Coherent Raman scattering microscopy

Last updated
Simultaneous two-color label-free stimulated Raman scattering z-stack imaging of mouse ear (red: protein, green: lipid, image is 220 by 220 microns the total depth is 60 microns, the pixel dwell time is 2 microsecond).

Coherent Raman scattering (CRS) microscopy is a multi-photon microscopy technique based on Raman-active vibrational modes of molecules. The two major techniques in CRS microscopy are stimulated Raman scattering (SRS) and coherent anti-Stokes Raman scattering (CARS). SRS and CARS were theoretically predicted and experimentally realized in the 1960s. [1] [2] [3] In 1982 the first CARS microscope was demonstrated. [4] In 1999, CARS microscopy using a collinear geometry and high numerical aperture objective were developed in Xiaoliang Sunney Xie's lab at Harvard University. [5] This advancement made the technique more compatible with modern laser scanning microscopes. [6] Since then, CRS's popularity in biomedical research started to grow. CRS is mainly used to image lipid, protein, and other bio-molecules in live or fixed cells or tissues without labeling or staining. [7] CRS can also be used to image samples labeled with Raman tags, [8] [9] [10] which can avoid interference from other molecules and normally allows for stronger CRS signals than would normally be obtained for common biomolecules. CRS also finds application in other fields, such as material science [11] and environmental science. [12]

Contents

Background

Energy diagrams of spontaneous and coherent Raman scattering processes. Principles energy levels.png
Energy diagrams of spontaneous and coherent Raman scattering processes.

Coherent Raman scattering is based on Raman scattering (or spontaneous Raman scattering). In spontaneous Raman, only one monochromatic excitation laser is used. Spontaneous Raman scattering's signal intensity grows linearly with the average power of a continuous-wave pump laser. In CRS, [7] two lasers are used to excite specific vibrational modes of molecules to be imaged. The laser with a higher photon energy is normally called the pump laser and the laser with a lower photon energy is called Stokes laser. In order to produce a signal their photon energy differences must match the energy of a vibrational mode:

,

where the .

CRS is a nonlinear optical process, where the signal level is normally a function of the product of the powers of the pump and Stokes lasers. Therefore, most CRS microscopy experiments are performed with pulsed lasers, where higher peak power improved the signal levels of CRS significantly. [13]

Coherent anti-Stokes Raman scattering (CARS) Microscopy

Forward and epi-detected CARS Forward and epi-detected CARS.tif
Forward and epi-detected CARS

In CARS, anti-Stokes photons (higher in energy, shorter wavelength than the pump) are detected as signals.

In CARS microscopy, there are normally two ways to detect the newly generated photons. One is called forward-detected CARS, the other called epi-detected CARS. [14] [15] In forward-detected CARS, the generated CARS photons together with pump and Stokes lasers go through the sample. The pump and Stokes lasers are completely blocked by a high optical density (OD) notch filter. The CARS photons are then detected by a photomultiplier tube (PMT) or a CCD camera. In epi-detected CARS, back-scattered CARS photons are redirected by a dichroic mirror or polarizing beam splitter. After high OD filters are used to block back-scattered pump and Stokes lasers, the newly generated photons are detected by a PMT. The signal intensity of CARS has the following relationship with the pump and Stokes laser intensities , the number of molecules in the focus of the lasers and the third order Raman susceptibility of the molecule: [16]

The signal-to-noise ratio (SNR), which is a more important characteristic in imaging experiments depends on the square root of the number of CARS photons generated, which is given below: [16]

There are other non-linear optical processes that also generate photons at the anti-Stokes wavelength. Those signals are normally called non-resonant (NR) four-wave-mixing (FWM) background in CARS microscopy. These background can interfere with the CARS signal either constructively or destructively. [17] However, the problem can be partially circumvented by subtracting the on- and off-resonance images [18] [19] or using mathematical methods to retrieve the background free images. [20]

Stimulated Raman scattering (SRS) microscopy

In SRS, the intensity of the energy transfer from the pump wavelength to the Stokes laser wavelength is measured as a signal. There are two ways to measure SRS signals, one is to measure the increase of power in Stokes laser, which is called stimulated Raman gain (SRG). The other is to measure the decrease of power in the pump laser, which is called stimulated Raman loss (SRL). Since the change of power is on the order of 10−3 to 10−6 compared with the original power of pump and Stokes lasers, a modulation transfer scheme [21] is normally employed to extract the SRS signals. [22] The SRS signal depends on the pump and Stokes laser powers in the following way:

Shot noise limited detection can be achieved if electronic noise from detectors are reduced well below optical noise and the lasers are shot noise limited at the detection frequency (modulation frequency). In the shot noise limited case, the signal-to-noise ratio (SNR) of SRS [16] is

The signal of SRS is free from the non-resonant background which plagues CARS microscopy, although a much smaller non-resonant background from other optical process (e.g. cross-phase modulation, multi-color multi-photon absorption) may exist.

SRS can be detected in either the forward direction and epi directions. In forward-detected SRS, the modulated laser is blocked by a high OD notch filter and the other laser is measured by a photodiode. Modulation transferred from the modulated laser to the originally unmodulated laser is normally extracted by a lock-in amplifier from the output of photodiode. In epi-detected SRS, there are normally two methods to detect the SRS signal. One method is to detect the back-scattered light in front of the objective by a photodiode with a hole at the center. The other method is similar to the epi-detected CARS microscopy, where the back-scattered light goes through the objective and is deflected to the side of the light path, normally with the combination of a polarizing beam splitter and a quarter wave-plate. The Stokes (or pump) laser is then detected after filtering out the pump (or Stokes laser).

