ArticlePDF Available
Grand Challenges and Opportunities
in Biophotonics
Bahman Anvari *
Department of Bioengineering, University of California, Riverside, Riverside, CA, United States
Keywords: biology, environment, light, lasers, microscopy, medicine, optical imaging, therapeutics
Biophotonics is the scienticeld at the interface of life and light sciences. It encompasses the use of
light as the energy source that enables fundamental studies and application developments in
biological, pharmaceutical, environmental and agricultural sciences, and medicine. While the
term is contemporary, some of the earliest recorded history of the eld probably dates back to
the 17th century with the rst microbial observations by Antony van Leeuwenhoek using single
lenses (Ford, 1985). In 1903, The Noble Prize in Physiology or Medicine was awarded to Niels Ryber
Finsen in recognition of his contribution to the treatment of diseases, especially lupus vulgaris, with
concentrated light radiation, whereby he has opened a new avenue for medical science
1
. Fast
forward to 21st century where The Noble Prize in Chemistry was awarded for the discovery and
development of the green uorescent protein
2
in 2008, and for the development of super-resolved
uorescence microscopy
3
in 2014. The Noble Prize in Physics in 2018 was partly awarded to Arthur
Ashkin for the optical tweezers and their application to biological systems
4
.
At the most fundamental level, the nature of the interaction of light with biological and organic
matters provides the basis for both basic and translational work in biophotonics. These interactions
involve the absorption and scattering of photons, and have led to the development of diverse
technologies including various types of optical spectroscopy methods such as UV-VIS-IR
spectroscopy, Fourier Transform Infrared Spectroscopy (FTIR), and Raman scattering;
microscopy methods including confocal and multiphoton, uorescence lifetime imaging (FLIM),
and nanoscale optical microscopy (Hermann and Gordon, 2018); and clinical diagnostic and
imaging technologies such as pulse oximetry, optical coherence tomography (OCT) (Huang
et al., 1991), and uorescence-guided surgery (Landau et al., 2016).
On the therapeutic side, Leon Goldman pioneered the use of lasers in dermatology (Goldman
et al., 1963). Soon after, clinical applications of lasers were extended to ophthalmology for treatment
of diabetic retinopathy (LEsperance, 1969) and photodynamic therapy, and more recently to
photoimmunotherapy (Kobayashi and Choyke, 2019;Xu et al., 2020). Optical neuromodulation
including optogenetics and non-genetic photostimulation methods for optical manipulation of
cellular and sub-cellular activities have recently emerged (Boyden et al., 2005;Jiang et al., 2019).
Despite these remarkable achievements and tremendous contributions to life sciences and
medicine, there are signicant challenges and yet exciting opportunities in biophotonics.
Inherently, depth of optical penetration in biological materials remains limited to a few cm.
Furthermore, increased optical penetration depth is accompanied by decreased spatial resolution.
Methodologies that can enable increased penetration depth and spatial resolution would have great
impact in photo-therapeutics and optical imaging applications. In vivo measurements of optical
Edited and reviewed by:
Marco Peccianti,
University of Sussex, United Kingdom
*Correspondence:
Bahman Anvari
anvarib@ucr.edu
Specialty section:
This article was submitted to
Biophotonics,
a section of the journal
Frontiers in Photonics
Received: 01 June 2021
Accepted: 11 June 2021
Published: 22 June 2021
Citation:
Anvari B (2021) Grand Challenges and
Opportunities in Biophotonics.
Front. Photonics 2:719131.
doi: 10.3389/fphot.2021.719131
1
The Nobel Prize in Physiology or Medicine 1903 [Online]. Available: https://www.nobelprize.org/prizes/medicine/1903/
summary/.
2
The Nobel Prize in Chemistry 2008 [Online]. Available: https://www.nobelprize.org/prizes/chemistry/2008/summary/.
3
The Nobel Prize in Chemistry 2014 [Online]. Available: https://www.nobelprize.org/prizes/chemistry/2014/summary/.
4
The Nobel Prize in Physics 2018 [Online]. Available: https://www.nobelprize.org/prizes/physics/2018/summary/.
Frontiers in Photonics | www.frontiersin.org June 2021 | Volume 2 | Article 7191311
SPECIALTY GRAND CHALLENGE
published: 22 June 2021
doi: 10.3389/fphot.2021.719131
properties can lead to development of real time diagnostics,
guided-therapies and evaluation of therapeutic interventions.
