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School of Biomedical Engineering, Science and Health Systems
Ryszard Lec
Professor of Biomedical
& Electrical Engineering
Biosensors
Initiative Collage
Drexel University
Philadelphia, PA
V 1.0 [MS010517]
www.biomed.drexel.edu
School of Biomedical Engineering, Science and Health Systems
Nano-Biosensor Science, Engineering
and Technology: The Challenges
• Attain a fundamental understanding of nanoscale
biosensing phenomena.
• Design and fabricate biologically active sensing
interfaces: DNA, proteins, cells, tissues, other.
Endothelial Cell Proliferation
• Design and fabricate solid-state based transducer
structures capable of simultaneous detection of multiple
biological substances and processes: biosensor chips,
biosensor arrays, other.
Sedimentation
Adhesion
Proliferation
• Novel theoretical and experimental tools for a rapid
development of the Nano-Biosensor technology.
Sedimentation, adhesion, and proliferation
of Endothelial Cell Proliferation
30
Amplitude in dB
25
20
15
10
5
0
0
50
100
150
200
250
Time in Minutes
Deposition of super collagen on the gold
surface in 0.1 mol of HCl solution
V 1.0 [MS010517]
300
• 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.
School of Biomedical Engineering, Science and Health Systems
ASW
PNBS
Frequency
Frequency
Penetration
Depth δ
10 kHz
1 MHz
1 MHz
100 MHz
100 MHz
1 GHz
~10 μm
980 nm
~ 1 μm
98 nm
~ 0.1 μm
28 nm
ASW
Penetration
PNBS
Penetration
Frequency
FrequencyDepth δDepth
5 MHz
0.5 μm
37 nm
500 MHz
Liquid
(H2O)
y
Decay of Acoustic
Shear Wave
(Envelope)
x
u  x  u o exp(    y )  exp([ i ( t 
 
1

2
,V x 


2 

Vx
 y )]

Displacement
Electrode
Excitation
Voltage
Piezoelectric Quartz
Electrode
Solid/Liquid Interface
(Boundary Conditions)
Air
Shear-Mode Piezo-Biosensor (Fundamental)
First
(Fundamental)
Third
Liquid
(H2O)
Decay of Acoustic
Shear Wave
(Envelope)
Fifth
Seventh
.
Harmonic
Frequency
.
Excitation
Voltage
Piezoelectric Quartz
Air
Shear-Mode Piezo-Biosensor (Harmonics)
Piezoelectric Crystal
100 MHz
Electrode
Cross Section
1 GHz
10 MHz
Top View
Nano-Biosensor Science, Engineering and Technology
Objective: Development of Piezoelectric Nano-Biosensor
Technology Platform
Important Features:
• Multidomain Piezoelectric Sensing Mechanisms: mass,
viscosity, elasticity, electric conductivity, and dielectric
constants.
• 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.
• 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.
• Integrated Electronic Signal Processing and Display
Technologies: fast, miniature, inexpensive, reliable.
Array Transducer Design
Piezo-Bio-Array
V 1.0 [MS010517]
• Smart Biosensors: self-calibration, self-diagnostic,
self-repair, other.
School of Biomedical Engineering, Science and Health Systems
Nano-Biosensor Science, Engineering and Technology
Objective: Novel Applications of Piezoelectric Nano-Biosensor Technology
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+06
5.02E+06
5.03E+06
5.04E+06
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
Generator
Magnitude DisplaySignal
Receiver
Phase Display
Data Acquisition
and Control
SignalProcessing
Computer
Control
Liquid
Flow
System
antigen
Electronic
Compartment
Signal Out
Measurement Cell
(T, RH,C0
2 , pH, etc.)
Integrated Laboratory System for Testing
and Calibration of Piezoelectric Biosensors
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• Cell-based sensors: functional sensors, drug testing,
environmental monitoring, biowarfare, bioterrorism, other.
• Point-of-care sensors: blood, urine, electrolytes, gases, steroids,
drugs, hormones, proteins, other.
• Bacteria sensors (E-coli, streptococcus, other): food industry,
medicine, environmental, other.
• Enzyme sensors: diabetics, drug testing, other.
Piezoelectric Crystal
Signal In
• Immunosensors: HIV, hepatitis, other viral diseases, drug
testing, environmental monitoring, biowarfare, bioterrorism, other.
- antibody
Liquid Chamber
Liquid Chamber
Temperature
Measurement
• DNA sensors/chips: genetic screening and diseases, drug testing,
environmental monitoring, biowarfare, bioterrorism, other.
• 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
School of Biomedical Engineering, Science and Health Systems
Nano-Biosensor Research Laboratory
Project Title: Sensing Principles of Piezoelectric Nano-Biochemical Sensors (PNBS)
Michael Francois (Ph.D), Sun Jong Kwoun (MS Student)
Advisors: Dr. Ryszard M. Lec, Dr. Kambiz Pourrezaei
ASW
PNBS
Frequency
Frequency
Penetration
Depth δ
10 kHz
1 MHz
~10 μm
Liquid
(H2O)
980 nm
98 nm
100 MHz
1 GHz
28 nm
~ 0.1 μm
x
u  x  u o exp(    y )  exp([ i ( t 
0.5 μm
5 MHz
First
(Fundamental)
Decay of Acoustic
Shear Wave
(Envelope)
PNBS
ASW
Penetration
Frequency Depth δ
Frequency
500 MHz
Liquid
(H2O)
y
~ 1 μm
1 MHz
100 MHz
37 nm
 