Two-color, multi-color, and hyper-spectral CRS microscopy

One pair of laser wavelengths only gives access to a single vibrational frequency. Imaging samples at different wavenumbers can provide a more specific and quantitative chemical mapping of the sample. [23] [24] [25] [26] [27] [28] This can be achieved by imaging at different wavenumbers one after another. This operation always involves some type of tuning: tuning of one of the lasers' wavelengths, tuning of a spectral filtering device, or tuning of the time delay between the pump and Stokes lasers in the case of spectral-focusing CRS. Another way of performing multi-color CRS is to use one picosecond laser with a narrow spectral bandwidth (<1 nm) as pump or Stokes and the other laser with broad spectral bandwidth. In this case, the spectrum of the transmitted broadband laser can be spread by a grating and measured by an array of detectors.

Spectral-focusing CRS

CRS normally use lasers with narrow bandwidth lasers, whose bandwidth < 1 nm, to maintain good spectral resolution ~ 15 cm−1. Lasers with sub 1 nm bandwidth are picosecond lasers. In spectral-focusing CRS, femtosecond pump and Stokes lasers are equally linearly chirped into picosecond lasers. [29] [30] [31] The effective bandwidth become smaller and therefore, high spectral resolution can be achieved this way with femtosecond lasers which normally have a broad bandwidth. The wavenumber tuning of spectral-focusing CRS can be achieved both by changing the center wavelength of lasers and by changing the delay between pump and Stokes lasers.

Applications

Coherent Raman histology

One of the major applications for CRS is label-free histology, which is also called coherent Raman histology, or sometimes stimulated Raman histology. [32] [33] [34] [35] In CRH, CRS images are obtained at lipid and protein images and after some image processing, an image similar to H&E staining can be obtained. Different from H&E staining, CRH can be done on live and fresh tissue and doesn't need fixation or staining.

Cell metabolism

The metabolism of small molecules like glucose, [36] cholesterol, [37] and drugs [38] are studied with CRS in live cells. CRS provide a way to measure molecular distribution and quantities with relatively high throughput.

Myelin imaging

Myelin is rich in lipid. CRS is routinely used to image myelin in live or fixed tissues to study neurodegenerative diseases or other neural disorders. [39] [40] [41]

Pharmaceutical research

The functions of drugs can be studied by CRS too. For example, an anti-leukemia drug imatinib are studied with SRS in leukemia cell lines. [38] The study revealed the possible mechanism of its metabolism in cells and provided insight about ways to improve drug effectiveness.

Raman tags

Even though CRS allows label-free imaging, Raman tags can also be used to boost signal for specific targets. [42] [9] [8] For example, deuterated molecules are used to shift Raman signal to a band where the interference from other molecules is absent. Specially engineered molecules containing isotopes can be used as Raman tags to achieve super-multiplexing multi-color imaging with SRS. [10]

Comparison to confocal Raman microscopy

Confocal Raman microscopy normally uses continuous wave lasers to provide a spontaneous Raman spectrum over a broad wavenumber range for each point in an image. It takes a long time to scan the whole sample, since each pixel requires seconds for data acquisition. The whole imaging process is long and therefore, it is more suitable for samples that do not move. CRS on the other hand measures signals at single wavenumber but allows for fast scanning. If more spectral information is needed, multi-color or hyperspectral CRS can be used and the scanning speed or data quality will be compromised accordingly. [43]

Comparison between SRS and CARS

In CRS microscopy, we can regard SRS and CARS as two aspects of the same process. CARS signal is always mixed with non-resonant four-wave mixing background and has a quadratic dependence on concentration of chemicals being imaged. SRS has much smaller background and depends linearly on the concentration of the chemical being imaged. Therefore, SRS is more suitable for quantitative imaging than CARS. On the instrument side, SRS requires modulation and demodulation (e.g. lock-in amplifier or resonant detector). For multi-channel imaging, SRS requires multichannel demodulation while CARS only needs a PMT array or a CCD. Therefore, the instrumentation required is more complicated for SRS than CARS. [16]

On the sensitivity side, SRS and CARS normally provide similar sensitivities. [44] Their differences are mainly due to detection methods. In CARS microscopy, PMT, APD or CCDs are used as detectors to detect photons generated in the CARS process. PMTs are most commonly used due to their large detection area and high speed. In SRS microscopy, photodiodes are normally used to measure laser beam intensities. Because of such differences, the applications of CARS and SRS are also different. [16]

PMTs normally have relatively low quantum efficiency compared with photodiodes. This will negatively impact the SNR of CARS microscopy. PMTs also have reduced sensitivity for lasers with wavelengths longer than 650 nm. Therefore, with the commonly used laser system for CRS (Ti-sapphire laser), CARS is mainly used to image at high wavenumber region (2800–3400 cm−1). The SNR of CARS microscopy is normally poor for fingerprint imaging (400–1800 cm−1). [16]

SRS microscopy mainly uses silicon photodiode as detectors. Si photodiodes have much higher quantum efficiency than PMTs, which is one of the reasons that the SNR of SRS can be better than CARS in many cases. Si photodiodes also suffer reduced sensitivity when the wavelength of laser is longer than 850 nm. However, the sensitivity is still relatively high and allows for imaging in fingerprint region (400–1800 cm−1). [16]

See also

Related Research Articles

<span class="mw-page-title-main">Optical amplifier</span> Device that amplifies an optical signal

An optical amplifier is a device that amplifies an optical signal directly, without the need to first convert it to an electrical signal. An optical amplifier may be thought of as a laser without an optical cavity, or one in which feedback from the cavity is suppressed. Optical amplifiers are important in optical communication and laser physics. They are used as optical repeaters in the long distance fiber-optic cables which carry much of the world's telecommunication links.

