Biophotonics

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The term biophotonics [1] denotes a combination of biology and photonics, with photonics being the science and technology of generation, manipulation, and detection of photons, quantum units of light. Photonics is related to electronics and photons. Photons play a central role in information technologies, such as fiber optics, the way electrons do in electronics.

Contents

Biophotonics can also be described as the "development and application of optical techniques, particularly imaging, to the study of biological molecules, cells and tissue". [2] One of the main benefits of using the optical techniques which make up biophotonics is that they preserve the integrity of the biological cells being examined. [3] [4]

Biophotonics has therefore become the established general term for all techniques that deal with the interaction between biological items and photons. This refers to emission, detection, absorption, reflection, modification, and creation of radiation from biomolecular, cells, tissues, organisms, and biomaterials. Areas of application are life science, medicine, agriculture, and environmental science. Similar to the differentiation between "electric" and "electronics," a difference can be made between applications such as therapy and surgery, which use light mainly to transfer energy, and applications such as diagnostics, which use light to excite matter and to transfer information back to the operator. In most cases, the term biophotonics refers to the latter type of application.

Applications

Biophotonics is an interdisciplinary field involving the interaction between electromagnetic radiation and biological materials including: tissues, cells, sub-cellular structures, and molecules in living organisms. [5]

Recent biophotonics research has created new applications for clinical diagnostics and therapies involving fluids, cells, and tissues. These advances are allowing scientists and physicians opportunities for superior, non-invasive diagnostics for vascular and blood flow, as well as tools for better examination of skin lesions. In addition to new diagnostic tools, the advancements in biophotonics research have provided new photothermal, photodynamic, and tissue therapies. [6]

Raman and FT-IR based diagnostics

Raman and FTIR spectroscopy can be applied in many different ways towards improved diagnostics. [7] [8] For example:

  1. Identifying bacterial and fungal infections
  2. Tissue tumor assessment in: skin, liver, bones, bladder etc.
  3. Identifying antibiotic resistances

Other applications

Dermatology

By observing the numerous and complex interactions between light and biological materials, the field of biophotonics presents a unique set of diagnostic techniques that medical practitioners can utilize. Biophotonic imaging provides the field of dermatology with the only non-invasive technique available for diagnosing skin cancers. Traditional diagnostic procedures for skin cancers involve visual assessment and biopsy, but a new laser-induced fluorescence spectroscopy technique allow dermatologists to compare spectrographs of a patient's skin with spectrographs known to correspond with malignant tissue. This provides doctors with earlier diagnosis and treatment options. [5]

"Among optical techniques, an emerging imaging technology based on laser scanning, the optical coherence tomography or OCT imaging is considered to be a useful tool to differentiate healthy from malignant skin tissue".[ attribution needed ] The information is immediately accessible and eliminates the need for skin excision. [5] This also eliminates the need for the skin samples to be processed in a lab which reduces labor costs and processing time.

Furthermore, these optical imaging technologies can be used during traditional surgical procedures to determine the boundaries of lesions to ensure that the entirety of the diseased tissue is removed. This is accomplished by exposing nanoparticles that have been dyed with a fluorescing substance to the acceptable light photons. [6] Nanoparticles that are functionalized with fluorescent dyes and marker proteins will congregate in a chosen tissue type. When the particles are exposed to wavelengths of light that correspond to the fluorescent dye, the unhealthy tissue glows. This allows for the attending surgeon to quickly visually identify boundaries between healthy and unhealthy tissue, resulting in less time on the operating table and higher patient recovery. "Using dielectrophoretic microarray devices, nanoparticles and DNA biomarkers were rapidly isolated and concentrated onto specific microscopic locations where they were easily detected by epifluorescent microscopy".[ attribution needed ] [5]

