Del Mar Photonics - Newsletter Fall 2010 - Newsletter Winter 2010 - Del Mar Photonics at Photonics West 2011
Del Mar Photonics featured customer presentation at Photonics West 2011
Inactivation of encephalomyocarditis virus and herpes simplex virus by using
a visible femtosecond laser
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Paper 7895-28 of Conference 7895
Date: Wednesday, 26 January 2011
Time: 12:10 PM – 12:30 PM
Author(s): Shaw-Wei D. Tsen, Washington Univ. in St. Louis (United States);
Kong-Thon Tsen, Arizona State Univ. (United States)
Recently, a variety of viral systems, including M13 bacteriophage, tobacco
mosaic virus (TMV), human papillomavirus (HPV) and human immunodeficiency virus
(HIV) have been shown to be inactivated by the irradiation of a near-infrared
subpicosecond fiber laser. These experimental results indicated that the
inactivation of viruses by an ultrashort pulsed laser might involve disruption
of their protein coat through laser-induced excitation of large-amplitude
acoustic vibrations. In this work, we report experimental results on the
inactivation of both encephalomyocarditis virus (EMCV) and herpes simplex virus
(HSV) by using a visible femtosecond laser derived from the second harmonic
generation of a cw mode-locked Ti-sapphire laser system. The inactivation of
these viral particles has been demonstrated to depend on the laser exposure time
as well as laser power density. Possible mechanisms for the inactivation will be
discussed.
Del Mar Photonics Trestles femtosecond Ti:Sapphire laser is used by researchers
from Arizona State University to kill viruses and bacteria.
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The research is described in several publications including SPIE newsroom
article:
http://spie.org/x18231.xml?ArticleID=...
K. T. Tsen, Shaw-Wei Tsen, Chih-Long Chang, Chien-Fu Hung, T.-C. Wu, B.
Ramakrishna, and Juliann G. Kiang
A new technique for targeting viral capsids may be applicable to a wide variety
of pathogens.
21 December 2007, SPIE Newsroom. DOI: 10.1117/2.1200711.0928
Most antiviral and antibacterial treatments are only partially successful in
eliminating target pathogens and may raise problems associated with drug
resistance, adverse events, and unwanted side effects. Although UV irradiation
represents an alternative, it lacks selectivity, eliminating unwanted
microorganisms but also damaging other structures while raising concerns over
harmful mutations. New methods to circumvent these limitations are particularly
desirable.
One experimental technique involves microwave absorption with a view to
destroying microorganisms by exciting their vibrational states.1,2 But water,
the basic environmental medium for most undesirable microorganisms, readily
absorbs microwave energy in the range of 10-300GHz, which also happen to be the
typical vibrational frequencies of viral capsids (shells).3,4 In general, it is
extremely difficult to affect the vibrational energy of microorganisms.
Overcoming this drawback will require, in place of microwave excitation, visible
sources in which water is transparent.
To this end, we have employed a low-power visible femtosecond laser system. By
exciting low-frequency vibrational modes of the viral capsid through impulsive
stimulated Raman scattering (ISRS) to a high-energy state, we have succeeded in
inactivating virus. We expect this method to be highly selective and applicable
to any viral or bacterial system.
Optical excitation of coherent lattice or molecular vibrations through
stimulated light scattering can be carried out either by focusing an intense
laser into a medium with a Raman-active vibrational mode or by spatially and
temporally overlapping two laser outputs that possess a suitable frequency
difference. ISRS has been shown to be a viable method for producing
large-amplitude vibrational modes, for both molecules in solution and lattice
vibrations in solid-state systems.5 It has been used to excite coherent acoustic
phonons in ethanol, malachite green and cresyl violet in ethanol,6 and coherent
optical phonons in α-perylene crystal.7 In this process, the electric field from
a femtosecond laser produces an impulsive force through induced polarization.
This mechanical impact coherently excites Raman-active vibrational modes on the
capsid. If the pulse width, spectral width, and intensity of the femtosecond
laser are appropriately chosen, the vibrational modes can be excited to
high-energy states that break the weak links and damage or destroy the capsid,
leading to inactivation of the virus.
