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Optical vs. Non-Optical
Sanja Hadzialic
April 16, 2010
• 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
What is a Biosensor?
“A device consisting of a biological recognition system
(bioreceptor) and a transducer.”
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
Biosensor Structure
Sanja Hadzialic
Sanja Hadzialic
Sensor Requirements – A Wish List
 Sensitive - single/few molecule detection
 Specific
 Multiplexing - more information, provide subtype
 Label-free
 Easy to use
 Cheap
 Portable
Sanja Hadzialic
Electrochemical Biosensors
• Electrodes: voltage, current,
impedance measurement
• FET (Field-Effect Transistor)
• Nanowire Arrays\NanoparticleBased Sensors
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
• All immunological steps can
be performed in drop
Sensitivities: 104 – 10-4 µmol/L
Depending on the analyte
Sanja Hadzialic
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
Electrochemical: Nanowires/Nanoparticles
nanowires or carbon
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
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
[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,
[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
Optical Biosensors
• Fluorescence, Luminescence,
Transmission, Scattering
• Surface Plasmon Resonance
• Interferometer
• Optical Waveguide
• Ring resonator
• Optical Fiber
• Photonic Crystals
Optical: Fluorescence
Either target molecules or
bioreckognition molecules are
labeled with with fluorescent
Extremely sensitive: down to
single molecule.
Laborious labeling process, may
also interfere with the function
of the biomolecule.
Sanja Hadzialic
Optical: Label-Free Sensors
Measures the refractive index
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
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
Sanja Hadzialic
Optical: Interferometer
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
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
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
Optical: Ring Resonators
10-4 – 10-7 RIU
Silicon-on-insulator ring resonator.
Polymer ring resonator
Glass ring resonator array
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.
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).
Optical: Photonic Crystals
Photonic crystal microcavity based biosensor
Photonic crystal waveguide based biosensor
Photonic crystal fiber based biosensor
1D photonic crystal resonators array for parallel
• 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
DL: 10-3 - 10-5 RIU
Sanja Hadzialic
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
• Benefit from a developing infrastructure (entertainment and
telecommunication technologies)
• Label-free detection capabilities
[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
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
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.
107-102 cells or CFU/ml
(CFU, Colony Forming Unit)
4x4 quartz crystal sensor array
Sanja Hadzialic
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
• 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
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
and 700 kHz
Seo JH, Brand O (2005) Novel high Qfactor resonant
microsensor platform for chemical
and biological applications
13. Transducers 05, Proceedings 247–
Burg TB, Manalis SR (2003)
Suspended microchannel
for biomolecular detection. Appl
Phys Lett 83:2698–2700
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
[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
Optical biosensors
• Sensitive, immune to EM interference, fast and benefit from a developing
• Luminescence/fluorrescence well established, need tagging of the analyte
• SPR, waveguides and FBG are relatively mature and even commercialized
• 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
I’m good with either
of those…
Thank you
for your attention!!