Optical tweezers

Optical tweezers (or traps) are scientific tools employed to maneuver microscopic particles such as atoms, DNA, bacteria, viruses, and other types of nanoparticles. They use the light's momentum to exert small forces on a sample. This technique allows for the organizing and sorting of cells, the tracking of the movement of bacteria, and the changing of cell structure [9]

Laser micro-scalpel

Laser micro-scalpels are a combination of fluorescence microscopy and a femtosecond laser "can penetrate up to 250 micrometers into tissue and target single cells in 3-D space." [10] The technology, which was patented by researchers at the University of Texas at Austin, means that surgeons can excise diseased or damaged cells without disturbing or damaging healthy surrounding cells in delicate surgeries involving areas such as the eyes and vocal chords. [10]

Photoacoustic microscopy (PAM)

Photoacoustic microscopy (PAM) is an imaging technology that utilizes both laser technology and ultrasound technology. This dual imaging modality is far superior at imaging deep tissue and vascular tissues than previous imaging technologies. The improvement in resolution provides higher quality images of deep tissues and vascular systems, allowing non-invasive differentiation of cancerous tissues vs healthy tissue by observing such things as "water content, oxygen saturation level, and hemoglobin concentration". [11] Researchers have also been able to use PAM to diagnose endometriosis in rats. [6]

Shows the depth of penetration of light through human skin Light Penetration.png
Shows the depth of penetration of light through human skin

Low level laser therapy (LLLT)

Although low-level laser therapy's (LLLT) efficacy is somewhat controversial, the technology can be used to treat wounds by repairing tissue and preventing tissue death. However, more recent studies indicate that LLLT is more useful for reducing inflammation and assuaging chronic joint pain. In addition, it is believed that LLLT could possibly prove to be useful in the treatment of severe brain injury or trauma, stroke, and degenerative neurological diseases. [12]

Photodynamic therapy (PT)

Photodynamic therapy (PT) uses photosynthesizing chemicals and oxygen to induce a cellular reaction to light. It can be used to kill cancer cells, treat acne, and reduce scarring. PT can also kill bacteria, viruses, and fungi. The technology provides treatment with little to no long-term side effects, is less invasive than surgery and can be repeated more often than radiation. Treatment is limited, however, to surfaces and organs that can be exposed to light, which eliminates deep tissue cancer treatments. [13]

Nano particles injected into a tumor to use photothermal therapy Nanoparticles (yellow) targeting and entering cancer cells (blue).png
Nano particles injected into a tumor to use photothermal therapy

Photothermal therapy

Photothermal therapy most commonly uses nanoparticles made of a noble metal to convert light into heat. The nanoparticles are engineered to absorb light in the 700-1000 nm range, where the human body is optically transparent. When the particles are hit by light they heat up, disrupting or destroying the surrounding cells via hyperthermia. Because the light used does not interact with tissue directly, photothermal therapy has few long term side effects and it can be used to treat cancers deep within the body. [14]

FRET

Fluorescence resonance energy transfer, also known as Förster resonance energy transfer (FRET in both cases) is the term given to the process where two excited "fluorophores" pass energy one to the other non-radiatively (i.e., without exchanging a photon). By carefully selecting the excitation of these fluorophores and detecting the emission, FRET has become one of the most widely used techniques in the field of biophotonics, giving scientists the chance to investigate sub-cellular environments.

Biofluorescence

Biofluorescence describes the absorption of ultraviolet or visible light and the sub sequential emission of photons at a lower energy level (S_1 excited state relaxes to S_0 ground state) by intrinsically fluorescent proteins or by synthetic fluorescent molecules covalently attached to a biomarker of interest. Biomarkers are molecules indicative or disease or distress and are a typically monitored systemically in a living organism, or by using an ex vivo tissue sample for microscopy, or in vitro: in the blood, urine, sweat, saliva, interstitial fluid, aqueous humor, or sputum. Stimulating light excites an electron, raising energy to an unstable level. This instability is unfavorable, so the energized electron is returned to a stable state almost as immediately as it becomes unstable. The time delay between excitation and re-emission that occurs when returning to the stable ground state causes the photon that is re-emitted to be a different color (i.e. it relaxes to a lower energy and thus the photon emitted is at a shorter wavelength, as governed by the Plank-Einstein relation ) than the excitation light that was absorbed. This return to stability corresponds with the release of excess energy in the form of fluorescent light. This emission of light is only observable whilst the excitation light is still providing photons to the fluorescent molecule and is typically excited by blue or green light and emits purple, yellow, orange, green, cyan, or red. Biofluorescence is often confused with the following forms of biotic light: bioluminescence and biophosphorescence.