We have demonstrated this innovative and unconventional method with M13
bacteriophages, viruses that exclusively infect Escherichia coli.8,9 By using a
very low power visible femtosecond laser with a wavelength of 425nm and a pulse
width of 100fs, we showed that M13 phages became inactive when laser power
density was greater than or equal to 50MW/cm2 (see Figure 1).
Figure 1. Inactivation of the M13 bacteriophage as a function of excitation
laser power density.
Inactivation was determined by plaque counts and depended critically on pulse
width as well as power density of the excitation laser. Figure 2(a) shows the
M13 bacteriophages without, and Figure 2(b) with, laser irradiation. The M13
bacteriophage is a helix-shaped virus with a diameter of about 6nm and length of
about 850nm. Disappearance of the wormlike images in Figure 2 indicates capsid
disintegration.
Figure 2. Atomic force microscope image of M13 bacteriophage (a) without and (b)
with laser irradiation.
Our findings thus suggest a new method for manipulating, controlling, and
inactivating undesirable microorganisms while leaving sensitive mammalian cells
unharmed. It also demonstrates how basic principles of impulsive coherent
acoustic excitation using an ultrafast laser optical system can selectively
alter viral function or inactivate viruses and, potentially, other
microorganisms. Because acoustic capsid vibrations are usually of long
wavelength, they are relatively insensitive to minor local changes, such as
those due to mutations. Therefore, our approach may also be applicable to
drug-resistant strains of microorganisms. Testing is under way. Finally, work in
progress includes efforts to inactivate the human immunodeficiency virus (HIV)
and disinfect the blood supply.
This work is supported by the National Science Foundation.
This video shows was taken during Trestles optimization and training visit.
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Other presentation about using lasers in virus related applications
Silicon-based photonic crystal nanocavities for label-free virus detection
Paper 7888-8 of Conference 7888
Date: Saturday, 22 January 2011
Time: 4:30 PM – 4:45 PM
Author(s): Sudeshna Pal, Amrita R. Yadav, Univ. of Rochester (United States);
Benjamin L. Miller, Univ. of Rochester Medical Ctr. (United States); Philippe M.
Fauchet, Univ. of Rochester (United States)
The optical biosensing platform exploited in this study is a two-dimensional w1
photonic crystal (PhC) waveguide created by removing a central array of holes
from the crystal periodic structure. A nanocavity when coupled to the w1
waveguide, allows light to be transmitted except at frequencies that correspond
to the resonant mode of the cavity. This PhC nanocavity design is extremely
sensitive and allows multiplexed detection of analytes on a single biosensing
platform. The fabricated device has been tested with human papillomavirus (HPV)
virus-like particles (VLPs) to study the sensor response in virus detection.
Preliminary results show an average resonant red-shift of ~ 3 nm at high VLP
concentrations with the device thus indicating successful detection of the VLPs.
LED-interferometric reflectance imaging sensor for label-free detection of
nanoparticles
Paper 7888-16 of Conference 7888
Date: Sunday, 23 January 2011
Time: 11:15 AM – 11:30 AM
Author(s): George Daaboul, Boston Univ. (United States); Priscilla F. Renda,
Russell Graef, MITRE Corp. (United States); Abdulkadir Yurt, Xirui Zhang, Carlos
Lopez, John H. Connor, Boston Univ. (United States); Grace M. Hwang, MITRE Corp.
(United States); M. Selim Unlu, Boston Univ. (United States)
We report a simple wide-field phase imaging technique, LED-Interferometric
Reflectance Imaging Sensor (LED-IRIS), that utilizes on-chip common path
interferometry for real-time detection and sizing of low-index particles such as
viruses. We demonstrate nanoparticle sizing from 70nm-200nm in diameter and also
resolve hundreds of individual H1N1 viruses over a wide area in a single
experiment. An immunoassay is being developed for specific-capture and detection
of single H1N1 virus using various probes multiplexed on the same substrate.
Approved for Public Release: 10-2641. Distribution Unlimited. ©2010 The MITRE
Corporation. All rights reserved.
