Transcript Document

School of Biomedical Engineering, Science & Health Systems
NANOBIOSENSOR RESEARCH
The Challenges
• Attain a fundamental understanding of nanoscale biosensing phenomena.
• Design and fabricate biologically active sensing interfaces: DNA, proteins, cells, tissues, other.
• Design and fabricate solid-state based transducer structures capable of simultaneous detection of
multiple biological substances and processes: biosensor chips, biosensor arrays, other.
• Novel theoretical and experimental tools for a rapid development of the NanoBiosensor technology.
• Integration of biological, physical (mechanical, optical, acoustic) and electronic components into
multifunctional biosensor systems: novel immobilization techniques; solid-state transducer
nano/microfabrication technologies; microfluidic systems; IC circuits for signal conditioning and
processing; smart biosensors and biosensor systems.
30
-32.40
25
Amplitude in dB
Magnitude (dB)
Sedimentation
-32.45
Adhesion
-32.50
Spreading
-32.55
15
10
5
-32.60
-32.65
20
0
10
20
30
40
50
60
Time (min)
0
0
50
100
150
200
250
300
Time in Minutes
Sedimentation, adhesion, and proliferation of
endothelial cell proliferation
Deposition of super collagen on the gold surface in
0.1 mol of HCl solution
Spreading of Endothelial Cell
Faculty: Ryszard M. Lec, PhD, Drexel University.
E-mail: [email protected]
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NANOBIOSENSOR RESEARCH
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Development of Piezoelectric NanoBiosensor Technology
Platform
Important Features:
Piezoelectric Crystal
• Multidomain Piezoelectric Sensing Mechanisms: mass,
viscosity, elasticity, electric conductivity, and dielectric
constants.
100 MHz
• Real-time Piezoelectric Monitoring of Interfacial
Biological Phenomena: the depth of monitoring ranges
from a single to hundreds nanometers with the time resolution
of milliseconds.
Electrode
Cross Section
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1 GHz
10 MHz
• Piezoelectric Biotransducer Technology: IC compatible,
MEMS/NEMS; sensing and actuating; multiple-sensingwave transducers, piezo-bio-chips and arrays, other.
• Bio-Piezo-Interfaces: design and synthesis of surfaces at the
atomic level to produce sensing interfaces with desired
properties and functions.
Top View
• Integrated Electronic Signal Processing and Display
Technologies: fast, miniature, inexpensive, reliable.
Array Transducer Design
• Smart Biosensors: self-calibration, self-diagnostic,
self-repair, other.
PNBS
ASW
Frequency
Frequency
1 MHz
Penetration
Depth δ
10
100kHz
MHz
~10
μm
980 nm
GHz
11 MHz
~981nm
μm
Piezo-Bio-Array
Liquid
(H2O)
First
(Fundamental)
y
28 nm
100 MHz
~ 0.1 μm
PNBS
ASW
Penetration
Penetration Depth
Frequency
Frequency Depth δ37 nm
500 MHz
5 MHz
0.5 μm
Decay of Acoustic
Shear Wave
(Envelope)
x

