

YY YY YY

Y Y

YY YY YY

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YY YY YY

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Y Y

YY YY YY

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Y Y

YY YY YY

Nano-particles

Secreted proteins

hν1

+-

+-

Viral-basedNano-machines

hν3

hν2

55

Research Projects

Micro/Nano-biosensorsand Lab-on-Chip

Cell Biology and Tissue

Engineering

Nanoscale Therapeutics and

Nanomedicine

• 3-D Tissue Engineering with Stereo-Lithography

• Nanomechanics for Cell Biology

• Petri dish on a chip with electrical detection• Cantilevers for virus and bacterial detection• Detection of CD4+ cells from blood• Nanopores for single DNA molecule characterization• Label free field effect silicon sensors for DNA and proteins

• Bacterial Mediated Delivery of Nanoparticles• Macrophage Stealth Delivery of Nanovectors• Phi-29 Nanomotor for Nanomedicine

www.micro.uiuc.edu/LIBNA

6

Microfluidic-based technology platforms for bacterial detection

R. Bashir, ECE, BME A. Bhunia, Food Science M. Ladisch, BME, ABEJ. P. Robinson, BMS, BME

L. MonocytogenesOn a chip

• Rapid detection of live bacteria has wide applications– Industrial Microbiology (Pharmaceutical facility monitoring,

Food Safety)– Blood transfusion– Human Diagnostics– Global Health

• Rapid time to result limited by: – Amplification, enrichment, culture– 48-72 hours for growth and identification

• Center for Food Safety Engineering at Purdue (www.cfse.purdue.edu) through cooperative agreement with USDA-ARS

StartingSample

Sample PrepConcentration

Detection/ID

Data Analysis/Results

Overall Approach

~ 30 min ~ 1- 3 hr

Electrical Detection of cell Growth

On-ChipConcentration

1000X

~ 15 - 30 min

Automated Off-ChipCell Concentration And

Recovery - 1000X

Sample100 – 250 ml

~ 1- 3 hr

Electronic Biomolecular identification

8

Integrated Chips for Study ofMicroorganisms 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./Optical

DetectionDNA, 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

hν

9

Overall Detection Scheme

Biotinylated Antibody (C11E9)

SiO2 surface

~14 nm

Streptavidin

Biotinylated BSA

~10 nm

~4 nm

Streptavidin

Biotinylated BSA

~10 nm

~4 nm

* Size information are obtained from Biochemistry 2nd

edition, R. H. Garrett and C. M. Grisham, 1995.

Gomez, Morisette, Bashir, IEEE/ASME JMEMS, 2005Yang, Li, Akin, Huang, Bhunia, Ladisch, Bashir, Lab Chip, 2006

10

Bacterial Growth & Impedance Microbiology !

Invented in late 1800s (Petri and Koch)Still the most widespread means to

grow and detect the presence of bacteria !

# of

bac

teria

Time

Lag phase

Stationary phase

Gro

wth

pha

seEnergy

Metabolism

SugarsOxygen

Na+ATP

OtherProcesses

CO2

Carbonic Acid

H2O

IonChannels

Lactic AcidAcetic Acid

Cell

K+

Na+ ZOwicki et al., Biosens. Bioelectron. (1992)

1.1

1.2

1.3

1.4

1.5

1.6

1.7

0 2 4 6 8 10 12 14 16 18 20 22 24

Time (h)

Cond

uctiv

ity (m

S/c

m)

a

b

c

f

g

e

d

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

0 2 4 6 8 10 12 14 16 18 20 22 24

Time (h)

pH

g f e d c b

a

(A)

(a) no cell, (b) 2.5 x102, (c) 2.39x103, (d) 2.64x104, (e) 2.66x105, (f) 2.65x106, (g) 2.7x107 CFU/ml.

pH

Yang, L, Banada, P., Bhunia, A. Bashir, R., Biotech Bioengr, 2005

Conductivity

11

Petri Dish-on-a-Chip

PC boardw. heater

Wire-bond(with epoxy)

Micro-fluidicTubes

Micro-fluidicTubes

Edge Connector

MicroscopeObjective

BioChip

Measurementelectrodes

DEP captureelectrodes

Outlet Inlet

Measurementelectrodes

DEP captureelectrodes

Outlet Inlet

R. Gomez, D. Morisette, R. Bashir, IEEE/ASME JMEMS, 2005

12

Bacterial Cell Concentration on-Chip

• DEP-based concentration system collects particles from a large flow stream and diverts them to a smaller stream