Bioluminescence

Bioluminescence differs from biofluorescence in that it is the natural production of light by chemical reactions within an organism, whereas biofluorescence and biophosphorescence are the absorption and reemission of light from the natural environment.

Biophosphorescence

Biophosphorescence is similar to biofluorescence in its requirement of light at specified wavelengths as a provider of excitation energy. The difference here lies in the relative stability of the energized electron. Unlike with biofluorescence, here the electron retains stability in the forbidden triplet state (unpaired spins), with a longer delay in emitting light resulting in the effect that it continues to “glow-in-the-dark” even long after the stimulating light source has been removed.

Biolasing

A biolaser is when laser light is generated by or from within a living cell. Imaging in biophotonics often relies on laser light, and integration with biological systems is seen as a promising route to enhancing sensing and imaging techniques. Biolasers, like any lasers, require three components: a gain medium, an optical feedback structure and a pump source. For the gain medium, a variety of naturally produced fluorescent proteins can be used in different laser structure. [15] Enclosing an optical feedback structure in a cell has been demonstrated using cell vacuoles, [16] as well as using fully enclosed laser systems such as dye doped polymer microspheres, [17] or semiconductor nanodisks lasers. [18]

Light sources

The predominantly used light sources are beam lights. LEDs and superluminescent diodes also play an important role. Typical wavelengths used in biophotonics are between 600 nm (Visible) and 3000 nm (near IR).

Lasers

Lasers play an increasingly important role in biophotonics. Their unique intrinsic properties like precise wavelength selection, widest wavelength coverage, highest focusability and thus best spectral resolution, strong power densities and broad spectrum of excitation periods make them the most universal light tool for a wide spectrum of applications. As a consequence a variety of different laser technologies from a broad number of suppliers can be found in the market today.

Gas lasers

Major gas lasers used for biophotonics applications, and their most important wavelengths, are:

- Argon Ion laser: 457.8 nm, 476.5 nm, 488.0 nm, 496.5 nm, 501.7 nm, 514.5 nm (multi-line operation possible)

- Krypton Ion laser: 350.7 nm, 356.4 nm, 476.2 nm, 482.5 nm, 520.6 nm, 530.9 nm, 568.2 nm, 647.1 nm, 676.4 nm, 752.5 nm, 799.3 nm

- Helium–neon laser: 632.8 nm (543.5 nm, 594.1 nm, 611.9 nm)

- HeCd lasers: 325 nm, 442 nm

Other commercial gas lasers like carbon dioxide (CO2), carbon monoxide, nitrogen, oxygen, xenon-ion, excimer or metal vapor lasers have no or only very minor importance in biophotonics. Major advantage of gas lasers in biophotonics is their fixed wavelength, their perfect beam quality and their low linewidth/high coherence. Argon ion lasers can also operate in multi-line mode. Major disadvantage are high power consumption, generation of mechanical noise due to fan cooling and limited laser powers. Key suppliers are Coherent, CVI/Melles Griot, JDSU, Lasos, LTB and Newport/Spectra Physics.

Diode lasers

The most commonly integrated laser diodes, which are used for diode lasers in biophotonics are based either on GaN or GaAs semiconductor material. GaN covers a wavelength spectrum from 375 to 488 nm (commercial products at 515 have been announced recently) whereas GaAs covers a wavelength spectrum starting from 635 nm.