Multiplexed molecular sensing and development of new
probes that can provide high sensitivity and specicity present
another arena for further developments. Compact and
miniatured devices, and wearable and implantable sensors
would be of immense value for use at home, and at point-of-
care and resource-limited settings. The current COVID-19
pandemic illustrates the need for such practical, inexpensive,
and easy-to-use devices that can provide rapid and accurate
diagnostics.
Light-based theranostic technologies integrated with
molecular and genomic proling would provide capabilities for
combined sensing/diagnostics/imaging and therapeutics on
personalized basis. Photonic technologies will have important
roles in high throughput drug screening, in vivo tracking of drugs
biodistribution, and mediating localized and controlled-release of
drugs. A better understanding of the immune response and the
role of various inammatory cells and signaling biomolecules to
light can lead to development of more effective phototherapeutic
methods.
The progress in articial intelligence, including machine
learning, data mining, big data analysis, and computational
power provide opportunities for closer interactions and
integrations with biophotonics toward automated feature and
pattern identications that may otherwise not be possible. Such
interactions will also be increasingly useful for applications in
environmental monitoring including the assessment of climate
change and marine life, and in food and agricultural monitoring
for pathogens and toxins detections as well as soil and vegetation
evaluation. These examples highlight the multidisciplinary nature
of biophotonics and the opportunities for collaborations among
scientists with various expertise, as well as the need for
development of educational curricula that emphasize multiple
disciplines to train the future generations of scientists working in
this eld.
The immense capabilities of biophotonics have been
recognized by specic government agencies to support
biophotonics research. A particular example is the
Biophotonics Program at United States National Science
Foundation whose goal is to explore the research frontiers in
photonics principles, engineering and technology that are
relevant for critical problems in elds of medicine, biology and
biotechnology.Funding through appropriate governmental
agencies will be needed to tackle these grand challenges and
ultimately impact human health and the environment on our
planet. The eld of biophotonics continues to grow and embraces
new interested scientists.
AUTHOR CONTRIBUTIONS
The author conrms being the sole contributor of this work and
has approved it for publication.
REFERENCES
Boyden, E. S., Zhang, F., Bamberg, E., Nagel, G., and Deisseroth, K. (2005).
Millisecond-timescale, Genetically Targeted Optical Control of Neural Activity.
Nat. Neurosci. 8, 12631268. doi:10.1038/nn1525
Ford, B. J. (1985). Single Lens: The story of the Simple Microscope. London:
HarperCollins.
Goldman, L., Blaney, D. J., Kindel, D. J., Richeld, D., and Franke, E. K. (1963).
Pathology of the Effect of the Laser Beam on the Skin. Nature 197, 912914.
doi:10.1038/197912b0
Hermann, R. J., and Gordon, M. J. (2018). Nanoscale Optical Microscopy and
Spectroscopy Using Near-Field Probes. Annu. Rev. Chem. Biomol. Eng. 9,
356387. doi:10.1146/annurev-chembioeng-060817-084150
Huang, D., Swanson, E., Lin, C., Schuman, J., Stinson, W., Chang, W., et al. (1991).
Optical Coherence Tomography. Science 254, 11781181. doi:10.1126/
science.1957169
Jiang, Y., Parameswaran, R., Li, X., Carvalho-De-Souza, J. L., Gao, X., Meng, L.,
et al. (2019). Nongenetic Optical Neuromodulation with Silicon-Based
Materials. Nat. Protoc. 14, 13391376. doi:10.1038/s41596-019-0135-9
Kobayashi, H., and Choyke, P. L. (2019). Near-Infrared Photoimmunotherapy of
Cancer. Acc. Chem. Res. 52, 23322339. doi:10.1021/acs.accounts.9b00273
Landau, M. J., Gould, D. J., and Patel, K. M. (2016). Advances in Fluorescent-Image
Guided Surgery. Ann. Transl. Med. 4, 392. doi:10.21037/atm.2016.10.70
Lesperance, F. A., Jr. (1969). Treatment of Ophtalmic Vascular Diseases by Argon
Laser Photocoagulation. Trans. Am. Acad. Ophthalmol. Otolaryngol. 73, 10771096.
Xu, X., Lu, H., and Lee, R. (2020). Near Infrared Light Triggered Photo/immuno-
Therapy toward Cancers. Front. Bioeng. Biotechnol. 8, 488. doi:10.3389/
fbioe.2020.00488
Conict of Interest: The author declares that the research was conducted in the
absence of any commercial or nancial relationships that could be construed as a
potential conict of interest.