u  x  u o exp(    y )  exp([ i ( t 
 y )]
Vx
 
1


2
,V x 

2 

Decay of Acoustic
Shear Wave
(Envelope)
Fifth
Seventh
.
Harmonic
Frequency
.
Displacement
Electrode
Excitation
Voltage
Piezoelectric Quartz
Electrode
Solid/Liquid Interface
(Boundary Conditions)
Third
Liquid
(H2O)
Air
Shear-Mode Piezo-Biosensor (Fundamental)
Excitation
Voltage
Piezoelectric Quartz
Air
Shear-Mode Piezo-Biosensor (Harmonics)
Faculty: Ryszard M. Lec, PhD, Drexel University.
E-mail: [email protected]
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School of Biomedical Engineering, Science & Health Systems
NANOBIOSENSOR RESEARCH
Novel Applications of Piezoelectric NanoBiosensor Technology
•
DNA sensors/chips: genetic screening and diseases, drug testing, environmental monitoring, biowarfare,
bioterrorism, other.
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Immunosensors: HIV, hepatitis, other viral diseases, drug testing, environmental monitoring, biowarfare,
bioterrorism, other.
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Cell-based sensors: functional sensors, drug testing, environmental monitoring, biowarfare, bioterrorism,
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other.
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Point-of-care sensors: blood, urine, electrolytes, gases, steroids, drugs, hormones, proteins, other.
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Bacteria sensors (E-coli, streptococcus, other): food industry, medicine, environmental, other.
•
Enzyme sensors: diabetics, drug testing, other.
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Market: clinical diagnostic, environmental monitoring, biotechnology, pharmaceutical industry, food
analysis, cosmetic industry, other.
– Immunosensors: about 1 billion annually.
– DNA probes: about 1.5 billion annually.
Portable Measurement System
Oscillator, Phase Lock Loop System
Vector
Voltmeter
System
Time
Domain
Analyzer
Impedance
Meter
Network Analyzer
0.00E+00
-1.00E+01
-2.00E+01
Signal
-3.00E+01
-4.00E+01
-5.00E+01
-6.00E+01
-7.00E+01
-8.00E+01
4.97E+06
4.98E+06
4.99E+06
5.00E+06
5.01E+065.02E+06
5.03E+06
5.04E+06
Generator
1.00E+02
8.00E+01
6.00E+01
4.00E+01
2.00E+01
0.00E+00
4.97E+06
4.98E+06
4.99E+06
5.00E+06
5.01E+06
5.02E+06
5.03E+06
5.04E+06
-2.00E+01
-4.00E+01
-6.00E+01
-8.00E+01
-1.00E+02
-1.20E+02
Magnitude Display Signal
Receiver
Phase Display
Data Acquisition
and Control
Signal Processing
Computer
Control
Liquid
Flow
System
- antibody
- antigen
Liquid Chamber
Liquid Chamber
Temperature
Measurement
Piezoelectric Crystal
Electronic
Compartment
Signal In
Signal Out
Measurement Cell
(T, RH,C0 2 , pH, etc.)
Integrated laboratory system for testing and calibration of
piezoelectric biosensors.
Faculty: Ryszard M. Lec, PhD, Drexel University.
E-mail: [email protected]
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A NOVEL PIEZOELECTRIC MICROARRAY BIOSENSOR:
LABORATORY-ON-A-CHIP
Piezoelectric Interfacial NanoBioSensor (PINBS) - I
Piezoelectric Interfacial NanoBioSensor (PINBS) technology offers a unique opportunity to develop a biochip
in which both sensing and actuating (mixing, flowing, etc. ) are implemented using the same technology
platform.
ASW
Frequency
Penetration
Depth δ
10 kHz
~10 μm
1 MHz
~ 1 μm
100 MHz
~ 0.1 μm
ASW
Frequency
5 MHz
Penetration
Depth δ
0.5 μm
Piezoelectric Crystal
Liquid
(H2O)
100 MHz
y
Cross Section
Decay of Acoustic
Shear Wave
(Envelope)
1

2


,V x 
2 

Vx
1 GHz
10 MHz
x
u  x  u o exp(    y )  exp([ i ( t 
 
Electrode
 y )]