Most commonly used wavelengths from diode lasers in biophotonics are: 375, 405, 445, 473, 488, 515, 640, 643, 660, 675, 785 nm.

Laser Diodes are available in 4 classes:

- Single edge emitter/broad stripe/broad area

- Surface emitter/VCSEL

- Edge emitter/Ridge waveguide

- Grating stabilized (FDB, DBR, ECDL)

For biophotonic applications, the most commonly used laser diodes are edge emitting/ridge waveguide diodes, which are single transverse mode and can be optimized to an almost perfect TEM00 beam quality. Due to the small size of the resonator, digital modulation can be very fast (up to 500 MHz). Coherence length is low (typically < 1 mm) and the typical linewidth is in the nm-range. Typical power levels are around 100 mW (depending on wavelength and supplier). Key suppliers are: Coherent, Melles Griot, Omicron, Toptica, JDSU, Newport, Oxxius, Power Technology. Grating stabilized diode lasers either have an lithographical incorporated grating (DFB, DBR) or an external grating (ECDL). As a result, the coherence length will raise into the range of several meters, whereas the linewidth will drop well below picometers (pm). Biophotonic applications, which make use of this characteristics are Raman spectroscopy (requires linewidth below cm-1) and spectroscopic gas sensing.

Solid-state lasers

Solid-state lasers are lasers based on solid-state gain media such as crystals or glasses doped with rare earth or transition metal ions, or semiconductor lasers. (Although semiconductor lasers are of course also solid-state devices, they are often not included in the term solid-state lasers.) Ion-doped solid-state lasers (also sometimes called doped insulator lasers) can be made in the form of bulk lasers, fiber lasers, or other types of waveguide lasers. Solid-state lasers may generate output powers between a few milliwatts and (in high-power versions) many kilowatts.

Ultrachrome lasers

Many advanced applications in biophotonics require individually selectable light at multiple wavelengths. As a consequence a series of new laser technologies has been introduced, which currently looks for precise wording.

The most commonly used terminology are supercontinuum lasers, which emit visible light over a wide spectrum simultaneously. This light is then filtered e.g. via acousto-optic modulators (AOM, AOTF) into 1 or up to 8 different wavelengths. Typical suppliers for this technology was NKT Photonics or Fianium. Recently NKT Photonics bought Fianium, [19] remaining the major supplier of the supercontinuum technology on the market.

In another approach (Toptica/iChrome) the supercontinuum is generated in the infra-red and then converted at a single selectable wavelength into the visible regime. This approach does not require AOTF's and has a background-free spectral purity.

Since both concepts have major importance for biophotonics the umbrella term "ultrachrome lasers" is often used.

Swept sources

Swept sources are designed to continuously change ('sweep') emitted light frequency in time. They typically continuously circle through a pre-defined range of frequencies (e.g., 800 +/- 50 nm). Swept sources in the terahertz regime have been demonstrated. A typical application of swept sources in biophotonics is optical coherence tomography (OCT) imaging.

THz sources

Vibrational spectroscopy in the terahertz (THz) frequency range, 0.1–10 THz, is a fast emerging technique for fingerprinting biological molecules and species. For more than 20 years, theoretical studies predicted multiple resonances in absorption (or transmission) spectra of biological molecules in this range. THz radiation interacts with the low- frequency internal molecular vibrations by exciting these vibrations.

Single photon sources

Single photon sources are novel types of light sources distinct from coherent light sources (lasers) and thermal light sources (such as incandescent light bulbs and mercury-vapor lamps) that emit light as single particles or photons.