<span class="mw-page-title-main">Raman spectroscopy</span> Spectroscopic technique

Raman spectroscopy is a spectroscopic technique typically used to determine vibrational modes of molecules, although rotational and other low-frequency modes of systems may also be observed. Raman spectroscopy is commonly used in chemistry to provide a structural fingerprint by which molecules can be identified.

<span class="mw-page-title-main">Raman scattering</span> Inelastic scattering of photons by matter

In physics, Raman scattering or the Raman effect is the inelastic scattering of photons by matter, meaning that there is both an exchange of energy and a change in the light's direction. Typically this effect involves vibrational energy being gained by a molecule as incident photons from a visible laser are shifted to lower energy. This is called normal Stokes-Raman scattering.

A Raman laser is a specific type of laser in which the fundamental light-amplification mechanism is stimulated Raman scattering. In contrast, most "conventional" lasers rely on stimulated electronic transitions to amplify light.

Medical optical imaging is the use of light as an investigational imaging technique for medical applications, pioneered by American Physical Chemist Britton Chance. Examples include optical microscopy, spectroscopy, endoscopy, scanning laser ophthalmoscopy, laser Doppler imaging, and optical coherence tomography. Because light is an electromagnetic wave, similar phenomena occur in X-rays, microwaves, and radio waves.

<span class="mw-page-title-main">Two-photon excitation microscopy</span> Fluorescence imaging technique

Two-photon excitation microscopy is a fluorescence imaging technique that is particularly well-suited to image scattering living tissue of up to about one millimeter in thickness. Unlike traditional fluorescence microscopy, where the excitation wavelength is shorter than the emission wavelength, two-photon excitation requires simultaneous excitation by two photons with longer wavelength than the emitted light. The laser is focused onto a specific location in the tissue and scanned across the sample to sequentially produce the image. Due to the non-linearity of two-photon excitation, mainly fluorophores in the micrometer-sized focus of the laser beam are excited, which results in the spatial resolution of the image. This contrasts with confocal microscopy, where the spatial resolution is produced by the interaction of excitation focus and the confined detection with a pinhole.

Coherent anti-Stokes Raman spectroscopy, also called Coherent anti-Stokes Raman scattering spectroscopy (CARS), is a form of spectroscopy used primarily in chemistry, physics and related fields. It is sensitive to the same vibrational signatures of molecules as seen in Raman spectroscopy, typically the nuclear vibrations of chemical bonds. Unlike Raman spectroscopy, CARS employs multiple photons to address the molecular vibrations, and produces a coherent signal. As a result, CARS is orders of magnitude stronger than spontaneous Raman emission. CARS is a third-order nonlinear optical process involving three laser beams: a pump beam of frequency ωp, a Stokes beam of frequency ωS and a probe beam at frequency ωpr. These beams interact with the sample and generate a coherent optical signal at the anti-Stokes frequency (ωpr+ωp-ωS). The latter is resonantly enhanced when the frequency difference between the pump and the Stokes beams (ωp-ωS) coincides with the frequency of a Raman resonance, which is the basis of the technique's intrinsic vibrational contrast mechanism.

Raman amplification is based on the stimulated Raman scattering (SRS) phenomenon, when a lower frequency 'signal' photon induces the inelastic scattering of a higher-frequency 'pump' photon in an optical medium in the nonlinear regime. As a result of this, another 'signal' photon is produced, with the surplus energy resonantly passed to the vibrational states of the medium. This process, as with other stimulated emission processes, allows all-optical amplification. Optical fiber is today most used as the nonlinear medium for SRS for telecom purposes; in this case it is characterized by a resonance frequency downshift of ~11 THz. The SRS amplification process can be readily cascaded, thus accessing essentially any wavelength in the fiber low-loss guiding windows. In addition to applications in nonlinear and ultrafast optics, Raman amplification is used in optical telecommunications, allowing all-band wavelength coverage and in-line distributed signal amplification.

Chemical imaging is the analytical capability to create a visual image of components distribution from simultaneous measurement of spectra and spatial, time information. Hyperspectral imaging measures contiguous spectral bands, as opposed to multispectral imaging which measures spaced spectral bands.

<span class="mw-page-title-main">Supercontinuum</span>

In optics, a supercontinuum is formed when a collection of nonlinear processes act together upon a pump beam in order to cause severe spectral broadening of the original pump beam, for example using a microstructured optical fiber. The result is a smooth spectral continuum. There is no consensus on how much broadening constitutes a supercontinuum; however researchers have published work claiming as little as 60 nm of broadening as a supercontinuum. There is also no agreement on the spectral flatness required to define the bandwidth of the source, with authors using anything from 5 dB to 40 dB or more. In addition the term supercontinuum itself did not gain widespread acceptance until this century, with many authors using alternative phrases to describe their continua during the 1970s, 1980s and 1990s.