Inlet

MainOutletDeviation

Outlet

DEP deviation electrodes

DEP electrodes(w. Abs and

growth detection)Fluid and Particles

(low flow)

Fluid only(large flow, no particles)

Fluid and particles

(large flow)

Fluid only(low flow, no

particles)

R. Gomez, D. Morisette, R. Bashir, IEEE/ASME JMEMS, 2005

102 103 104 105 106103

104

105

106

Mag

nitu

de [ Ω

]

Fits to incubation of L. innocua (~3x107 ml-1) in TA4-B6

Ch. 2. Well WB2. 39C.

102 103 104 105 106-60

-50

-40

-30

-20

-10

Frequency [Hz]

Ang

le [D

egre

es]

Meas. (2) 10/16/02. Fit (8) 10/24/02

Time

On-Chip Incubation of L. innocua in LB BrothInitial concentration: ~3x107 cfu/ml

Measured Impedance

Fitted circuit model

Time

On-Chip Incubation of L. Monocytogenes

90%

110%

130%

150%

170%

190%

210%

230%

250%

270%

290%

310%

330%

350%

0 2 4 6 8 10 12 14 16 18 20Time [hours]

Rel

ativ

e Ad

mitt

ance

at 1

00H

z

96%

96%

97%

97%

98%

98%

99%

99%

100%

100%

101%

1 cfu (1) 7/20/0234 cfu (1) 6/25/029 cfu (2) 3/21/02

Approximate number of colony-forming-units (cfu) in a 5.27nl volume:

95%

100%

105%

110%

115%

120%

125%

130%

0 2 4 6 8 10 12 14 16 18 20Time [hours]

Rel

ativ

e C

ondu

ctan

ce

1 cfu9 cfu34 cfu

Approximate number ofcolony-forming-units (cfu)in a 5.27nl volume: Growth

GrowthGrowth

ZwZw ZwZw

Cdi

Rs

Dielectric capacitance

Electrolyteresistance

Electrode-electrolyte interfaces

Electrode-Electrolyte

Interface Model:

Constant-angleimpedance

BjZ nw )(

1ω

=

14

In-process Rapid Detection & Identification of Live CellsBioVitesse, Inc.

• ‘Petri dish on a chip’ to miniaturize impedance microbiology• To quickly and reliably detect and identify live bacteria in 2 to 4 hours, instead of 2 to 10 days• Provides in-process quality control monitoring systems• To the industrial microbiological market (Bio/Pharma and Food Safety)

BioVitesse, Inc. Company Confidential

SiliconBiochip

Chip Cartridge

CCRTM

Cartridge

Automated System

Sample, Media,Sanitizing Fluid

15

Transcription factors:Proteins that control the transcription of specific genes

DNA

mRNA

Proteins

Transcription

Translation

CellDNA

mRNA

Proteins

Transcription

Translation

Cell

DNA – the code of life in all Cells!

http

://w

ww

.chr

omos

ome.

com

/dna

.htm

l

Molecular Biology of the Cell, Alberts, Bray, et al.

16

•α-hemolysin channel, a biological protein based-pore

• Diameter of 2.6 nm.• Translocation of ssDNA using electrophoresis

• Nanoscale coulter counter

Poly-CPoly-A

Nanopores for single DNA molecule characterization

[Service, 2006]

2c/bp x 3e9bp = $60M !

α-hemolysin nanochannel

The model of DNA passing through an α-hemolysin channel.

Kasianowicz et al., 1996, Meller, et. al. 2000.

17

Nanopore FabricationKey steps

• EBL to write dots• TMAH etch• Pore in SOI• Oxidation• Shrinking in TEM

All Images at 1,000,000X. (NPC-2)

Oxide ~800 Å

Oxide ~800 Å

Poly-Si ~1.6 m

ZEP e-beam resist

~80 nm

~80 - 100 nm

230-240 nm

Si 2024Å

BOX 3777 Å

Si Handle layer

Handle layer etched through from back side

Adding DNA Selectivity to Solid State Nanopores

Nanopores with selectivity towards specific targets

Protein Ion Channels

[Kasianowicz et al., 2006]