Copyright © 2021 Anvari. This is an open-access article distributed under the terms
of the Creative Commons Attribution License (CC BY). The use, distribution or
reproduction in other forums is permitted, provided the original author(s) and the
copyright owner(s) are credited and that the original publication in this journal is
cited, in accordance with accepted academic practice. No use, distribution or
reproduction is permitted which does not comply with these terms.
Frontiers in Photonics | www.frontiersin.org June 2021 | Volume 2 | Article 7191312
Anvari Biophotonics
... Biophotonics is the scientific application of optics in life sciences. It is a breakthrough in biological, pharmaceutical, environmental and agricultural science, and in the medical area [1]. This field can be traced back to the 1600s when Antonie van Leeuwenhoek created the single-lens microscope to observe bacteria and protozoa [2]. ...
... Deep optical penetration has its limitations in spatial resolution. As the penetration depth increases, the resolution becomes lower, thus limiting the application of optical imaging and phototherapeutics [1,102,103]. There is also an issue in in-vivo optical imaging as there is scattering in the tissues because of the difference in the refractive index while light can also be absorbed by the hemoglobin and endogenous fluorophores [104]. ...
Article
Full-text available
Biophotonics procures wide practicability in life sciences and medicines. The contribution of biophotonics is well recognized in various Nobel Prizes. Therefore, this paper aims to conduct a bibliometric analysis of biophotonics publications. The scientific database used is the Web of Science database. Harzing's Publish or Perish and VOSviewer are the bibliometric tools used in this analysis. This study found an increasing trend in the number of publications in recent years as the number of publications peaked at 347 publications in 2020. Most of the documents are articles (3361 publications) and proceeding papers (1632 publications). The top three subject areas are Optics (3206 publications), Engineering (1706 publications) and Radiology, Nuclear Medicine, and Medical Imaging (1346 publications). The United States has the highest number of publications (2041 publications) and citation impact (38.07 citations per publication; h-index: 125). The top three publication titles are Proceedings of SPIE (920 publications), Journal of Biomedical Optics (599 publications), and Proceedings of the Society of Photo Optical Instrumentation Engineers SPIE (245 publications). The potential areas for future research include to overcome the optical penetration depth issue and to develop publicly available biosensors for the detection of common diseases.
... (6) Besides, this work intends to draw attention to the "ferryl peroxide molecules" from those nutritional aspects that these important free radicals are continuously produced during all "Cytc plus H 2 O 2 " reactions at both intra and extracellular levels in all living organisms owning mitochondria. They can regulate not only the energy metabolism and cell survival, but their "side and end" products, the "biophotons" may also have an importance which is still hardly explored [20]. Thus, the plant peroxidases of wines may have individual, dose dependent and lifelong nutritional influences on these vital processes of all persons consuming wines. ...
... These results draw attention to notice the hardly estimated extracellular importance of Cytc being a marker of mitochondria and cellular damages [26,27]. Thus, the chance for real interactions between the plant peroxidases of wines and the naturally produced Cytc and H 2 O 2 molecules in humans cannot be denied since the production of H 2 O 2 is also continuous in the organism, and the interactions between Cytc and hydrogen peroxide are permanent, resulting in "ferryl-peroxide radicals" [8] and biophotons [20]. One nutritional merit of the present work can be the chemical demonstration of the remarkable stimulating effects of various wines on these interactions. ...
Article
Full-text available
It was suggested that the measurement of chemiluminescence induced by cytochrome c plus hydrogen peroxide might characterize the peroxidase activity of various wines added and, furthermore, the Botrytis cinerea related quality of Aszú wines of Tokaj in Hungary. The chemiluminescence produced by cytochrome c plus hydrogen peroxide reaction was detected by a luminometer. The chemiluminescence stimulating effects of various wines (n = 146) including Aszú wines from Tokaj and other Hungarian white and red wines were compared and analysed by using an “Index of Stimulation”. The content of gluconic acid in Aszú wines was determined colorimetrically. All types of wines tested could stimulate the intensity of chemiluminescence induced by the cytochrome c plus hydrogen peroxide expressed by an Index of Stimulation. This effect could mainly be regarded as a result of the peroxidase activity of wines. The highest values of the Index of Stimulation were found in the Aszú wines of Tokaj reflecting their 5–6 „baskets” types, which characterized their „Botrytis related qualities”. Three categories of Aszú wines could be created on the basis of the Index of Stimulation. The stimulating effect was also proven by pure Botrytis cinerea particles owning peroxidase activity on the cytochrome c plus hydrogen peroxide reaction. The Botrytis influences and gluconic acid concentrations correlated positively. The augmentation of chemiluminescence in the cytochrome c plus hydrogen peroxide reaction could characterize the peroxidase activity of various wines and, furthermore, the „Botrytis cinerea related quality” of various Botrytis wines. However, this quality did not reflect completely the values of flavour and odour in these wines.