<span class="mw-page-title-main">Harmonic generation</span> Nonlinear optical process

Harmonic generation is a nonlinear optical process in which photons with the same frequency interact with a nonlinear material, are "combined", and generate a new photon with times the energy of the initial photons.

<span class="mw-page-title-main">Xiaoliang Sunney Xie</span> Chinese-American biochemist

Xiaoliang Sunney Xie is a Chinese biophysicist well known for his contributions to the fields of single-molecule biophysical chemistry, coherent Raman Imaging and single-molecule genomics. In 2023, Xie renounced his U.S. citizenship in order to reclaim his Chinese citizenship.

<span class="mw-page-title-main">Raman microscope</span> Laser microscope used for Raman spectroscopy

The Raman microscope is a laser-based microscopic device used to perform Raman spectroscopy. The term MOLE is used to refer to the Raman-based microprobe. The technique used is named after C. V. Raman, who discovered the scattering properties in liquids.

A random laser (RL) is a laser in which optical feedback is provided by scattering particles. As in conventional lasers, a gain medium is required for optical amplification. However, in contrast to Fabry–Pérot cavities and distributed feedback lasers, neither reflective surfaces nor distributed periodic structures are used in RLs, as light is confined in an active region by diffusive elements that either may or may not be spatially distributed inside the gain medium.

The technique of vibrational analysis with scanning probe microscopy allows probing vibrational properties of materials at the submicrometer scale, and even of individual molecules. This is accomplished by integrating scanning probe microscopy (SPM) and vibrational spectroscopy. This combination allows for much higher spatial resolution than can be achieved with conventional Raman/FTIR instrumentation. The technique is also nondestructive, requires non-extensive sample preparation, and provides more contrast such as intensity contrast, polarization contrast and wavelength contrast, as well as providing specific chemical information and topography images simultaneously.

Time Stretch Microscopy also known as Serial time-encoded amplified imaging/microscopy or stretched time-encoded amplified imaging/microscopy' (STEAM) is a fast real-time optical imaging method that provides MHz frame rate, ~100 ps shutter speed, and ~30 dB optical image gain. Based on the Photonic Time Stretch technique, STEAM holds world records for shutter speed and frame rate in continuous real-time imaging. STEAM employs the Photonic Time Stretch with internal Raman amplification to realize optical image amplification to circumvent the fundamental trade-off between sensitivity and speed that affects virtually all optical imaging and sensing systems. This method uses a single-pixel photodetector, eliminating the need for the detector array and readout time limitations. Avoiding this problem and featuring the optical image amplification for dramatic improvement in sensitivity at high image acquisition rates, STEAM's shutter speed is at least 1000 times faster than the state - of - the - art CCD and CMOS cameras. Its frame rate is 1000 times faster than fastest CCD cameras and 10 - 100 times faster than fastest CMOS cameras.

Rotating-polarization coherent anti-Stokes Raman spectroscopy, (RP-CARS) is a particular implementation of the coherent anti-Stokes Raman spectroscopy (CARS). RP-CARS takes advantage of polarization-dependent selection rules in order to gain information about molecule orientation anisotropy and direction within the optical point spread function.

<span class="mw-page-title-main">Optical rogue waves</span>

Optical rogue waves are rare pulses of light analogous to rogue or freak ocean waves. The term optical rogue waves was coined to describe rare pulses of broadband light arising during the process of supercontinuum generation—a noise-sensitive nonlinear process in which extremely broadband radiation is generated from a narrowband input waveform—in nonlinear optical fiber. In this context, optical rogue waves are characterized by an anomalous surplus in energy at particular wavelengths or an unexpected peak power. These anomalous events have been shown to follow heavy-tailed statistics, also known as L-shaped statistics, fat-tailed statistics, or extreme-value statistics. These probability distributions are characterized by long tails: large outliers occur rarely, yet much more frequently than expected from Gaussian statistics and intuition. Such distributions also describe the probabilities of freak ocean waves and various phenomena in both the man-made and natural worlds. Despite their infrequency, rare events wield significant influence in many systems. Aside from the statistical similarities, light waves traveling in optical fibers are known to obey the similar mathematics as water waves traveling in the open ocean, supporting the analogy between oceanic rogue waves and their optical counterparts. More generally, research has exposed a number of different analogies between extreme events in optics and hydrodynamic systems. A key practical difference is that most optical experiments can be done with a table-top apparatus, offer a high degree of experimental control, and allow data to be acquired extremely rapidly. Consequently, optical rogue waves are attractive for experimental and theoretical research and have become a highly studied phenomenon. The particulars of the analogy between extreme waves in optics and hydrodynamics may vary depending on the context, but the existence of rare events and extreme statistics in wave-related phenomena are common ground.