MS2 bacteriophage as a delivery vessel of porphyrins for photodynamic therapy
Paper 7886-41 of Conference 7886
Date: Sunday, 23 January 2011
Time: 5:30 PM
Author(s): Brian A. Cohen, Alain E. Kaloyeros, Magnus Bergkvist, Univ. at Albany
(United States)
We have selected the MS2 bacteriophage as a potential candidate for use as a
nanoscale delivery vessel of photoactive compounds for site-specific
photodynamic therapy. MS2 was chosen for two reasons: (1) a series of pores on
the capsid exterior large enough to allow the PDT agents access to the interior
and; (2) there is a 7 nm diameter void space inside the capsid large enough for
the loading of hundreds of photoactive compounds. The research presented here
investigates the reactive oxygen species photogeneration by a porphyrin
encapsulated inside MS2.
Improved signal-to-noise detection of single virion using microcavities
Paper 7908-24 of Conference 7908
Date: Thursday, 27 January 2011
Time: 9:30 AM – 9:50 AM
Author(s): Tao Lu, Univ. of Victoria (Canada) and California Institute of
Technology (United States); Hansuek Lee, Tong Chen, Ji Hun Kim, California
Institute of Technology (United States); Steven Herchak, Univ. of Victoria
(Canada); Kerry Vahala, California Institute of Technology (United States)
Using a stable reference interferometer to monitor cavity resonance shift in
real time, one can suppress the influence of laser jitter noise and achieve
sub-femtometer precision of the resonance wavelength measurement. Using this
technique, detection of Influenza A virion with signal-to-noise-ratio exceeding
30:1 has been demonstrated using a silica microtoroid as an ultra-high-Q
microcavity sensor. Binding of polystyrene nanobeads with radii as small as 25nm
is also studied.
Nano-LISA for in vitro diagnostic applications
Paper 7899-59 of Conference 7899
Date: Tuesday, 25 January 2011
Time: 8:45 AM – 9:00 AM
Author(s): Saher M. Maswadi, Randolph D. Glickman, The Univ. of Texas Health
Science Ctr. at San Antonio (United States); Norman Barsalou, William R. Elliott
III, Naval Health Research Ctr. Detachment (United States)
We previously investigated the detection of pathogenic agents, utilizing laser
spectrscopy and antibody-coupled gold nanorods (NR) as a contrast agent as a
contrast agent specifically targeted to the antigen of interest. The Nano-LISA
(Nanoparticle Linked Immunosorbent Assay) method has been adapted to detect
three very common blood-borne viral infectious agents, i.e. human T-lymphotropic
virus (HTLV), human immunodeficiency virus (HIV) and hepatitis-B (Hep-B). A
working laboratory prototype of a Nano-LISA microplate reader-sensor has been
assembled and has been tested with the model panel of the infectious agents.
Thus, adequate detection sensitivity, as well as lack of non-specific
cross-reaction between antigens, has been demonstrated for the OA microplate
reader-sensor, and supports the use of Nano-LISA as a clinical in vitro
diagnostic technique.
Integrated lab-on-a-chip: a combined sample preparation and PCR system as an
ultrafast analytical tool for pathogen detection
Paper 7929-1 of Conference 7929
Date: Sunday, 23 January 2011
Time: 2:30 PM – 3:00 PM
Author(s): Holger Becker, Nadine Hlawatsch, Richard Klemm, Claudia Gärtner,
microfluidic ChipShop GmbH (Germany)
The overall aim is the realization of a reliable, ultrafast, and portable system
for the identification of pathogens and other B-agents at the point of interest.
PCR is the method to be used for the unambiguous identification of e.g.
bacteria, and viruses. Miniaturization is the way to include the overall
analysis process, from sample preparation to detection, on a
microtiterplate-sized consumable device and to allow to carry out the analysis
without the need for an equipped biological laboratory.
Integrated lab-on-a-chip: a combined sample preparation and PCR system as an
ultrafast analytical tool for pathogen detection
Paper 7888-1 of Conference 7888
Date: Sunday, 23 January 2011
Time: 2:30 PM – 3:00 PM
Author(s): Holger Becker, Nadine Hlawatsch, Richard Klemm, Claudia Gärtner,
microfluidic ChipShop GmbH (Germany)
The overall aim is the realization of a reliable, ultrafast, and portable system
for the identification of pathogens and other B-agents at the point of interest.
