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(i) Bio recognition element to detect biological species.
(ii) Transduction mechanism which converts the physical or chemical
response into an optical signal.
(i) A light source
(ii) An optical transmission medium (fiber, waveguide, etc.)
(iii) Immobilized biological recognition element (enzymes,
antibodies or microbes)
(iv) Optical probes (such as a fluorescent marker) for
transduction
(v) An optical detection system.
o Nanoparticles play a significant role in various fields such as biomedical
imaging and diagnostics.
o Nano-sized biological agents , such as viruses are known to be responsible for a
wide variety of human diseases such as flu, AIDS and herpes, and have been
used as bio warfare agents.
o Accurate quantification of the presence of human viruses such as HIV, herpes or
influenza in blood samples is essential for clinical diagnosis and also for vaccine
development.
o The ability to distinguish between different kinds of viruses present in a sample is
also highly desirable.
o For example, a single patient may be confected with multiple viral pathogens
such as HIV and HCV, and being able to identify and quantify both viruses is
crucial for the patient to be treated appropriately.
o Optical methods have proved particularly attractive because of their non
aggressive nature and high sensitivity.
o Optical techniques based on sensing discrete resonance shifts in whispering
gallery mode (WGM) , micro cavities due to binding of single virus particles
have proved really promising, but they cannot be used to distinguish between
viruses of different sizes present in a heterogeneous mixture.
o Other optical sensing platforms such as those based on nanoplasmonics or
interferometry have proved to be sensitive to single viruses; but while some of
them need to be run for a long time and hence are unsuitable for real-time
sample characterization, others rely on extensive surface preparation steps or
availability of specific antibodies for the target viruses in a sample.
o Optical detection of nanoscale biological agents (such as viruses) using light
scattering is difficult due to their low scattering cross-section and low index
contrast to the surrounding medium.
o Nanomaterials used : mixtures of gold and polystyrene particles of different sizes.
o The particle size distributions recorded for a mixture of polystyrene particles with
mean radii of 50 nm and 75 nm, using the heterodyne (red) and homodyne (green)
signals.
o Using heterodyne detection, one can clearly resolve the two particle sizes, with very
little overlap.
o On the other hand, the individual particle distributions are wider in the homodyne
case, and hence the distributions partly overlap.
o This illustrates the superior size resolution obtainable with heterodyne detection for a
heterogeneous mixture of particles.
o That heterodyne interferometry can be used very effectively to detect single
nanoparticles in solution with high sensitivity and selectivity.
o The possibilities of detecting and distinguishing between viruses in solution using
heterodyne interferometry.
o It is difficult to detect nanoscale biological particles such as single viruses in
solution using scattering based techniques.
o Due to their weak refractive index contrast with the suspending medium but
heterodyne detection helps overcome this difficulty.
o Using the heterodyne detection technique, we could successfully detect HIV,
Influenza, Sindbis, Vaccinia, Parainfluenza(Sendai), and Baculovirus in separate
samples on the single virus level.
o The size of most human viruses is in the range of 20−200 nm.
o The size distribution recorded for a sample of HIV virus for calibration purposes, the
mean radius of HIV particles is taken to be 50 nm, as determined from TEM
measurements .
o The size distribution for a sample of Sindbis virus. For calibration purposes, the
mean radius of Sindbis virus particles is assumed to be 35 nm according to TEM
measurements.
o To demonstrate the ability to distinguish between HIV and Sindbis viruses in
solution, the size distribution for a mixture of the two viruses is recorded .
o The two virus types can be resolved.
o The results indicate that it is possible to distinguish by size individual viruses in a
mixture of different virus types, provided we know, for calibration purposes, the
mean size of at least one virus type.
o A nozzle continuously delivers viral or synthetic
nanoparticles onto a toroidal-shaped microlaser, which
translates changes in polarizability into changes in
frequency splitting.
o The pump light and the split lasing modes are separated
using a wavelength division multiplexer (WDM).
o Split lasing modes are mixed in a photodetector (PD)
leading to a heterodyne beat note signal.
o Inset: Experimentally observed green ring due to up-
conversion of Er3+ ions traces the WGM along the
periphery of the micro resonator.
Before the arrival of nanoparticles, there is a single
laser mode with constant laser intensity
(i). With the arrival of the first nanoparticle, laser
mode splits into two ,leading to a beat note whose
frequency corresponds to the frequency splitting
(ii). Subsequent particle binding event changes the
beat frequency
(iii). Since the split lasing modes reside in the same
micro laser, environmental noise such as
temperature fluctuations (illustrated by a heat source
placed under the chip) affects both modes in the
same way leading to a self-referencing scheme
(iv). Thus, although each split mode undergoes
spectral shift, the splitting between them does not
change, making this detection scheme resistant to
environmental noises .