... Biofotonika rozwija się dynamicznie w kilku różnych kierunkach co jest związane z jej licznymi i silnymi korelacjami z różnymi dyscyplinami naukowymi [1]. Kwantowe techniki informacyjne związane są z biofotoniką od niedawna na kilku różnych poziomach badawczych oraz aplikacyjnych. ...
... Rolnictwo inteligentne i intensywne wymaga nowych technik monitoringu i zarządzania. W interdyscyplinarny obszar możliwości aplikacji biofotoniki w tym zakresie wchodzą, np.: monitorowanie równomierności nawożenia, ocena jakości gleby, obserwacja prawidłowości wegetacji, detekcja patogenów i toksyn, [1] itp. W wymienianych tutaj kierunkach rozwoju biofotoniki istotą jest zarówno zrozumienie wykorzystywanego nowego zjawiska na poziomie podstawowym, jak opracowanie jego funkcjonalizacji na poziomie laboratoryjnym, prowadzenie cyklu badań aplikacyjnych nowej metody, być może badań przedklinicznych, a następnie być może funkcjonalizacja na poziomie instrumentalnym i w końcu być może także komercyjnym. ...
Article
Full-text available
Biophotonics is an area at the intersection of life and light sciences. Compared to other areas, it is a relatively new discipline. It covers the use of light as an energy source enabling basic research and development of applications in biological, pharmaceutical, environmental, agricultural and medical sciences. The term biophotonics and its currently broad thematic approach has been used relatively recently, but still for several decades. The combination of the light and the biology is much older. Many significant milestones in its early and recent developments can be listed, starting with the simplest microscopy techniques, focused beam phototherapy, and then the discovery and development of the green fluorescent protein, the development of super-resolution fluorescence microscopy, optical tweezers and their applications in biology, broadband spectroscopic techniques in the UV-VIS-IR-MIR spectrum, pulse oximetry and other optical diagnostic techniques, various imaging methods, including optical coherence tomography. Biophotonics is the development of diagnostic and therapeutic techniques in dermatology, ophthalmology - treatment of diabetic retinopathy, photodynamic therapy and its development in the field of photoimmunotherapy. Techniques of neuromodulation and optical nanomanipulation include optogenetics and non-genetic methods of photostimulation. Biophotonics includes nanomachines/molecular nanorobots powered and controlled by light. Biophotonics is correlated with photobiology, biomedical physics and engineering, photo-electro- -biochemistry, as well as with quantum information techniques, e.g. through techniques such as ghost-imaging or drug discovery. Biophotonics to complex laboratory, biomedical but also industrial equipment.
... At the tissue and organism level, integrated molecular optical imaging techniques are being developed for the optical diagnosis of tissues and organisms. These techniques add to standardized medical clinical imaging [5]. ...
Article
Full-text available
This article discusses four fields of study with the potential to revolutionize our understanding and interaction with biological systems: quantum biophotonics, molecular and supramolecular bioelectronics, quantum-based approaches in gaming, and nano-biophotonics. Quantum biophotonics uses photonics, biochemistry, biophysics, and quantum information technologies to study biological systems at the sub-nanoscale level. Molecular and supramolecular bioelectronics aim to develop biosensors for medical diagnosis, environmental monitoring, and food safety by designing materials and devices that interface with biological systems at the molecular level. Quantum-based approaches in gaming improve modeling of complex systems, while nanomedicine enhances disease diagnosis, treatment, and prevention using nanoscale devices and sensors developed with quantum biophotonics. Lastly, nano-biophotonics studies cellular structures and functions with unprecedented resolution.