Displacement
Electrode
Excitation
Voltage
Piezoelectric Quartz
Electrode
Solid/Liquid Interface
(Boundary Conditions)
Air
Fig. 1 - PINBS operating at the fundamental frequency
Top View
Array Transducer Design
Fig. 4 - A PINBS Biochip
First
(Fundamental)
Third
1000
Liquid
(H2O)
Decay of Acoustic
Shear Wave
(Envelope)
100
Fifth
10
Seventh
.
Harmonic
Frequency
.
Excitation
Voltage
Piezoelectric Quartz
1
Air
Fig. 2 - PINBS operating at the harmonic frequencies
1
10
100
Freq. (MHz)
1,000
Fig. 3 - Probing depth of the PNBS as a function
of frequency
Faculty: Ryszard M. Lec, PhD, Drexel University.
E-mail: [email protected]
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School of Biomedical Engineering, Science & Health Systems
NOVEL INTERFACES FOR PIEZOELECTRIC
INTERFACIAL NANOBIOSENSORS
Piezoelectric Interfacial NanoBioSensor (PINBS) - II
This research is focused for development of artificial nanofiber-based interfaces for cell-based functional
biosensors.
PLAGA Nanofiber-based Biosesnor Interface
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Endothelial Cell on PLAGA Nanofiber Interface( initial stage) and after 2 hours ( nicely spread).
The PINBS response
To the nanofiber loading.
Faculty: Ryszard M. Lec, PhD, Drexel University.
E-mail: [email protected]
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School of Biomedical Engineering, Science & Health Systems
PIEZOELECTRIC BIOSENSOR FOR MONITORING INTERACTION OF
A SINGLE PARTICLE & CELL WITH SOLID SURFACES:
ENDOTHELIAL CELL ON A GOLD SURFACE
Micro-nano Particle Size Distribution Sensor
The objective of this project is to develop a technique for measuring particle size and binding energy between a
particle (cell) and the solid interface.
High
Frequency
Excitation
Piezoelectric Sensor
Piezoelectric Sensor
k
r
Nano-Microparticle-Cell on
the surface of the sensor
Piezoelectric Sensor
Nano-Microparticle-Cell
m – mass
k – effective elasticity
representing interfacial
bonding energy
r – dissipative losses
Piezoelectric Sensor:
M – mass
k – elasticity
r – dissipative losses
Piezoelectric Sensor
R
Equivalent Electromechanical System
Amplitude
f
Reference Sensor
Response
Sensor Response
with a Nanoparticle
10.00000
Frequency (MHz)
10.10000
Faculty: Ryszard M. Lec, PhD, Drexel University.
E-mail: [email protected]
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School of Biomedical Engineering, Science & Health Systems
PINBS FOR MONITORING INTERFACIAL PROCESSES
INVOLVING CELLS AND VARIOUS SURFACES
Endothelial Cell Properties Such As Sedimentation, Adhesion,
Proliferation, and Fixation
Sedimentation, adhesion and proliferation
profile of endothelial cells as a function of time
measured using 25 MHz piezoelectric
resonant sensor.
Brass housing
O-ring
Solution
Piezoelectric
Plate
Electrode
Faculty: Ryszard M. Lec, PhD, Drexel University.
E-mail: [email protected]
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School of Biomedical Engineering, Science & Health Systems
MONITORING THE KINETICS OF THIN BIOLOGICAL
FILM FORMATION IN REAL TIME
Phase Transitions of Thin Biological Films
PNBS
Probing
Frequency Depth
10 MHz
178 nm
The purpose of this project is the
development of a sensitive technique
for measuring phase transitions of
thin biological films.
Decay of Acoustic y
Shear Wave
(Envelope)
x
Displacement
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Electrode
Excitation
Voltage
Piezoelectric Quartz
Electrode
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Solid/Liquid Interface
(Boundary Conditions)
Deposition of Collagen on the gold surface
(50ul of Collagen in 0.1mol of Hcl)
Frequency Response at Fundamental Frequency
10.015
Frequency in MHz
10.01
10.005
10
9.995
9.99
9.985
9.98
9.975
9.97
0
50
100
150
200
250
300
Time in Minutes
Deposition of Collagen on the gold surface
(50ul of Collagen in 0.1mol of Hcl)
Phase in Degree
Phase Variation at Fundamental Frequency
100
80
60
40
20
0
0
50
100
150
200
250
300
Time in Minutes
Faculty: Ryszard M. Lec, PhD, Drexel University.
E-mail: [email protected]
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