PCR is the method to be used for the unambiguous identification of e.g.
bacteria, and viruses. Miniaturization is the way to include the overall
analysis process, from sample preparation to detection, on a
microtiterplate-sized consumable device and to allow to carry out the analysis
without the need for an equipped biological laboratory.
An automated wide-field, time-gated, optically sectioning, fluorescence
lifetime imaging multiwell plate reader for high-content analysis of
protein-protein interactions
Paper 7904-61 of Conference 7904
Date: Monday, 24 January 2011
Time: 5:30 PM
Author(s): Sunil Kumar, Imperial College London (United Kingdom); Dominic R.
Alibhai, Imperial College London (United Kingdom) and Pfizer Group Ltd. (United
Kingdom); Clifford B. Talbot, James A. Mcginty, Ian H. Munro, Yuriy Alexandrov,
Anca Margineanu, Imperial College London (United Kingdom); Ted Murray, Frank
Stuhmeier, Pfizer Group Ltd. (United Kingdom); Christopher W. Dunsby, Mark A.
Neil, Paul M. W. French, Imperial College London (United Kingdom)
We describe an optically-sectioned FLIM multiwell plate reader applied to high
content analysis and FRET that combines Nipkow microscopy with wide-field
time-gated FLIM and acquires sectioned FLIM images in <10 s/well, requiring only
~11 minutes to read a 96 well plate. It has been applied to study the formation
of immature HIV virus like particles (VLPs) in live cells by monitoring Gag-Gag
protein interactions using FLIM FRET of HIV-1 Gag transfected with CFP or YFP.
VLP formation results in FRET between closely packed Gag proteins, as confirmed
by our FLIM analysis that includes automatic image segmentation.
Bioconjugation of ultra-high-Q optical microcavities for label-free sensing
Paper 7888-2 of Conference 7888
Date: Saturday, 22 January 2011
Time: 2:00 PM – 2:15 PM
Author(s): Heather K. Hunt, Andrea M. Armani, The Univ. of Southern California
(United States)
The development of label-free biosensors with high sensitivity and specificity
is of significant interest for medical diagnostics and environmental monitoring,
where rapid and real-time detection of antigens, bacteria, viruses, etc., is
necessary. Ultra-high-Q optical microcavities are uniquely suited to sensing
applications, but previous efforts in this area have focused on the development
of the sensor itself. Here, we demonstrate a facile method to impart specificity
to optical microcavities, without adversely impacting their optical performance.
This work represents one of the first examples of non-physisorption-based
bioconjugation of optical microtoroid resonators, which can be used for the
label-free detection of biomolecules.
A novel evanescent field biosensor with an integrated photodetector array
Paper 7888-5 of Conference 7888
Date: Saturday, 22 January 2011
Time: 3:30 PM – 4:00 PM
Author(s): Kevin L. Lear, Rongjin Yan, David S. Dandy, N. Scott Lynn, Richard A.
Slayden, Luke C. Kingry, Colorado State Univ. (United States)
A label-free, evanescent field biosensor is implemented using SiNx/SiO2 optical
waveguides in a conventional silicon integrated circuit manufacturing process.
Rather than surface plasmon, interference, or resonance phenomena, the
transduction mechanism relies on leaky-mode coupling to an array of
photodetectors buried under the waveguide. Changes in surface refractive index
locally modulate photocurrent, motivating naming the device a local evanescent
array coupled (LEAC) sensor. Operation has been demonstrated using ~1 nm average
thickness protein films as well as tuberculosis antigen and antibody capture
probes. Preliminary investigations on virus detection are also reported as part
of research to develop a multi-pathogen detection platform.