The researchers attached red, green or orange
nanoparticles to antibodies that specifically
bind to proteins from the organisms that cause
Ebola, dengue or yellow fever, respectively.
Silver nanoparticles are employed and the sizes of
the nanoparticles determine their colors.
- : Chunwan Yen
Hamad-Schifferli and her team at the Massachusetts
Institute of Technology, Harvard Medical School and the
U.S. Food and Drug Administration
• Selectivity and specificity
• Remote sensing
• Isolation from electromagnetic interference
• Fast, real-time measurements
• Multiple channels/multi parameters detection
• Compact design
• Real-time Optical Detection of Single Nanoparticles and Viruses using Heterodyne Interferometry
Anirban Mitra1 and Lukas Novotny1,2 Adapted from: Anirban Mitra and Lukas Novotny,“Real-time
optical detection of single nanoparticles and viruses using heterodyne interferometry,” Nano-
Optics for Enhancing Light-Matter Interactions on a Molecular Scale, B. Di Bartolo et al. (eds.),
Chapter 1, p.3–23, NATO Science for Peace and Security Series B: Physics and Biophysics (Springer,
Dordrecht, 2013). 1. Department of Physics and Astronomy, University of Rochester, Rochester NY
14627 2. Institute of Optics, University of Rochester, Rochester, NY 14627
https://www.photonics.ethz.ch/fileadmin/user_upload/pdf/Papers/mitra12d.pdf
• Detecting single viruses and nanoparticles using whispering gallery microlasers Lina He, Sahin Kaya
Ozdemir, Jiangang Zhu, Woosung Kim, Lan Yang* Department of Electrical and Systems
Engineering, Washington University in St. Louis, MO 63130, USA * yang@ese.wustl.edu
http://arxiv.org/ftp/arxiv/papers/1107/1107.0868.pdf
• Optical Detection of Single Nanoparticles and Viruses Filipp V. Ignatovich, David Topham, and
Lukas Novotny
https://www.photonics.ethz.ch/fileadmin/user_upload/pdf/Papers/ignatovitch06b.pdf
http://www.acs.org/

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NANOPARTICLES USED IN OPTICAL DETECTION MODE FOR BIOSENSORS

  • 1.
  • 2. (i) Bio recognition element to detect biological species. (ii) Transduction mechanism which converts the physical or chemical response into an optical signal.
  • 3. (i) A light source (ii) An optical transmission medium (fiber, waveguide, etc.) (iii) Immobilized biological recognition element (enzymes, antibodies or microbes) (iv) Optical probes (such as a fluorescent marker) for transduction (v) An optical detection system.
  • 4.
  • 5.
  • 6. o Nanoparticles play a significant role in various fields such as biomedical imaging and diagnostics. o Nano-sized biological agents , such as viruses are known to be responsible for a wide variety of human diseases such as flu, AIDS and herpes, and have been used as bio warfare agents. o Accurate quantification of the presence of human viruses such as HIV, herpes or influenza in blood samples is essential for clinical diagnosis and also for vaccine development. o The ability to distinguish between different kinds of viruses present in a sample is also highly desirable. o For example, a single patient may be confected with multiple viral pathogens such as HIV and HCV, and being able to identify and quantify both viruses is crucial for the patient to be treated appropriately.
  • 7. o Optical methods have proved particularly attractive because of their non aggressive nature and high sensitivity. o Optical techniques based on sensing discrete resonance shifts in whispering gallery mode (WGM) , micro cavities due to binding of single virus particles have proved really promising, but they cannot be used to distinguish between viruses of different sizes present in a heterogeneous mixture. o Other optical sensing platforms such as those based on nanoplasmonics or interferometry have proved to be sensitive to single viruses; but while some of them need to be run for a long time and hence are unsuitable for real-time sample characterization, others rely on extensive surface preparation steps or availability of specific antibodies for the target viruses in a sample. o Optical detection of nanoscale biological agents (such as viruses) using light scattering is difficult due to their low scattering cross-section and low index contrast to the surrounding medium.
  • 8. o Nanomaterials used : mixtures of gold and polystyrene particles of different sizes. o The particle size distributions recorded for a mixture of polystyrene particles with mean radii of 50 nm and 75 nm, using the heterodyne (red) and homodyne (green) signals. o Using heterodyne detection, one can clearly resolve the two particle sizes, with very little overlap. o On the other hand, the individual particle distributions are wider in the homodyne case, and hence the distributions partly overlap. o This illustrates the superior size resolution obtainable with heterodyne detection for a heterogeneous mixture of particles.
