Ivan Rech Politecnico di Milano MICROELECTRONIC PHOTOSENSORS FOR GENETIC DIAGNOSTIC MICROSYSTEMS GE...
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Transcript of Ivan Rech Politecnico di Milano MICROELECTRONIC PHOTOSENSORS FOR GENETIC DIAGNOSTIC MICROSYSTEMS GE...
Ivan RechPolitecnico di Milano
MICROELECTRONIC PHOTOSENSORS FOR GENETIC DIAGNOSTIC MICROSYSTEMS GE 2003 , June 13, 2003
MICROELECTRONIC PHOTOSENSORS MICROELECTRONIC PHOTOSENSORS
FOR GENETIC DIAGNOSTIC MICROSYSTEMSFOR GENETIC DIAGNOSTIC MICROSYSTEMS
MICROELECTRONIC PHOTOSENSORS MICROELECTRONIC PHOTOSENSORS
FOR GENETIC DIAGNOSTIC MICROSYSTEMSFOR GENETIC DIAGNOSTIC MICROSYSTEMS
GE 2003
I. Rech; S. Cova; F. Zappa; M. GhioniPolitecnico di Milano - DEI, piazza. Leonardo da Vinci 32, 20133 Milano, Italy
M. Chiari; M. Cretich
CNR - ICRM, via M. Bianco, 20133 Milano
Ivan RechPolitecnico di Milano
MICROELECTRONIC PHOTOSENSORS FOR GENETIC DIAGNOSTIC MICROSYSTEMS GE 2003 , June 13, 2003
Outline
• Analytical Microsystems and Fluorescence Detection
• SPAD detectors
• Experimental set-up
• Results and prospect
Ivan RechPolitecnico di Milano
MICROELECTRONIC PHOTOSENSORS FOR GENETIC DIAGNOSTIC MICROSYSTEMS GE 2003 , June 13, 2003
Goal : reduced measurement
operation costs
• higher performance
• lower cost
• higher flexibility
• better automation and control
Genetical analysis
Analisys set-upRequirements :
Small volumes of the reagents
Ivan RechPolitecnico di Milano
MICROELECTRONIC PHOTOSENSORS FOR GENETIC DIAGNOSTIC MICROSYSTEMS GE 2003 , June 13, 2003
Requirements to Detector
• high QE (Quantum detection Efficiency)
• Low internal noise
• High sensitivity down to Single-Photon detection
• PMT, Photomultiplier Tubes
• CCD, Charge-Coupled Devices
• APD, Avalanche PhotoDiodes
• SPAD, Single-Photon Avalanche Diodes
High-Sensitivity Detectors
Ivan RechPolitecnico di Milano
MICROELECTRONIC PHOTOSENSORS FOR GENETIC DIAGNOSTIC MICROSYSTEMS GE 2003 , June 13, 2003
• Bias: well ABOVE breakdown
• Geiger-mode: it’s a TRIGGER device!!
• Gain: meaningless ... or “infinite” !!
• Bias: slightly BELOW breakdown
• Linear-mode: it’s an AMPLIFIER
• Gain: limited < 1000
Avalanche PhotoDiode Single-Photon Avalanche Diode
APD SPAD
Ivan RechPolitecnico di Milano
MICROELECTRONIC PHOTOSENSORS FOR GENETIC DIAGNOSTIC MICROSYSTEMS GE 2003 , June 13, 2003
• Well defined high-field region
• No edge effects
• No microplasmas
• Low generation rate
• Minimum afterpulsing effect
• Low series resistance
• Low cost process
• Low Power dissipation
n
p++p
p
hv
+n
anode cathode
Planar SPAD structure
Ivan RechPolitecnico di Milano
MICROELECTRONIC PHOTOSENSORS FOR GENETIC DIAGNOSTIC MICROSYSTEMS GE 2003 , June 13, 2003
High QE (Quantum detection Efficiency)
Ivan RechPolitecnico di Milano
MICROELECTRONIC PHOTOSENSORS FOR GENETIC DIAGNOSTIC MICROSYSTEMS GE 2003 , June 13, 2003
0
5
10
15
20
25
30
35
40
0 1 2 3 4 5 6 7 8 9 10 11 12 13
Sovratensione (V)
Cont
eggi
di B
uio
(cou
nts/
sec.
)
100
150
200
250
300
350
400
0 1 2 3 4 5 6 7 8 9 10 11 12 13
Sovratensione (V)Co
nteg
gi d
i Bui
o (c
ount
s/se
c.)