19

Selective Nanopores Measurements Overview

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

Time

I b

20Si SiO2

Courtesy of Seyet, LLC

One-base Mismatch Perfect Complementary

21

Single-Base Mismatch Selectivity

• Channel-Molecular Interaction– MM-DNA vs. PC-DNA

• PC-DNA– Interactions with Binding Sites– Faster and More than MM-DNA

• MM-DNA– Electrostatic Friction – Mechanical Resistance– Inability to open HPL

PCMM

Time

I b

XX

X

1 2( )nJ c cτ

= −

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

22

Channel Interaction Attractive vs. Repulsive Potential

Key Assumptions• PC/HPL: Attractive Potential • MM/HPL: Repulsive Potential• Magnitudes of Potentials • φ span part of the channel

(a) (b)

(a) Attractive potential (b) Repulsive potential, spanning part of the channel

MM PCMM

PC

eφ φττ

−=

23

• Miniature DNA analyzer – Transduction events at single

molecule, nanoscale– Interface to the macroscale – Array of nanopores – serial or

parallel ?– Site selective functionalization

strategy

• Sequencing by digestion– Smaller molecules – bases !– Digest and detect

Nanopore Channel Sensor Array for Characterization of Single Molecules

24

Piezoelectric Driven

Thermal Noise

Spectra

Cantilever Beam Length = 10 µm

Thickness = 30 nm

f0 = 270 kHz

Mass Change DetectionMass Change Detection

Microcantilever Mass Sensors

Unloaded Resonant Frequency :

Spring constant for a rectangular

shaped cantilever beam:

∗=

mkf

π21

0

3

3

4lwEtk =

⎟⎟⎠

⎞⎜⎜⎝

⎛−=∆ 22

12

114 off

kmπ

• k = spring constant• m = mass of cantilever• f0 = unloaded resonant frequency• f1 = loaded resonant frequency

⎟⎟⎠

⎞⎜⎜⎝

⎛−=∆ 22

12

114 off

kmπ

• k = spring constant• m = mass of cantilever• f0 = unloaded resonant frequency• f1 = loaded resonant frequency

Loaded Resonant frequency :

δm is the added massmm

kfδπ +∗

=21

1

25

Nanomechanical Sensors for Viral Detection

Courtesy of Seyet, LLC

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

Frequency Shift, ∆f = 60 kHz ⇒ Mass change, ∆m = 9 fg ⇒ This corresponds 1 vaccinia virus.

f0 = 1.27 MHz

f1 = 1.21 MHz

Q ~ 5k = 0.006

N/m

∆f=60kHz

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

Living Cantilever Arrays

Microfluidic cell culture array

Selective Functionalization on suspended structure

Cantilever Mass Sensing

a b c d

Measuring the growth-rate of a single cell, under various combination of stimuli.

Cantilever mass sensing µ-fluidic cell culture array

L. P. Lee (UCB)

27

Cell Attachment on Cantilevers• DEP Assisted Capture

Hela cells, captured with DEP. Conductive silicon electrode generate DEP forces to

capture Hela cells.

Vac

PDMS Cover

Silicon SOI Substrate

Silicon CantileverIn SOI layer

oxide

Metalcell

DEP Off DEP On


0 hr 8 hr 18 hr

288um2 8um

Volume: 2349 um3

Density3: 1.055g/cc Estimated mass :

2.48 ng33.95KHz

36.68KHzCalculated

Mass: 2.06 ng

29


Point of Test Biosensors

• Focus on translation: Top-down integrated nano-structures and nano-sensors platforms – POC sensors for biomolecules

• Chip makers and diagnostic industry• System level fabrication and modeling/simulations (from ‘molecules to

systems’) with considerations of integrated systems, fluid and biomolecule transport, packaging and interfaces, etc.

