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Transcript
Optical vs. Non-Optical
Biosensors
Sanja Hadzialic
April 16, 2010
1
Outline
• What is a biosensor?
• Biosensor Components
• Motivation: Why do we need biosensors?
• Biosensor Types:
- Electrochemical
- Optical
- Mass-sensitive
(Thermal/Calorimetric, Scanning Probe, Magnetic, Massspectroscopy…)
•Summary & Conclusions
Sanja Hadzialic
2
What is a Biosensor?
“A device consisting of a biological recognition system
(bioreceptor) and a transducer.”
Bioreceptors:
antibodies, enzymes, proteins, nucleic acids, cells, tissue, or
whole organisms.
Transduction methods:
- optical (luminescence, absorption, SPR, etc.)
- electrochemical
- mass-sensitive (quartz crystal microbalance, SAW, etc.)
- magnetic, thermal, etc…
Sanja Hadzialic
3
Biosensor Structure
Sanja Hadzialic
4
Applications
Sanja Hadzialic
5
Sensor Requirements – A Wish List
 Sensitive - single/few molecule detection
 Specific
 Multiplexing - more information, provide subtype
information
 Label-free
 Easy to use
 Cheap
 Portable
Sanja Hadzialic
6
Electrochemical Biosensors
• Electrodes: voltage, current,
impedance measurement
• FET (Field-Effect Transistor)
• Nanowire Arrays\NanoparticleBased Sensors
7
Electrochemical: Electrodes
• Usually requires a reference electrode, a counter electrode and a sensing electrode
• Use predominantly enzymes due to their specific binding capabilities and
biocatalytic activity (commercialy available)
Screen-printed electrodes
• Low-cost fabrication and
mass production
• Screen-printing (thickfilm):
printing of various inks onto
planar ceramic or plastic
supports
• All immunological steps can
be performed in drop
Sensitivities: 104 – 10-4 µmol/L
Depending on the analyte
measured
Sanja Hadzialic
8
Electrochemical: FET
Control of the conductivity is
achieved by varying the
electric field potential,
relative to the source and
drain electrode, at a third
electrode, known as the gate
The metal gate electrode is
replaced by a biochemically
sensitive surface
Charge accumulation at the gate
 Conductance change
Preferred for weak-signal and/or high impedance applications
Problems related to enzyme immobilization
Sanja Hadzialic
9
Electrochemical: Nanowires/Nanoparticles
nanowires or carbon
nanotubes
Binding to the surface of these nano-objects alters their ability to conduct
The surface-to-volume ratio, increases drastically  Binding of molecules produces
larger effect
Incorporated into FET devices for biosensing purposes, such as the detection of pH,
protein and DNA binding, viral and cancer markers
Sanja Hadzialic
10
Summary: Electrochemical Sensors
• Good sensitivity
• Compatibility with modern microfabrication technologies (electrodes)
• Simple (use by semi-skilled operator)
• Cheap
• Small/Portable
• Easily interfaced
• Minimal power requirements
• Compatible with extension to array formats and integration with microfluidic
structures.
References:
[1] D. Grieshaber, R. MacKenzie, J. Voros, and E. Reimhult, "Electrochemical biosensors - Sensor principles and architectures," Sensors, vol. 8, pp.
1400-1458, 2008.
[2] F. Ricci, G. Volpe, L. Micheli, and G. Palleschi, "A review on novel developments and applications of immunosensors in food analysis,"
Analytica Chimica Acta, vol. 605, pp. 111-129, 2007.
[3] M. Tudorache and C. Bala, "Biosensors based on screen-printing technology, and their applications in environmental and food analysis,"
Analytical and Bioanalytical Chemistry, vol. 388, pp. 565-578, 2007.
[4] L. Murphy, "Biosensors and bioelectrochemistry," Current Opinion in Chemical Biology, vol. 10, pp. 177-184, 2006.
[5] J. S. Daniels and N. Pourmand, "Label-free impedance biosensors: Opportunities and challenges," Electroanalysis, vol. 19, pp. 1239-1257,
2007.
[6] F. Lucarelli, S. Tombelli, M. Minunni, G. Marrazza, and M. Mascini, "Electrochemical and piezoelectric DNA biosensors for hybridisation
detection," Analytica Chimica Acta, vol. 609, pp. 139-159, 2008.
Sanja Hadzialic
11
Optical Biosensors
• Fluorescence, Luminescence,
Transmission, Scattering
• Surface Plasmon Resonance
• Interferometer
• Optical Waveguide
• Ring resonator
• Optical Fiber
• Photonic Crystals
12
Optical: Fluorescence
Either target molecules or
bioreckognition molecules are
labeled with with fluorescent
tags.
Extremely sensitive: down to
single molecule.
Laborious labeling process, may
also interfere with the function
of the biomolecule.