Active area diameter : 10 Active area diameter : 10 mm Active area diameter : 20 Active area diameter : 20 mm
Low internal noise : Dark Counts
Ivan RechPolitecnico di Milano
MICROELECTRONIC PHOTOSENSORS FOR GENETIC DIAGNOSTIC MICROSYSTEMS GE 2003 , June 13, 2003
Dark Counts Vs Temperature
0
50
100
150
200
250
300
350
-30 -20 -10 0 10 20
Temperature [C°]
Da
rk C
ou
nts
[c
/s]
+5V
+10V
0
50
100
150
200
250
300
350
-30 -20 -10 0 10 20
Temperature [C°]
Da
rk C
ou
nts
[c
/s]
+5V
+10V
Experimental set-up
Ivan RechPolitecnico di Milano
MICROELECTRONIC PHOTOSENSORS FOR GENETIC DIAGNOSTIC MICROSYSTEMS GE 2003 , June 13, 2003
Fragment separation
Electropherogram
Ivan RechPolitecnico di Milano
MICROELECTRONIC PHOTOSENSORS FOR GENETIC DIAGNOSTIC MICROSYSTEMS GE 2003 , June 13, 2003
Counting Module
• Single power supply +5V• Software controlled settings• RS-232 data transmission• Fmax 6.5 MHz• Waveform storage
Politecnico di Milano
MICROELECTRONIC PHOTOSENSORS FOR GENETIC DIAGNOSTIC MICROSYSTEMS GE 2003 , June 13, 2003
Ivan RechPolitecnico di Milano
MICROELECTRONIC PHOTOSENSORS FOR GENETIC DIAGNOSTIC MICROSYSTEMS GE 2003 , June 13, 2003
SeparationInjection
Sample
Buffer
Waste
Chip Electrophoresis
Ivan RechPolitecnico di Milano
MICROELECTRONIC PHOTOSENSORS FOR GENETIC DIAGNOSTIC MICROSYSTEMS GE 2003 , June 13, 2003
First Experimental Setup
Ivan RechPolitecnico di Milano
MICROELECTRONIC PHOTOSENSORS FOR GENETIC DIAGNOSTIC MICROSYSTEMS GE 2003 , June 13, 2003
Ivan RechPolitecnico di Milano
MICROELECTRONIC PHOTOSENSORS FOR GENETIC DIAGNOSTIC MICROSYSTEMS GE 2003 , June 13, 2003
Current Apparatus : SV3
• Compact and low-cost
• Full automated
• Laser diode for fluorescence excitation
• Controlled chip temperature
• Dual wavelength electropherogram
• Dual HV power supply (0-5kV)
• Confocal optical scheme
• Remote control and problem debug
(via internet)
Ivan RechPolitecnico di Milano
MICROELECTRONIC PHOTOSENSORS FOR GENETIC DIAGNOSTIC MICROSYSTEMS GE 2003 , June 13, 2003
Results
Ivan RechPolitecnico di Milano
MICROELECTRONIC PHOTOSENSORS FOR GENETIC DIAGNOSTIC MICROSYSTEMS GE 2003 , June 13, 2003
121416181101121141161181
0
10000
20000
30000
40000
50000
60000
70000
80000
Static measure5ng/ul
0,5ng/ul
0,05ng/ul
100pM oligonucleotide labelled with CY 5
300
400
500
600
700
800
900
1000
1100
1200
1300
0 50 100 150 200Time [Sec.]
Co
un
ts [
c/s]
S/N=35
• Glass microchips purchased from Micralyne Inc. (Edmonton, Canada).• Electrosmotic flow in the separation channels suppressed by EPDMA • dynamic coating . • Separation run buffer: TAPS-TRIS 100mM pH 8.5.• Sample :23 mer oligonucleotide labelled with CY 5
• Detection limitDetection limit ( with S/N=3) :( with S/N=3) : 3pM3pM (with injection volume 50pL)
Ivan RechPolitecnico di Milano
MICROELECTRONIC PHOTOSENSORS FOR GENETIC DIAGNOSTIC MICROSYSTEMS GE 2003 , June 13, 2003
SPTM- Single Photon Timing Module
• Single power supply +15V• High Time-resolution (60ps) • Low dark Counts (down to 5 c/sec)• Controlled Temperature
• Software controlled settings• RS-232 data transmission
Politecnico di Milano
Single Molecole Detection Collaboration with S.XieHarvard Univ. Dept. Chemistry and Chemical Biology
FWHM=60ps
MICROELECTRONIC PHOTOSENSORS FOR GENETIC DIAGNOSTIC MICROSYSTEMS GE 2003 , June 13, 2003
Ivan RechPolitecnico di Milano
MICROELECTRONIC PHOTOSENSORS FOR GENETIC DIAGNOSTIC MICROSYSTEMS GE 2003 , June 13, 2003
Prospect
Ivan RechPolitecnico di Milano
MICROELECTRONIC PHOTOSENSORS FOR GENETIC DIAGNOSTIC MICROSYSTEMS GE 2003 , June 13, 2003
• Improved optics sensitivity enhancement to 100fM
• Wider-area SPAD simpler set-up
• monolithic SPAD&AQC micro-miniaturized detection head
• SPAD arrays elaborate detection head
Prospect
Ivan RechPolitecnico di Milano
MICROELECTRONIC PHOTOSENSORS FOR GENETIC DIAGNOSTIC MICROSYSTEMS GE 2003 , June 13, 2003
Acknowledgments
Politecnico di Milano, Italy
Alessandro Restelli Electronics & Optics
Ivan Labanca
Dario Vagni
Giuseppe Liaci
Fabrizio Mingozzi ICRM-CNR, Milano, Italy:
Marcella CHIARI Polymers & Electrophoresis
Marina CRETICH
CEQSE-CNR, Milano, Italy:
Luciano PALLARO Mechanics & Optics
Ivan RechPolitecnico di Milano
MICROELECTRONIC PHOTOSENSORS FOR GENETIC DIAGNOSTIC MICROSYSTEMS GE 2003 , June 13, 2003
Thin SPAD’s Thick SPAD’s
• Good QE and low noise
• Picosecond timing
• Low voltage : 15 to 40V
• Low power : cooling not necessary
• Standard Si substrate
• Planar fabrication process
(compatible with IC integrated circuits)
• Robust and rugged
• Low-cost
• NO COMMERCIAL SOURCE TODAY
• Very good QE and low noise
• Sub-nanosecond timing
• High voltage : 300 to 400V
• High dissipation : Peltier cooler required
• Ultra-pure high-resistivity Si substrate
• Dedicated fabrication process
(NOT compatible with IC’s)
• Delicate and degradable
• Expensive
• SINGLE COMMERCIAL SOURCE