1


2
,V x 

2 

Vx
Third
 y )]
Decay of Acoustic
Shear Wave
(Envelope)
Fifth

Seventh
Displacement
.
Harmonic
Frequency
.
Electrode
Excitation
Voltage
Piezoelectric Quartz
Electrode
Solid/Liquid Interface
(Boundary Conditions)
Excitation
Voltage
Piezoelectric Quartz
Air
Air
Fig. 1. PNBS operating at the fundamental frequency
Fig. 2. PNBS operating at the harmonic frequencies
Piezoelectric Crystal
1000
100 MHz
10 MHz
Electrode
Cross Section
1 GHz
100
Penetration
Depth
[nanometers]
10
1
1
10
100
Freq. (MHz)
1,000
10,000
Top View
Array Transducer Design
V 1.0 [MS010517]
Fig. 3. Probing depth of the PNBS as a function of frequency
Fig. 4. A PNBS Biochip
School of Biomedical Engineering, Science and Health Systems
Nano-Biosensor Research Laboratory
Project Title: A Novel Polymer Nanofiber Interface
for Biochemical Sensor Applications
Sun Jong Kwoun (MS Student)
Advisors: Dr. Ryszard M. Lec (Biomed.), Dr. Frank K. Ko (Material Eng. Dept.)
Fig. 1. Photograph of the TSM sensor
with deposited nanofiber film.
Fig. 2. SEM picture of the nanofiber
film at 6000X magnifications.
Fig. 3. Endothelial cell attached
to the nanofiber matrix.
NF Sensor
Fig. 3. Cell growth on nano fibrous matrix (after 1 day).
V 1.0 [MS010517]
Air
Fig. 4. The S21 amplitude of the nanofiber deposited sensors
in air as a function of frequency for five different deposition
time (corresponding to different NF film thickness).
School of Biomedical Engineering, Science and Health Systems
Nano-Biosensor Research Laboratory
Project Title: Piezoelectric Biosensor for Monitoring the Interaction of
a single cell with solid surfaces: Endothelial Cell on Gold Surface
Qiliang Zhang (Ph.D student)
Advisors: Dr. Ryszard M. Lec (Biomed), Dr. Kambiz Pourrezaei (ECE)
Nano-Microparticle-Cell
on the surface of the sensor
High
Frequency
Excitation
Piezoelectric Sensor
r
Nano-Microparticle-Cell on
the surface of the sensor
k
Piezoelectric Sensor
Nano-Microparticle-Cell
m – mass
k – effective elasticity
representing interfacial
bonding energy
r – dissipative losses
Piezoelectric Sensor
Amplitude
f
Sensor Response with a
Nanoparticle
Piezoelectric Sensor
R
Piezoelectric Sensor:
M – mass
k – elasticity
r – dissipative losses
10.00000
Equivalent Electromechanical Circuit
V 1.0 [MS010517]
Reference Sensor Response
Frequency (MHz)
10.10000
School of Biomedical Engineering, Science and Health Systems
Nano-Biosensor Research Laboratory
Project Title: Piezoelectric Nano-Biosensor for Monitoring Interfacial Cell Processes:
Endothelial Cell Properties such as sedimentation, adhesion, proliferation and fixation
Students: Vadivel Devaraju, (PhD) and Joe Sorial, (MS)
Faculty: Dr. Ryszard M. Lec and Dr. Kenneth Barbee
Brass housing
O-ring
Solution
Piezoelectric
Plate
Electrode
Fixation
Sedimentation
5MHz
Attachment
Proliferation
15MHz
Fixation
Figure 1. (a) Sedimentation, adhesion and proliferation profile of endothelial cells as a function of time measured
V 1.0 [MS010517]
using 25 MHz piezoelectric resonant sensor + the caption for the second picture
School of Biomedical Engineering, Science and Health Systems
Nano-Biosensor Research Laboratory
Project Title: Piezoelectric Nano-Biosensor for Monitoring Interfacial Protein Processes
Student: Vadivel Devaraju, (PhD)
Faculty: Dr. Ryszard M. Lec and Dr. Andrew Fertala
Probing
Depth
178 nm
Decay of Acoustic
Shear Wave
(Envelope)
y
Frequency Response at Fundamental Frequency
x
Displacement
Frequency in MHz
PNBS
Frequency
10 MHz
Deposition of Collagen on the gold surface
(50ul of Collagen in 0.1mol of Hcl)
Electrode
Excitation
Voltage
Piezoelectric Quartz
Electrode
Solid/Liquid Interface
(Boundary Conditions)
10.015
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)
Deposition of Collagen on the gold surface
(50ul of Collagen in 0.1mol of Hcl)
Phase Variation at Fundamental Frequency
30
20
10
0
0
50
100
150
Time in Minutes
V 1.0 [MS010517]
200
250
300
Phase in Degree
Amplitude in
dB
Amplitude Changes at Fundamental Frequency
100
80
60
40
20
0
0
50
100
150
Time in Minutes
200
250
300
School of Biomedical Engineering, Science and Health Systems
School of Biomedical Engineering,
Science & Health Systems
WWW.BIOMED.DREXEL.EDU
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V 1.0 [MS010517]