Abbott/iSTAT(Glucose)

Accuteck(LDH, Theophylline)

Abbott/iSTAT(gases, ions, markers) Pregnancy Tests

Silicon Based BioChips !• Disposable, one-time-use devices• Rapid, sensitive, integrated• Detection and monitoring of disease and

state of healthNanowire

sensor

DNA or RNAMolecules

Source Drain

Gate

Functionalized Nanosensor Array

Nanowiresensor

DNA or RNAMolecules

Source Drain

Gate



31

Bio-inspiredMaterials

Diagnostics

Therapeutics

Tissue Engineering

Bio-inspired Fabrication

Bio-Electronics

Apply micro-systems and nanotechnology to develop novel devices and systems that have a biomedical impact or are bio-

inspired

BioMEMS and Bionanotechnology

Micro-devices forCell Biology

Biology, Medicine

Micro & Nanotechnology

and Systems

32

3 µm 4 µm 5 µm 6 µm 7 µm 8 µm 9µmLength of cantilever beam ( µm)

Width of cantilever beam = 1 µm

Thickness of cantilever beam = 10 nm

10 µm3 µm 4 µm 5 µm 6 µm 7 µm 8 µm 9µmLength of cantilever beam ( µm)

Width of cantilever beam = 1 µm

Thickness of cantilever beam = 10 nm

10 µm

Minimum Detectable Mass

The frequency measurement is limited by thermo-mechanical noise on the cantilever beam.

Minimum Detectable Frequency, ∆f,min =

Minimum Detectable Mass, ∆m,min =

kB = Boltzmann constantT = Temperature in KelvinB = Bandwidth measurement, (= 2πf0/2Q)

Q can increase by 100X by driving the cantilevers

kQTBkf

AB

π21 0

43

4541k

mQ

TBkA

effB

Virus Mass Range

Q=5

Q=500

Bacteria

DNA bp ~ 10-21 g100kDa Protein ~ 10-19 g

Roukes, et. al.

34

40nm NPs in KB Cancer Cells

• Bead incubation for 1 hour

• Particles are internalized by cells

• External beads rinsed and quenched by trypan blue dye

One cross-sectionthrough a cell

35

200nm Beads in KB Cells

3-D confocalreconstruction

• Bead incubation for 1 hour

• Confocal images – NPs are NOT internalized

• Cross-sectional scans

One cross-sectionthrough one cell

36

Cell Concentration and Recovery

Chen, et al. Biotech Bioengr, 2005Huang, et al. Submitted, 2007

• Proprietary technology for cell concentration and recovery in small volumes – CCRTM kit

• One-time use filter cartridge• Recovery rates ~ 50%

Ladsich, et al. USDA Review, 2004

Massaged Hotdog Experiment

Automated CCRSystem

37

Recovery Results

Huang, Chen, Ladisch, et al. 2007 (submitted)

100 ml sample in PBST

67.0%0.0±0.0%0.2±0.1%4.0±1.1%3267±153162.8±14.7%3852±123

65.5%0.0±0.0%0.5±0.3%2.9±1.6%3233±80862.2±15.5%4052±122

77.7%0.0±0.0%0.4±0.1%4.9±0.9%3767±60372.4±11.6%4652±121

Total recovery (3 collections)

Leakage through

permeate side

Recovery collection 3

(viable cells)


(viable cells)

Total cells in collection 1


(viable cells)

Final pressure drop (psi)

Initial cell conc.

(cells/ml)

Run#

E. coli

68.2%0.0±0.0%6.0±0.6%25.1±2.6%2303±24337.2±3.9%2866±223

75.9%0.0±0.0%2.3±0.7%13.7±2.4%3717±24460.0±3.9%3066±222

70.2%0.0±0.0%0.9±0.4%12.7±2.4%3510±23656.6±3.8%3166±221


Leakage through

permeate side


(viable cells)


(viable cells)



(viable cells)

Final pressure drop (psi)

Initial cell conc.

(cells/ml)

Run#

Listeria innocua

65.5%0.0±0.0%2.9±0.5%6.4±0.3%6133±181556.2±16.6%40109±243

56.9%0.0±0.0%2.4±0.3%17.3±0.9%4067±90737.3±8.3%40109±242

61.0%0.0±0.0%1.7±0.3%5.6±2.4%5867±20853.7±1.9%40109±241


Leakage through

permeate side


(viable cells)


(viable cells)



(viable cells)

Final pressure

drop (psi)

Initial cell conc.

(cells/ml)

Run#

65.5%0.0±0.0%2.9±0.5%6.4±0.3%6133±181556.2±16.6%40109±243

56.9%0.0±0.0%2.4±0.3%17.3±0.9%4067±90737.3±8.3%40109±242

61.0%0.0±0.0%1.7±0.3%5.6±2.4%5867±20853.7±1.9%40109±241


Leakage through

permeate side


(viable cells)


(viable cells)



(viable cells)

Final pressure

drop (psi)

Initial cell conc.