Sanja Hadzialic
13
Optical: Label-Free Sensors
Measures the refractive index
change
Light concentrated near the
sensor surface
(decay length of a few tens to a
few hundreds of nm)
X. D. Fan, I. M. White, S. I. Shopoua, H. Y. Zhu, J. D. Suter, and Y. Z. Sun, "Sensitive optical biosensors for
unlabeled targets: A review," Analytica Chimica Acta, vol. 620, pp. 8-26, 2008.
Sanja Hadzialic
14
Optical: Surface Plasmon Resonance
(A) Prism coupling, (B) waveguide coupling, (C) optical fiber coupling, (D) side-polished fiber coupling, (E) grating coupling
and (F) long-range and short-range surface plasmon (LRSP and SRSP)
• SPW: charge density oscillation occuring at the interface of two media with dielectric
constants of opposite signs
• At the resonant angle or resonant wavelength, the propagation constant of the
evanescent field matches that of the SPW
• DL: 10-5-10-8 RIU
15
Sanja Hadzialic
Optical: Interferometer
v
Mach-Zehnder interferometer
•High loss at the input coupling interface
•DL of 10-7 RIU
Young’s interferometer
•Interference fringes on a
detector screen - FFT
•DL of 10-7 RIU
A change in the RI at the surface of the sensor arm results in an
optical phase change on the sensing arm
Sanja Hadzialic
16
Optical: Waveguide
Resonnant Mirror:
• Resonant angle
 the light can be coupled
strongly into the high-index
waveguide layer
strong reflection
• Sensitive to the RI change
• Supports both TE and TM
modes (different resonant
angles)
Sanja Hadzialic
Reverse Symmetry Waveguide:
• Porous silica cladding (low RI)  more light
concentrated near the sensing surface
Metal Clad Waveguide:
Symmetric Metal Clad Waveguide:
•DL of 2×10−7 RIU
17
Optical: Ring Resonators
(A)
(B)
(C)
(D)
(E)
(F)
10-4 – 10-7 RIU
Silicon-on-insulator ring resonator.
Polymer ring resonator
Microtoroid
Glass ring resonator array
Microsphere
Capillary-based opto-fluidic ring resonator
• Whispering gallery modes (WGMs)
or circulating waveguide modes.
• Evanescent field present at the ring
resonator surface responds to
the binding of biomolecules.
10-7 RIU
Effective length:
Sanja Hadzialic
10-6 – 10-7 RIU
Resonant wavelength:
• Sensing performance similar or
superior to a waveguide
• Orders of magnitude less surface
area and sample volume.
18
Optical: Fiber Based Biosensors
FBG (Fiber Bragg Grating): A band
rejection filter, reflecting a narrow
band of light at the Bragg
wavelength (~10-6 RIU).
LPG (Long Period Grating): core
modes couple into the cladding
modes (~10-4 RIU).
(A)D-shaped fiber with surface etched grating
(B)FBG on an etched fiber
(C) Nanofiber loop
(D)Fiber-optic coupler biosensor
(E) Fiber Fabry-Perot cavity DNA sensor showing hollow segment
(F) Fiber Fabry-Perot cavity
Sanja Hadzialic
Nanofiber: large evanescent field
 sensitive to RI change (~10-7 RIU)
Fabry-Perot resonator: spectral
reflectance sensitive to RI change
(~10-5 RIU).
19
Optical: Photonic Crystals
(A)
(B)
(C)
(D)
Photonic crystal microcavity based biosensor
Photonic crystal waveguide based biosensor
Photonic crystal fiber based biosensor
1D photonic crystal resonators array for parallel
detection
• Photonic bandgap structures
• A defect can be introduced by
disturbing the periodicity  sharp
peak within the bandgap (sensitive
to local RI change)
• Small sample volumes
• Cutoff wavelength of the PC waveguide was used as the indicator for RI changes
• Air holes in the PC fiber can act as a simple fluidic channel
• Narrowband wavelength reflectance filter with 100% reflectivity at the resonant
wavelength
DL: 10-3 - 10-5 RIU
Sanja Hadzialic
20
Summary: Optical Sensors
• Sensitive
• Fast
• Robust
• Suitable for miniaturization
• Can readily be multiplexed
• Immune to electromagnetic interference
• Free path or remote interrogation without the need for wire
connections
• Benefit from a developing infrastructure (entertainment and
telecommunication technologies)
• Label-free detection capabilities
References:
[1] X. D. Fan, I. M. White, S. I. Shopoua, H. Y. Zhu, J. D. Suter, and Y. Z. Sun, "Sensitive optical biosensors for unlabeled targets: A review," Analytica Chimica Acta, vol. 620,
pp. 8-26, 2008.