Stimulated Raman spectroscopy, also referred to as stimulated Raman scattering (SRS) is a form of spectroscopy employed in physics, chemistry, biology, and other fields. The basic mechanism resembles that of spontaneous Raman spectroscopy: a pump photon, of the angular frequency , which is scattered by a molecule has some small probability of inducing some vibrational transition, as opposed to inducing a simple Rayleigh transition. This makes the molecule emit a photon at a shifted frequency. However, SRS, as opposed to spontaneous Raman spectroscopy, is a third-order non-linear phenomenon involving a second photon—the Stokes photon of angular frequency —which stimulates a specific transition. When the difference in frequency between both photons resembles that of a specific vibrational transition the occurrence of this transition is resonantly enhanced. In SRS, the signal is equivalent to changes in the intensity of the pump and Stokes beams. The signals are typically rather low, of the order of a part in 10^5, thus calling for modulation-transfer techniques: one beam is modulated in amplitude and the signal is detected on the other beam via a lock-in amplifier. Employing a pump laser beam of a constant frequency and a Stokes laser beam of a scanned frequency allows for the unraveling of the spectral fingerprint of the molecule. This spectral fingerprint differs from those obtained by other spectroscopy methods such as Rayleigh scattering as the Raman transitions confer to different exclusion rules than those that apply for Rayleigh transitions.

Pump–probe microscopy is a non-linear optical imaging modality used in femtochemistry to study chemical reactions. It generates high-contrast images from endogenous non-fluorescent targets. It has numerous applications, including materials science, medicine, and art restoration.