Related Research Articles

<span class="mw-page-title-main">Fluorescence</span> Emission of light by a substance that has absorbed light

Fluorescence is the emission of light by a substance that has absorbed light or other electromagnetic radiation. It is a form of luminescence. In most cases, the emitted light has a longer wavelength, and therefore a lower photon energy, than the absorbed radiation. A perceptible example of fluorescence occurs when the absorbed radiation is in the ultraviolet region of the electromagnetic spectrum, while the emitted light is in the visible region; this gives the fluorescent substance a distinct color that can only be seen when the substance has been exposed to UV light. Fluorescent materials cease to glow nearly immediately when the radiation source stops, unlike phosphorescent materials, which continue to emit light for some time after.

<span class="mw-page-title-main">Laser</span> Device which emits light via optical amplification

A laser is a device that emits light through a process of optical amplification based on the stimulated emission of electromagnetic radiation. The word laser is an anacronym that originated as an acronym for light amplification by stimulated emission of radiation. The first laser was built in 1960 by Theodore Maiman at Hughes Research Laboratories, based on theoretical work by Charles H. Townes and Arthur Leonard Schawlow.

<span class="mw-page-title-main">Microscopy</span> Viewing of objects which are too small to be seen with the naked eye

Microscopy is the technical field of using microscopes to view objects and areas of objects that cannot be seen with the naked eye. There are three well-known branches of microscopy: optical, electron, and scanning probe microscopy, along with the emerging field of X-ray microscopy.

<span class="mw-page-title-main">Laser diode</span> Semiconductor laser

A laser diode is a semiconductor device similar to a light-emitting diode in which a diode pumped directly with electrical current can create lasing conditions at the diode's junction.

<span class="mw-page-title-main">Photonics</span> Technical applications of optics

Photonics is a branch of optics that involves the application of generation, detection, and manipulation of light in form of photons through emission, transmission, modulation, signal processing, switching, amplification, and sensing. Photonics is closely related to quantum electronics, where quantum electronics deals with the theoretical part of it while photonics deal with its engineering applications. Though covering all light's technical applications over the whole spectrum, most photonic applications are in the range of visible and near-infrared light. The term photonics developed as an outgrowth of the first practical semiconductor light emitters invented in the early 1960s and optical fibers developed in the 1970s.

<span class="mw-page-title-main">Fluorophore</span> Agents that emit light after excitation by light

A fluorophore is a fluorescent chemical compound that can re-emit light upon light excitation. Fluorophores typically contain several combined aromatic groups, or planar or cyclic molecules with several π bonds.

Plate readers, also known as microplate readers or microplate photometers, are instruments which are used to detect biological, chemical or physical events of samples in microtiter plates. They are widely used in research, drug discovery, bioassay validation, quality control and manufacturing processes in the pharmaceutical and biotechnological industry and academic organizations. Sample reactions can be assayed in 1-1536 well format microtiter plates. The most common microplate format used in academic research laboratories or clinical diagnostic laboratories is 96-well with a typical reaction volume between 100 and 200 µL per well. Higher density microplates are typically used for screening applications, when throughput and assay cost per sample become critical parameters, with a typical assay volume between 5 and 50 µL per well. Common detection modes for microplate assays are absorbance, fluorescence intensity, luminescence, time-resolved fluorescence, and fluorescence polarization.

In chemistry, chromism is a process that induces a change, often reversible, in the colors of compounds. In most cases, chromism is based on a change in the electron states of molecules, especially the π- or d-electron state, so this phenomenon is induced by various external stimuli which can alter the electron density of substances. It is known that there are many natural compounds that have chromism, and many artificial compounds with specific chromism have been synthesized to date. It is usually synonymous with chromotropism, the (reversible) change in color of a substance due to the physical and chemical properties of its ambient surrounding medium, such as temperature and pressure, light, solvent, and presence of ions and electrons.

<span class="mw-page-title-main">Fluorescence microscope</span> Optical microscope that uses fluorescence and phosphorescence

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

A tunable laser is a laser whose wavelength of operation can be altered in a controlled manner. While all laser gain media allow small shifts in output wavelength, only a few types of lasers allow continuous tuning over a significant wavelength range.