[2] D. Erickson, S. Mandal, A. H. J. Yang, and B. Cordovez, "Nanobiosensors: optofluidic, electrical and mechanical approaches to biomolecular detection at the nanoscale,"
Microfluidics and Nanofluidics, vol. 4, pp. 33-52, 2008.
[3] J. N. Anker, W. P. Hall, O. Lyandres, N. C. Shah, J. Zhao, and R. P. Van Duyne, "Biosensing with plasmonic nanosensors," Nature Materials, vol. 7, pp. 442-453, 2008.
[4] M. A. Cooper, "Optical biosensors: where next and how soon?," Drug Discovery Today, vol. 11, pp. 1061-1067, 2006.
[5] A. Leung, P. M. Shankar, and R. Mutharasan, "A review of fiber-optic biosensors," Sensors and Actuators B-Chemical, vol. 125, pp. 688-703, 2007.
[6] K. E. Sapsford, T. Pons, I. L. Medintz, and H. Mattoussi, "Biosensing with luminescent semiconductor quantum dots," Sensors, vol. 6, pp. 925-953, 2006.
Sanja Hadzialic
21
Mass-sensitive Biosensors
• Quartz Crystal Microbalance
• Surface Acoustic Waves
• Cantilevers
Convert a mass accumulated on the
surface into a frequency shift
Non-gravimetric effects:
• Energy dissipation at the surface
• Viscous damping
22
Mass-sensitive: Quartz Crystal Microbalance
The additional bound material lowers the
resonance frequency, which is transformed
into an electrical signal due to the
piezoelectric effect.
Sensitivity:
107-102 cells or CFU/ml
(CFU, Colony Forming Unit)
4x4 quartz crystal sensor array
Sanja Hadzialic
23
Mass-sensitive: Surface Acoustic Waves
The elements of the SAW biosensor are:
(2) A piezoelectric crystal
(3) IDTs (Inter-digitized transducers)
(4) The surface acoustic wave
(5) Immobilized antibodies
(7) The driving electronics
• Simple electronic setup
• Cheap component and electronic
interface
• May eventually be able to compete
with SPR
Sanja Hadzialic
• Surface acoustic wave (SAW) devices
• Surface transverse wave (STW) devices
• Flexural plate wave (FPW) devices
• Love wave (LW) devices
• Shear horizontal acoustic plate mode
(SH-APM)
24
Mass-sensitive: Cantilevers
• Commercial cantilevers are usually used
• Typically made of silicon, silicon nitride, or silicon dioxide
• Can be used in the resonant or non-resonant mode (stress-generated bending)
To avoid viscous damping in resonnant mode
Mass deposited on to the
cantilever  reduction of its
resonant frequency
Stress due to attachment of the
analyte  cantilever bending
Sanja Hadzialic
A disc-shaped
microstructure operates in
a rotational in-plane mode
with resonance
Cantilever with buried
frequencies between 300
microchannels
and 700 kHz
Seo JH, Brand O (2005) Novel high Qfactor resonant
microsensor platform for chemical
and biological applications
13. Transducers 05, Proceedings 247–
251
Burg TB, Manalis SR (2003)
Suspended microchannel
resonators
for biomolecular detection. Appl
Phys Lett 83:2698–2700
25
Summary: Mass-Sensitive Sensors
• Label-free detection capabilities
• Real-time data of binding events
• Sensitivity lower than SPR
• Limits of detection achieved typically lower than classical methods
(micro-cantilevers)
References:
[1] R. Lucklum and P. Hauptmann, "Acoustic microsensors-the challenge behind microgravimetry," Analytical and Bioanalytical Chemistry, vol.
384, pp. 667-682, 2006.
[2] M. A. Cooper and V. T. Singleton, "A survey of the 2001 to 2005 quartz crystal microbalance biosensor literature: applications of acoustic
physics to the analysis of biomolecular interactions," Journal of Molecular Recognition, vol. 20, pp. 154-184, 2007.
[3] K. Lange, B. E. Rapp, and M. Rapp, "Surface acoustic wave biosensors: a review," Analytical and Bioanalytical Chemistry, vol. 391, pp. 15091519, 2008.
Sanja Hadzialic
26
Conclusions
Optical biosensors
• Sensitive, immune to EM interference, fast and benefit from a developing
infrastructure.
• Luminescence/fluorrescence well established, need tagging of the analyte
molecules
• SPR, waveguides and FBG are relatively mature and even commercialized
technologies
• Ring resonators and PCs posses unique and advantageous properties.
Electrochemical biosensors
• Cheap and simple
• Glucose sensor has been a big commercial success
• Require development of catalytic enzymes
• Nanoelectrodes/nanotechnology to improve sensitivity
Mass-sensitive biosensors
• Cheap and simple components – both sensor and interface
• Not as sensitive as optical sensors
• Nano-materials might improve the sensitivity
Sanja Hadzialic
27
I’m good with either
of those…
28
(
Thank you
for your attention!!
29