References

  1. ↑ Woodbury, Ng. "Ruby operation in the Near IR". Proc. Inst. Radio Eng. 50: 2367.
  2. ↑ Jones, W. J.; Stoicheff, B. P. (1964-11-30). "Inverse Raman Spectra: Induced Absorption at Optical Frequencies". Physical Review Letters. 13 (22): 657–659. Bibcode:1964PhRvL..13..657J. doi:10.1103/PhysRevLett.13.657.
  3. ↑ Maker, P. D.; Terhune, R. W. (1965-02-01). "Study of Optical Effects Due to an Induced Polarization Third Order in the Electric Field Strength". Physical Review. 137 (3A): A801–A818. Bibcode:1965PhRv..137..801M. doi:10.1103/PhysRev.137.A801.
  4. ↑ Manuccia, T. J.; Reintjes, J.; Duncan, M. D. (1982-08-01). "Scanning coherent anti-Stokes Raman microscope". Optics Letters. 7 (8): 350–352. Bibcode:1982OptL....7..350D. doi:10.1364/OL.7.000350. ISSN   1539-4794. PMID   19714017.
  5. ↑ Zumbusch, Andreas; Holtom, Gary R.; Xie, X. Sunney (1999-05-17). "Three-Dimensional Vibrational Imaging by Coherent Anti-Stokes Raman Scattering". Physical Review Letters. 82 (20): 4142–4145. Bibcode:1999PhRvL..82.4142Z. doi:10.1103/physrevlett.82.4142. ISSN   0031-9007.
  6. ↑ Zumbusch, Andreas; Holtom, Gary R.; Xie, X. Sunney (1999-05-17). "Three-Dimensional Vibrational Imaging by Coherent Anti-Stokes Raman Scattering". Physical Review Letters. 82 (20): 4142–4145. Bibcode:1999PhRvL..82.4142Z. doi:10.1103/PhysRevLett.82.4142.
  7. 1 2 Coherent raman scattering microscopy. Cheng, Ji-Xin, Xie, Xiaoliang Sunney. Boca Raton. 13 April 2018. ISBN   978-1-138-19952-1. OCLC   1062325706.{{cite book}}: CS1 maint: location missing publisher (link) CS1 maint: others (link)
  8. 1 2 Hong, Senlian; Chen, Tao; Zhu, Yuntao; Li, Ang; Huang, Yanyi; Chen, Xing (2014). "Live-Cell Stimulated Raman Scattering Imaging of Alkyne-Tagged Biomolecules". Angewandte Chemie International Edition. 53 (23): 5827–5831. doi:10.1002/anie.201400328. ISSN   1521-3773. PMID   24753329.
  9. 1 2 Wei, Lu; Hu, Fanghao; Shen, Yihui; Chen, Zhixing; Yu, Yong; Lin, Chih-Chun; Wang, Meng C; Min, Wei (2014). "Live-cell imaging of alkyne-tagged small biomolecules by stimulated Raman scattering". Nature Methods. 11 (4): 410–412. doi:10.1038/nmeth.2878. ISSN   1548-7091. PMC   4040164 . PMID   24584195.
  10. 1 2 Wei, Lu; Chen, Zhixing; Shi, Lixue; Long, Rong; Anzalone, Andrew V.; Zhang, Luyuan; Hu, Fanghao; Yuste, Rafael; Cornish, Virginia W.; Min, Wei (2017). "Super-multiplex vibrational imaging". Nature. 544 (7651): 465–470. Bibcode:2017Natur.544..465W. doi:10.1038/nature22051. ISSN   0028-0836. PMC   5939925 . PMID   28424513.
  11. ↑ Ling, Jiwei; Miao, Xianchong; Sun, Yangye; Feng, Yiqing; Zhang, Liwu; Sun, Zhengzong; Ji, Minbiao (2019-12-24). "Vibrational Imaging and Quantification of Two-Dimensional Hexagonal Boron Nitride with Stimulated Raman Scattering". ACS Nano. 13 (12): 14033–14040. doi:10.1021/acsnano.9b06337. ISSN   1936-0851. PMID   31725258. S2CID   208035177.
  12. ↑ Zada, Liron; Leslie, Heather A.; Vethaak, A. Dick; Tinnevelt, Gerjen H.; Jansen, Jeroen J.; Boer, Johannes F. de; Ariese, Freek (2018). "Fast microplastics identification with stimulated Raman scattering microscopy". Journal of Raman Spectroscopy. 49 (7): 1136–1144. Bibcode:2018JRSp...49.1136Z. doi: 10.1002/jrs.5367 . ISSN   1097-4555.
  13. ↑ Boyd, Robert W., 1948- (2020). Nonlinear Optics. Elsevier Science & Technology. ISBN   978-0-12-811003-4. OCLC   1148886673.{{cite book}}: CS1 maint: multiple names: authors list (link) CS1 maint: numeric names: authors list (link)
  14. ↑ Cheng, Ji-xin; Volkmer, Andreas; Book, Lewis D.; Xie, X. Sunney (2001). "An Epi-Detected Coherent Anti-Stokes Raman Scattering (E-CARS) Microscope with High Spectral Resolution and High Sensitivity". The Journal of Physical Chemistry B. 105 (7): 1277–1280. doi:10.1021/jp003774a. ISSN   1520-6106.
  15. ↑ Volkmer, Andreas; Cheng, Ji-Xin; Sunney Xie, X. (2001-06-20). "Vibrational Imaging with High Sensitivity via Epidetected Coherent Anti-Stokes Raman Scattering Microscopy". Physical Review Letters. 87 (2): 023901. Bibcode:2001PhRvL..87b3901V. doi:10.1103/physrevlett.87.023901. ISSN   0031-9007.
  16. 1 2 3 4 5 6 7 Min, Wei; Freudiger, Christian W.; Lu, Sijia; Xie, X. Sunney (2011-05-05). "Coherent Nonlinear Optical Imaging: Beyond Fluorescence Microscopy". Annual Review of Physical Chemistry. 62 (1): 507–530. Bibcode:2011ARPC...62..507M. doi:10.1146/annurev.physchem.012809.103512. ISSN   0066-426X. PMC   3427791 . PMID   21453061.
  17. ↑ Evans, Conor L.; Xie, X. Sunney (2008). "Coherent Anti-Stokes Raman Scattering Microscopy: Chemical Imaging for Biology and Medicine". Annual Review of Analytical Chemistry. 1 (1): 883–909. Bibcode:2008ARAC....1..883E. doi:10.1146/annurev.anchem.1.031207.112754. ISSN   1936-1327. PMID   20636101.