<span class="mw-page-title-main">Blue laser</span> Laser which emits light with blue wavelengths

A blue laser emits electromagnetic radiation with a wavelength between 400 and 500 nanometers, which the human eye sees in the visible spectrum as blue or violet.

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

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.

Ultrafast laser spectroscopy is a spectroscopic technique that uses ultrashort pulse lasers for the study of dynamics on extremely short time scales. Different methods are used to examine the dynamics of charge carriers, atoms, and molecules. Many different procedures have been developed spanning different time scales and photon energy ranges; some common methods are listed below.

Robert Alfano is an Italian-American experimental physicist. He is a Distinguished Professor of Science and Engineering at the City College and Graduate School of New York of the City University of New York, where he is also the founding director of the Institute for Ultrafast Spectroscopy and Lasers (1982). He is a pioneer in the fields of Biomedical Imaging and Spectroscopy, Ultrafast lasers and optics, tunable lasers, semiconductor materials and devices, optical materials, biophysics, nonlinear optics and photonics; he has also worked extensively in nanotechnology and coherent backscattering. His discovery of the white-light supercontinuum laser is at the root of optical coherence tomography, which is breaking barriers in ophthalmology, cardiology, and oral cancer detection among other applications. He initiated the field known now as Optical Biopsy

<span class="mw-page-title-main">Photon upconversion</span> Optical process

Photon upconversion (UC) is a process in which the sequential absorption of two or more photons leads to the emission of light at shorter wavelength than the excitation wavelength. It is an anti-Stokes type emission. An example is the conversion of infrared light to visible light. Upconversion can take place in both organic and inorganic materials, through a number of different mechanisms. Organic molecules that can achieve photon upconversion through triplet-triplet annihilation are typically polycyclic aromatic hydrocarbons (PAHs). Inorganic materials capable of photon upconversion often contain ions of d-block or f-block elements. Examples of these ions are Ln3+, Ti2+, Ni2+, Mo3+, Re4+, Os4+, and so on.

Multi-spectral optoacoustic tomography (MSOT), also known as functional photoacoustic tomography (fPAT), is an imaging technology that generates high-resolution optical images in scattering media, including biological tissues. MSOT illuminates tissue with light of transient energy, typically light pulses lasting 1-100 nanoseconds. The tissue absorbs the light pulses, and as a result undergoes thermo-elastic expansion, a phenomenon known as the optoacoustic or photoacoustic effect. This expansion gives rise to ultrasound waves (photoechoes) that are detected and formed into an image. Image formation can be done by means of hardware or computed tomography. Unlike other types of optoacoustic imaging, MSOT involves illuminating the sample with multiple wavelengths, allowing it to detect ultrasound waves emitted by different photoabsorbing molecules in the tissue, whether endogenous or exogenous. Computational techniques such as spectral unmixing deconvolute the ultrasound waves emitted by these different absorbers, allowing each emitter to be visualized separately in the target tissue. In this way, MSOT can allow visualization of hemoglobin concentration and tissue oxygenation or hypoxia. Unlike other optical imaging methods, MSOT is unaffected by photon scattering and thus can provide high-resolution optical images deep inside biological tissues.

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

Photoacoustic microscopy is an imaging method based on the photoacoustic effect and is a subset of photoacoustic tomography. Photoacoustic microscopy takes advantage of the local temperature rise that occurs as a result of light absorption in tissue. Using a nanosecond pulsed laser beam, tissues undergo thermoelastic expansion, resulting in the release of a wide-band acoustic wave that can be detected using a high-frequency ultrasound transducer. Since ultrasonic scattering in tissue is weaker than optical scattering, photoacoustic microscopy is capable of achieving high-resolution images at greater depths than conventional microscopy methods. Furthermore, photoacoustic microscopy is especially useful in the field of biomedical imaging due to its scalability. By adjusting the optical and acoustic foci, lateral resolution may be optimized for the desired imaging depth.