(cells/ml)

Run#

Streptococcus faecalis

Targeted Nano-therapeutics

Objective:To develop novel means to deliver nano-therapeutics to cancer cells and tumors

• Current drugs are ineffective at penetrating to the tumors due to inadequate vascularization at these tumor sites.

• Nanoparticles have the similar challenge of reaching tumor sites if adequate vascularization does not exist.

• Penetrate multiple barriers

• Need active transport to the cells and tumors

Cancer cells

38

Ferrari, 2005

39

Bacteria as a carrier !

Bacterial Mediated Delivery of Nano-particles in Cells

Objective: To develop biologically-inspired intelligent devices for intracellular monitoring and therapeutic intervention of signal transduction networks

D. Akin, J.P. Robinson, S. Muhammad, A. Bhunia, R. Bashir

• Current drugs are ineffective at penetrating through the solid tumors due to inadequate vascularization at these tumor sites.

• Nanoparticles have the similar challenge of reaching tumor sites if adequate vascularization does not exist since they are carried by blood flow.

• Intracellular bacteria may provide means to penetrate and deliver therapeutic compounds to solid tumors that are otherwise inaccessible to drugs delivered by oral and parenteral routes.

• Bacteria can be engineered to have affinity for certain tumors.• Bacteria can be engineered to express proteins on their surface for therapeutic or

diagnostic intervention

40

Biotinylated-anti-Listeria

monoclonal IgG

bacteria

Biotinylated and rhodamine red

conjugated plasmid DNA encoding GFP

Streptavidin40-nm texas red or

FITC conjugated and streptavidin-coated

nanoparticle

200-nm-FITC conjugated and streptavidin-coated

nanoparticle

I. Bacteria enters the cells via induced

phagocytosis

II. Bacterial toxin causes endosomal compartments to

disintegrate

III. Therapeutic cargo separates from the bacteria and is delivered to the

nucleus

Nucleus

Microbots loaded with nano-particlescarrying therapeutic peptides, antibodies, small molecule drugs, nucleic acid therapeutics

bacteria

bacteria

bacteria

Functionalization Strategy

D. Akin, J. Sturgis, K. Reghab, K. Burkholder, S. Muhammad, A. Bhunia, J. Robinson, R. Bashir, Nature Nanotechnology, 2007

41

Nanoparticles on Bacteria

0

50

100

150

200

250

300

0 0.2 0.4 0.6

Distance (microns)

Gre

y Va

lue

RG

G

R

c d e

hgf

i j

42

Bacterial Mediated Delivery of NP

(d)(a)

1

10

100

1000

0.5hr 1hr 1.5hr 3hr

Incubation Time

Mea

n FL

(FIT

C) Mean FL (200nm)

Cells alone(a)

1

10

100

1000

0.5hr 1hr 1.5hr 3hr

Incubation Time

Mea

n FL

(FIT

C) Mean FL (200nm)

Cells alone

(e)

05

10152025303540

NP mBot

Part

icle

s/ce

ll

05

10152025303540(e)

05

10152025303540

NP mBot

Part

icle

s/ce

ll

05

10152025303540

(c)

(b)

43

Expression of GFP in KB CellsExpression in-vitro in cells Expression in-vitro in mice

D. Akin, J. Sturgis, K. Reghab, K. Burkholder, S. Muhammad, A. Bhunia, J. Robinson, R. Bashir, Nature Nanotechnology, 2007

A. Gupta, D. Akin, R. Bashir, Applied Physics Letters, 2004.A. Gupta, et al. Proc. Nat. Acad. Sci. 2006

Detection of Virus Particles

f0 = 1.27 MHzf1 = 1.21 MHz

Q ~ 5k = 0.006 N/m

∆f=60kHz

• Ultimate Sensitivity ~ 6.3 Hz/ag (in air)• Min. Detectable Mass (Q = 5, ∆f = 40kHz) ~ 6.3fg• Min. Detectable Mass (Q = 500, ∆f = 400Hz) ~ 50ag• Work on going to integrated concentration elements

Work featured in Popular Science, EE Times, Work featured in Popular Science, EE Times, Nature News, and CNBC TV ShowNature News, and CNBC TV Show

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Interfacing Biology and Engineering at the Micro and Nano Scale · 2017-01-26 · Interfacing Biology and Engineering at the Micro and Nano Scale March 8th, 2008 ... * Size information