  18. ↑ Xie, X. Sunney; Saar, Brian G.; Evans, Conor L.; Ganikhanov, Feruz (2006-06-15). "High-sensitivity vibrational imaging with frequency modulation coherent anti-Stokes Raman scattering (FM CARS) microscopy". Optics Letters. 31 (12): 1872–1874. Bibcode:2006OptL...31.1872G. doi:10.1364/OL.31.001872. ISSN   1539-4794. PMID   16729099.
  19. ↑ Xu, Chris; Xia, Yuanqin; Xia, Fei; Li, Bo; Qin, Yifan (2018-12-24). "Multi-color background-free coherent anti-Stokes Raman scattering microscopy using a time-lens source". Optics Express. 26 (26): 34474–34483. Bibcode:2018OExpr..2634474Q. doi:10.1364/OE.26.034474. ISSN   1094-4087. PMC   6410910 . PMID   30650870.
  20. ↑ Potma, Eric O.; Alfonso Garcia, Alba (2016-06-28). Goda, Keisuke; Tsia, Kevin K. (eds.). "Mapping biological tissues with hyperspectral coherent Raman scattering microscopy (Conference Presentation)". High-Speed Biomedical Imaging and Spectroscopy: Toward Big Data Instrumentation and Management. San Francisco, United States: SPIE. 9720: 14. Bibcode:2016SPIE.9720E..0FP. doi:10.1117/12.2213565. ISBN   9781628419542. S2CID   123694445.
  21. ↑ Fu, Dan; Ye, Tong; Matthews, Thomas E.; Yurtsever, Gunay; Warren, Warren S. (2007). "Two-color, two-photon, and excited-state absorption microscopy". Journal of Biomedical Optics. 12 (5): 054004. Bibcode:2007JBO....12e4004F. doi: 10.1117/1.2780173 . PMID   17994892. S2CID   37036666.
  22. ↑ Freudiger, Christian W.; Min, Wei; Saar, Brian G.; Lu, Sijia; Holtom, Gary R.; He, Chengwei; Tsai, Jason C.; Kang, Jing X.; Xie, X. Sunney (2008-12-19). "Label-Free Biomedical Imaging with High Sensitivity by Stimulated Raman Scattering Microscopy". Science. 322 (5909): 1857–1861. Bibcode:2008Sci...322.1857F. doi:10.1126/science.1165758. ISSN   0036-8075. PMC   3576036 . PMID   19095943.
  23. ↑ Kong, Lingjie; Ji, Minbiao; Holtom, Gary R.; Fu, Dan; Freudiger, Christian W.; Xie, X. Sunney (2013-01-15). "Multicolor stimulated Raman scattering microscopy with a rapidly tunable optical parametric oscillator". Optics Letters. 38 (2): 145–147. Bibcode:2013OptL...38..145K. doi:10.1364/OL.38.000145. ISSN   1539-4794. PMC   3588591 . PMID   23454943.
  24. ↑ Lu, Fa-Ke; Ji, Minbiao; Fu, Dan; Ni, Xiaohui; Freudiger, Christian W.; Holtom, Gary; Xie, X. Sunney (2012-08-10). "Multicolor stimulated Raman scattering microscopy". Molecular Physics. 110 (15–16): 1927–1932. Bibcode:2012MolPh.110.1927L. doi:10.1080/00268976.2012.695028. ISSN   0026-8976. PMC   3596086 . PMID   23504195.
  25. ↑ Lee, Young Jong; Liu, Yuexin; Cicerone, Marcus T. (2007-11-15). "Characterization of three-color CARS in a two-pulse broadband CARS spectrum". Optics Letters. 32 (22): 3370–3372. Bibcode:2007OptL...32.3370L. doi:10.1364/OL.32.003370. ISSN   1539-4794. PMID   18026311.
  26. ↑ Ozeki, Yasuyuki; Umemura, Wataru; Sumimura, Kazuhiko; Nishizawa, Norihiko; Fukui, Kiichi; Itoh, Kazuyoshi (2012-02-01). "Stimulated Raman hyperspectral imaging based on spectral filtering of broadband fiber laser pulses". Optics Letters. 37 (3): 431–433. Bibcode:2012OptL...37..431O. doi:10.1364/OL.37.000431. ISSN   1539-4794. PMID   22297376.
  27. ↑ Wang, Ke; Zhang, Delong; Charan, Kriti; Slipchenko, Mikhail N.; Wang, Ping; Xu, Chris; Cheng, Ji-Xin (2013). "Time-lens based hyperspectral stimulated Raman scattering imaging and quantitative spectral analysis". Journal of Biophotonics. 6 (10): 815–820. doi:10.1002/jbio.201300005. ISSN   1864-0648. PMC   3899243 . PMID   23840041.
  28. ↑ Liao, Chien-Sheng; Slipchenko, Mikhail N; Wang, Ping; Li, Junjie; Lee, Seung-Young; Oglesbee, Robert A; Cheng, Ji-Xin (2015). "Microsecond scale vibrational spectroscopic imaging by multiplex stimulated Raman scattering microscopy". Light: Science & Applications. 4 (3): e265. Bibcode:2015LSA.....4E.265L. doi:10.1038/lsa.2015.38. ISSN   2047-7538. PMC   4498251 . PMID   26167336.
  29. ↑ Hellerer, Thomas; Enejder, Annika M.K.; Zumbusch, Andreas (2004-06-29). "Spectral focusing: High spectral resolution spectroscopy with broad-bandwidth laser pulses". Applied Physics Letters. 85 (1): 25–27. Bibcode:2004ApPhL..85...25H. doi:10.1063/1.1768312. ISSN   0003-6951.
  30. ↑ Andresen, Esben Ravn; Berto, Pascal; Rigneault, Hervé (2011-07-01). "Stimulated Raman scattering microscopy by spectral focusing and fiber-generated soliton as Stokes pulse". Optics Letters. 36 (13): 2387–2389. Bibcode:2011OptL...36.2387A. doi:10.1364/OL.36.002387. ISSN   1539-4794. PMID   21725420.
  31. ↑ Fu, Dan; Holtom, Gary; Freudiger, Christian; Zhang, Xu; Xie, Xiaoliang Sunney (2013-04-25). "Hyperspectral Imaging with Stimulated Raman Scattering by Chirped Femtosecond Lasers". The Journal of Physical Chemistry B. 117 (16): 4634–4640. doi:10.1021/jp308938t. ISSN   1520-6106. PMC   3637845 . PMID   23256635.
  32. ↑ Evans, Conor L.; Xu, Xiaoyin; Kesari, Santosh; Xie, X. Sunney; Wong, Stephen T. C.; Young, Geoffrey S. (2007-09-17). "Chemically-selective imaging of brain structures with CARS microscopy". Optics Express. 15 (19): 12076–12087. Bibcode:2007OExpr..1512076E. doi: 10.1364/OE.15.012076 . ISSN   1094-4087. PMID   19547572.