Three-photon microscopy (3PEF) is a high-resolution fluorescence microscopy based on nonlinear excitation effect. Different from two photon excitation microscopy, it uses three exciting photons. It typically uses 1300 nm or longer wavelength lasers to excite the fluorescent dyes with three simultaneously absorbed photons. The fluorescent dyes then emit one photon whose energy is three times the energy of each incident photon. Compared to two-photon microscopy, three-photon microscopy reduces the fluorescence away from the focal plane by , which is much faster than that of two-photon microscopy by . In addition, three-photon microscopy employs near-infrared light with less tissue scattering effect. This causes three photon microscopy to have higher resolution than conventional microscopy.

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Gail McConnell is a Scottish physicist who is Professor of Physics and director of the Centre for Biophotonics at the University of Strathclyde. She is interested in optical microscopy and novel imaging techniques, and leads the Mesolens microscope facility where her research investigates linear and non-linear optics.

<span class="mw-page-title-main">Igor Meglinski</span> British Biomedical Engineer, Biophotonics and Optical Physicist

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References

  1. ↑ Popp, Jurgen; Tuchin, Valery; Chiou, Arthur; Heinemann, Stefan H. (eds) (2011), Handbook of Biophotonics. Vol.1: Basics and Techniques, Wiley-VCH Verlag GmbH & Co. KGaA, p. 686, ISBN   978-3-527-41047-7 {{citation}}: |first4= has generic name (help)
  2. ↑ Goda, Keisuke (2019). "Biophotonics and beyond". APL Photonics. 4 (5): 050401. Bibcode:2019APLP....4e0401G. doi: 10.1063/1.5100614 . ISSN   2378-0967.
  3. ↑ King's College London Centre for Biophotonics
  4. ↑ SPIE (2015). "Gabriel Popescu plenary talk: Bridging Molecular and Cellular Biology with Optics". SPIE Newsroom. doi:10.1117/2.3201503.18.
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  12. ↑ Chung, Hoon; Dai, Tianhong; Sharma, Sulbha K.; Huang, Ying-Ying; Carroll, James D.; Hamblin, Michael R. (February 2012). "The Nuts and Bolts of Low-level Laser (Light) Therapy". Annals of Biomedical Engineering. 40 (2): 516–533. doi:10.1007/s10439-011-0454-7. ISSN   0090-6964. PMC   3288797 . PMID   22045511.
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  14. ↑ Li, Jing-Liang (July–August 2010). "Gold-Nanoparticle-Enhanced Cancer Photothermal Therapy". IEEE Journal of Selected Topics in Quantum Electronics. 16 (4): 989–996. Bibcode:2010IJSTQ..16..989L. doi:10.1109/JSTQE.2009.2030340. hdl: 1959.3/74995 . S2CID   27216810.
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  16. ↑ Humar, Matjaž; Hyun Yun, Seok (27 July 2015). "Intracellular microlasers". Nature Photonics. 9 (9): 572–576. Bibcode:2015NaPho...9..572H. doi:10.1038/NPHOTON.2015.129. PMC   4583142 . PMID   26417383.
  17. ↑ Schubert, Marcel; Steude, Anja; Liehm, Philipp; Kronenberg, Nils M.; Karl, Markus; Campbell, Elaine C.; Powis, Simon J.; Gather, Malte C. (21 July 2015). "Lasing within Live Cells Containing Intracellular Optical Microresonators for Barcode-Type Cell Tagging and Tracking" (PDF). Nano Letters. 15 (8): 5647–5652. Bibcode:2015NanoL..15.5647S. doi:10.1021/acs.nanolett.5b02491. hdl: 10023/9152 . PMID   26186167.
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  19. ↑ "NKT Photonics acquires Fianium". NKT Photonics. 31 March 2016. Archived from the original on 2016-07-07. Retrieved 2016-07-04.
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