  • 9. o That heterodyne interferometry can be used very effectively to detect single nanoparticles in solution with high sensitivity and selectivity. o The possibilities of detecting and distinguishing between viruses in solution using heterodyne interferometry. o It is difficult to detect nanoscale biological particles such as single viruses in solution using scattering based techniques. o Due to their weak refractive index contrast with the suspending medium but heterodyne detection helps overcome this difficulty. o Using the heterodyne detection technique, we could successfully detect HIV, Influenza, Sindbis, Vaccinia, Parainfluenza(Sendai), and Baculovirus in separate samples on the single virus level.
  • 10. o The size of most human viruses is in the range of 20−200 nm. o The size distribution recorded for a sample of HIV virus for calibration purposes, the mean radius of HIV particles is taken to be 50 nm, as determined from TEM measurements . o The size distribution for a sample of Sindbis virus. For calibration purposes, the mean radius of Sindbis virus particles is assumed to be 35 nm according to TEM measurements. o To demonstrate the ability to distinguish between HIV and Sindbis viruses in solution, the size distribution for a mixture of the two viruses is recorded . o The two virus types can be resolved. o The results indicate that it is possible to distinguish by size individual viruses in a mixture of different virus types, provided we know, for calibration purposes, the mean size of at least one virus type.
  • 11.
  • 12. o A nozzle continuously delivers viral or synthetic nanoparticles onto a toroidal-shaped microlaser, which translates changes in polarizability into changes in frequency splitting. o The pump light and the split lasing modes are separated using a wavelength division multiplexer (WDM). o Split lasing modes are mixed in a photodetector (PD) leading to a heterodyne beat note signal. o Inset: Experimentally observed green ring due to up- conversion of Er3+ ions traces the WGM along the periphery of the micro resonator.
  • 13. Before the arrival of nanoparticles, there is a single laser mode with constant laser intensity (i). With the arrival of the first nanoparticle, laser mode splits into two ,leading to a beat note whose frequency corresponds to the frequency splitting (ii). Subsequent particle binding event changes the beat frequency (iii). Since the split lasing modes reside in the same micro laser, environmental noise such as temperature fluctuations (illustrated by a heat source placed under the chip) affects both modes in the same way leading to a self-referencing scheme (iv). Thus, although each split mode undergoes spectral shift, the splitting between them does not change, making this detection scheme resistant to environmental noises .
  • 14. The researchers attached red, green or orange nanoparticles to antibodies that specifically bind to proteins from the organisms that cause Ebola, dengue or yellow fever, respectively. Silver nanoparticles are employed and the sizes of the nanoparticles determine their colors. - : Chunwan Yen Hamad-Schifferli and her team at the Massachusetts Institute of Technology, Harvard Medical School and the U.S. Food and Drug Administration
  • 15. • Selectivity and specificity • Remote sensing • Isolation from electromagnetic interference • Fast, real-time measurements • Multiple channels/multi parameters detection • Compact design
  • 16. • Real-time Optical Detection of Single Nanoparticles and Viruses using Heterodyne Interferometry Anirban Mitra1 and Lukas Novotny1,2 Adapted from: Anirban Mitra and Lukas Novotny,“Real-time optical detection of single nanoparticles and viruses using heterodyne interferometry,” Nano- Optics for Enhancing Light-Matter Interactions on a Molecular Scale, B. Di Bartolo et al. (eds.), Chapter 1, p.3–23, NATO Science for Peace and Security Series B: Physics and Biophysics (Springer, Dordrecht, 2013). 1. Department of Physics and Astronomy, University of Rochester, Rochester NY 14627 2. Institute of Optics, University of Rochester, Rochester, NY 14627 https://www.photonics.ethz.ch/fileadmin/user_upload/pdf/Papers/mitra12d.pdf • Detecting single viruses and nanoparticles using whispering gallery microlasers Lina He, Sahin Kaya Ozdemir, Jiangang Zhu, Woosung Kim, Lan Yang* Department of Electrical and Systems Engineering, Washington University in St. Louis, MO 63130, USA * yang@ese.wustl.edu http://arxiv.org/ftp/arxiv/papers/1107/1107.0868.pdf • Optical Detection of Single Nanoparticles and Viruses Filipp V. Ignatovich, David Topham, and Lukas Novotny https://www.photonics.ethz.ch/fileadmin/user_upload/pdf/Papers/ignatovitch06b.pdf http://www.acs.org/