  33. ↑ Weinigel, M; Breunig, H G; Kellner-Höfer, M; Bückle, R; Darvin, M E; Klemp, M; Lademann, J; König, K (2014-05-01). "In vivo histology: optical biopsies with chemical contrast using clinical multiphoton/coherent anti-Stokes Raman scattering tomography". Laser Physics Letters. 11 (5): 055601. Bibcode:2014LaPhL..11e5601W. doi:10.1088/1612-2011/11/5/055601. ISSN   1612-2011. S2CID   121476537.
  34. ↑ Ji, M.; Orringer, D. A.; Freudiger, C. W.; Ramkissoon, S.; Liu, X.; Lau, D.; Golby, A. J.; Norton, I.; Hayashi, M.; Agar, N. Y. R.; Young, G. S. (2013-09-04). "Rapid, Label-Free Detection of Brain Tumors with Stimulated Raman Scattering Microscopy". Science Translational Medicine. 5 (201): 201ra119. doi:10.1126/scitranslmed.3005954. ISSN   1946-6234. PMC   3806096 . PMID   24005159.
  35. ↑ Orringer, Daniel A.; Pandian, Balaji; Niknafs, Yashar S.; Hollon, Todd C.; Boyle, Julianne; Lewis, Spencer; Garrard, Mia; Hervey-Jumper, Shawn L.; Garton, Hugh J. L.; Maher, Cormac O.; Heth, Jason A. (2017). "Rapid intraoperative histology of unprocessed surgical specimens via fibre-laser-based stimulated Raman scattering microscopy". Nature Biomedical Engineering. 1 (2): 0027. doi:10.1038/s41551-016-0027. ISSN   2157-846X. PMC   5612414 . PMID   28955599.
  36. ↑ Long, Rong; Zhang, Luyuan; Shi, Lingyan; Shen, Yihui; Hu, Fanghao; Zeng, Chen; Min, Wei (2018). "Two-color vibrational imaging of glucose metabolism using stimulated Raman scattering". Chemical Communications. 54 (2): 152–155. doi:10.1039/C7CC08217G. ISSN   1359-7345. PMC   5764084 . PMID   29218356.
  37. ↑ Lee, Hyeon Jeong; Zhang, Wandi; Zhang, Delong; Yang, Yang; Liu, Bin; Barker, Eric L.; Buhman, Kimberly K.; Slipchenko, Lyudmila V.; Dai, Mingji; Cheng, Ji-Xin (2015). "Assessing Cholesterol Storage in Live Cells and C. elegans by Stimulated Raman Scattering Imaging of Phenyl-Diyne Cholesterol". Scientific Reports. 5 (1): 7930. Bibcode:2015NatSR...5E7930L. doi:10.1038/srep07930. ISSN   2045-2322. PMC   4302291 . PMID   25608867.
  38. 1 2 Fu, Dan; Zhou, Jing; Zhu, Wenjing Suzanne; Manley, Paul W.; Wang, Y. Karen; Hood, Tami; Wylie, Andrew; Xie, X. Sunney (2014). "Imaging the intracellular distribution of tyrosine kinase inhibitors in living cells with quantitative hyperspectral stimulated Raman scattering". Nature Chemistry. 6 (7): 614–622. Bibcode:2014NatCh...6..614F. doi:10.1038/nchem.1961. ISSN   1755-4330. PMC   4205760 . PMID   24950332.
  39. ↑ Wang, Haifeng; Fu, Yan; Zickmund, Phyllis; Shi, Riyi; Cheng, Ji-Xin (2005-07-01). "Coherent Anti-Stokes Raman Scattering Imaging of Axonal Myelin in Live Spinal Tissues". Biophysical Journal. 89 (1): 581–591. Bibcode:2005BpJ....89..581W. doi:10.1529/biophysj.105.061911. ISSN   0006-3495. PMC   1366558 . PMID   15834003.
  40. ↑ Belanger, Erik; Crépeau, Joël; Laffray, Sophie; Vallée, Réal; Koninck, Yves De; Côté, Daniel (2012). "Live animal myelin histomorphometry of the spinal cord with video-rate multimodal nonlinear microendoscopy". Journal of Biomedical Optics. 17 (2): 021107–021107–7. Bibcode:2012JBO....17b1107B. doi: 10.1117/1.JBO.17.2.021107 . ISSN   1083-3668. PMID   22463025.
  41. ↑ Tian, Feng; Yang, Wenlong; Mordes, Daniel A.; Wang, Jin-Yuan; Salameh, Johnny S.; Mok, Joanie; Chew, Jeannie; Sharma, Aarti; Leno-Duran, Ester; Suzuki-Uematsu, Satomi; Suzuki, Naoki (2016). "Monitoring peripheral nerve degeneration in ALS by label-free stimulated Raman scattering imaging". Nature Communications. 7 (1): 13283. Bibcode:2016NatCo...713283T. doi:10.1038/ncomms13283. ISSN   2041-1723. PMC   5095598 . PMID   27796305.
  42. ↑ Holtom, Gary R.; Thrall, Brian D.; Chin, Beek-Yoke; Wiley, H. Steven; Colson, Steven D. (2001). "Achieving Molecular Selectivity in Imaging Using Multiphoton Raman Spectroscopy Techniques". Traffic. 2 (11): 781–788. doi:10.1034/j.1600-0854.2001.21106.x. ISSN   1600-0854. PMID   11733044.
  43. ↑ Cui, Meng; Bachler, Brandon R.; Nichols, Sarah R.; Ogilvie, Jennifer P. (2009). "Comparing Coherent and Spontaneous Raman Scattering Under Biological Imaging Conditions". Advances in Imaging. Washington, D.C.: OSA. 34 (6): 773–775. Bibcode:2009OptL...34..773C. doi:10.1364/ntm.2009.nmc4. ISBN   978-1-55752-871-1. PMID   19282928.
  44. ↑ Ozeki, Yasuyuki; Dake, Fumihiro; Kajiyama, Shin'ichiro; Fukui, Kiichi; Itoh, Kazuyoshi (2009-02-24). "Analysis and experimental assessment of the sensitivity of stimulated Raman scattering microscopy". Optics Express. 17 (5): 3651–8. Bibcode:2009OExpr..17.3651O. doi: 10.1364/oe.17.003651 . ISSN   1094-4087. PMID   19259205.
    This page is based on this Wikipedia article
    Text is available under the CC BY-SA 4.0 license; additional terms may apply.
    Images, videos and audio are available under their respective licenses.