Plasmonic enhanced femtosecond-laser optoporation and transfection of human
melanoma cells
Paper 7925-17 of Conference 7925
Date: Sunday, 23 January 2011
Time: 4:30 PM – 4:50 PM
Author(s): Judith Baumgart, Ecole Polytechnique de Montréal (Canada); Laure
Humbert, Royal Victoria Hospital (Canada); Bastien St.-Louis Lalonde, Ecole
Polytechnique de Montréal (Canada); Jean-Jaques Lebrun, Royal Victoria Hospital
(Canada); Michel Meunier, Ecole Polytechnique de Montréal (Canada)
Melanoma is a complex and aggressive cancer and over the past 50 years, its
incidence in most developed countries has increased faster than any other
cancer. We have investigated the use of a femtosecond (fs) laser to create
localized small holes in the membranes of targeted cells to develop a virus-free
technique to allow transfer of genetic material for treating these cancer cells
with high efficiency and minimal collateral damage. This plasmonic enhanced fs
laser process is efficient and highly selective with high cell viability, up to
90%. An optimum perforation rate with efficient molecule uptake was found for
different types of gold nanostructures, spherical (100-200nm) and rod shaped
(10x40nm).
Application of field-modulated birefringence and light scattering to
biosensing
Paper 7888-24 of Conference 7888
Date: Sunday, 23 January 2011
Time: 4:15 PM – 4:30 PM
Author(s): Louis H. Strong, Daniel B. Hall, Clark Edson, Gyula Varadi, Radiation
Monitoring Devices, Inc. (United States)
Superparamagnetic nanoparticles (NPs) coated with surface ligands are shown to
be an effective means to impart magnetic field modulation to optical signals
from targeted receptor complexes. The resulting temporally modulated signals can
be used for a number of important high throughput applications in bio-sensing
including: detecting (weaponized) viruses, screening recombinant libraries of
proteins, identifying pathogenic conversions of microbes, and monitoring gene
amplification. We compare the results of two dynamic methods of measuring target
binding to NPs: birefringence and field modulated light scattering (FMLS). These
measurements reflect complementary manifestations of NP alignment (orientation)
and de-alignment (relaxation) dynamics. Birefringence originates from the
specific crystalline properties of a small subset of paramagnetic NPs (for
example, maghemite ) when oriented in a magnetic field. Upon quenching the
field, it decays at a rate exhibiting the Debye-Stokes-Einstein rotational
relaxation constant of the target-NP complex. Birefringence relaxation reflects
the particle dynamics of the mixed suspension of NPs, with signal components
weighted with respect to both free and complexed NP size distributions. FMLS
relaxation signals, on the other hand, originate predominately from the inherent
optical anisotropy of the target complexes, show little contribution from
non-complexed NPs, and provide a more direct and accurate method for determining
target receptor concentrations. Several illustrations of the broad range of
applications possible using these dynamic measurements and the kind of
information to be derived from each detection modality will be discussed.
Application of field-modulated birefringence and light scattering to
biosensing
Paper 7929-24 of Conference 7929
Date: Sunday, 23 January 2011
Time: 4:15 PM – 4:30 PM
Author(s): Louis H. Strong, Daniel B. Hall, Clark Edson, Gyula Varadi, Radiation
Monitoring Devices, Inc. (United States)
Superparamagnetic nanoparticles (NPs) coated with surface ligands are shown to
be an effective means to impart magnetic field modulation to optical signals
from targeted receptor complexes. The resulting temporally modulated signals can
be used for a number of important high throughput applications in bio-sensing
including: detecting (weaponized) viruses, screening recombinant libraries of
proteins, identifying pathogenic conversions of microbes, and monitoring gene
amplification. We compare the results of two dynamic methods of measuring target
binding to NPs: birefringence and field modulated light scattering (FMLS). These
measurements reflect complementary manifestations of NP alignment (orientation)
and de-alignment (relaxation) dynamics. Birefringence originates from the
specific crystalline properties of a small subset of paramagnetic NPs (for
example, maghemite ) when oriented in a magnetic field. Upon quenching the
field, it decays at a rate exhibiting the Debye-Stokes-Einstein rotational
relaxation constant of the target-NP complex. Birefringence relaxation reflects
the particle dynamics of the mixed suspension of NPs, with signal components
weighted with respect to both free and complexed NP size distributions. FMLS
relaxation signals, on the other hand, originate predominately from the inherent
optical anisotropy of the target complexes, show little contribution from
non-complexed NPs, and provide a more direct and accurate method for determining
target receptor concentrations. Several illustrations of the broad range of
applications possible using these dynamic measurements and the kind of
information to be derived from each detection modality will be discussed.
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