Article
Full-text available
Nanomaterials-based phototherapies, mainly including photothermal therapy (PTT), photodynamic therapy (PDT) and photoimmunotherapy (PIT), present high efficacy, minimal invasion and negligible adverse effects in cancer treatment. The integrated phototherapeutic modalities can enhance the efficiency of cancer immunotherapy for clinical application transformation. The near-infrared (NIR) light source enables phototherapies with the high penetration depth in the biological tissues, less toxic to normal cells and tissues and a low dose of light irradiation. Mediated via the novel NIR-responsive nanomaterials, PTT and PDT are able to provoke cancer cells apoptosis from the generated heat and reactive oxygen species, respectively. The released cancer-specific antigens and membrane damage danger signals from the damaged cancer cells trigger immune responses, which would enhance the antitumor efficacy via a variety of immunotherapy. This review summarized the recent advances in NIR-triggered photo-/immune-therapeutic modalities and their synergistic mechanisms and applications toward cancers. Furthermore, the challenges, potential solutions and future directions of NIR-triggered photo-/immunotherapy were briefly discussed.
Article
Full-text available
Optically controlled nongenetic neuromodulation represents a promising approach for the fundamental study of neural circuits and the clinical treatment of neurological disorders. Among the existing material candidates that can transduce light energy into biologically relevant cues, silicon (Si) is particularly advantageous due to its highly tunable electrical and optical properties, ease of fabrication into multiple forms, ability to absorb a broad spectrum of light, and biocompatibility. This protocol describes a rational design principle for Si-based structures, general procedures for material synthesis and device fabrication, a universal method for evaluating material photoresponses, detailed illustrations of all instrumentation used, and demonstrations of optically controlled nongenetic modulation of cellular calcium dynamics, neuronal excitability, neurotransmitter release from mouse brain slices, and brain activity in the mouse brain in vivo using the aforementioned Si materials. The entire procedure takes ~4–8 d in the hands of an experienced graduate student, depending on the specific biological targets. We anticipate that our approach can also be adapted in the future to study other systems, such as cardiovascular tissues and microbial communities. © 2019, The Author(s), under exclusive licence to Springer Nature Limited.
Article
Full-text available
Fluorescence imaging is increasingly gaining intraoperative applications. Here, we highlight a few recent advances in the surgical use of fluorescent probes.
Article
Full-text available
A technique called optical coherence tomography (OCT) has been developed for noninvasive cross-sectional imaging in biological systems. OCT uses low-coherence interferometry to produce a two-dimensional image of optical scattering from internal tissue microstructures in a way that is analogous to ultrasonic pulse-echo imaging. OCT has longitudinal and lateral spatial resolutions of a few micrometers and can detect reflected signals as small as ~10-10 of the incident optical power. Tomographic imaging is demonstrated in vitro in the peripapillary area of the retina and in the coronary artery, two clinically relevant examples that are representative of transparent and turbid media, respectively.
Article
This Account is the first comprehensive review article on the newly developed, photochemistry-based cancer therapy near-infrared (NIR) photoimmunotherapy (PIT). NIR-PIT is a molecularly targeted phototherapy for cancer that is based on injecting a conjugate of a near-infrared, water-soluble, silicon-phthalocyanine derivative, IRdye700DX (IR700), and a monoclonal antibody (mAb) that targets an expressed antigen on the cancer cell surface. Subsequent local exposure to NIR light turns on this photochemical “death” switch, resulting in the rapid and highly selective immunogenic cell death (ICD) of targeted cancer cells. ICD occurs as early as 1 min after exposure to NIR light and results in irreversible morphologic changes only in target-expressing cells based on the newly discovered photoinduced ligand release reaction that induces physical changes on conjugated antibody/antigen complex resulting in functional damage on cell membrane. Meanwhile, immediately adjacent receptor-negative cells are totally unharmed. Because of its highly targeted nature, NIR-PIT carries few side effects and healing is rapid. Evaluation of the tumor microenvironment reveals that ICD induced by NIR-PIT results in rapid maturation of immature dendritic cells adjacent to dying cancer cells initiating a host anticancer immune response, resulting in repriming of polyclonal CD8⁺T cells against various released cancer antigens, which amplifies the therapeutic effect of NIR-PIT. NIR-PIT can target and treat virtually any cell surface antigens including cancer stem cell markers, that is, CD44 and CD133. A first-in-human phase 1/2 clinical trial of NIR-PIT using cetuximab-IR700 (RM1929) targeting EGFR in inoperable recurrent head and neck cancer patients successfully concluded in 2017 and led to “fast tracking” by the FDA and a phase 3 trial (https://clinicaltrials.gov/ct2/show/NCT03769506) that is currently underway in 3 countries in Asia, US/Canada, and 4 countries in EU. The next step for NIR-PIT is to further exploit the immune response. Preclinical research in animals with intact immune systems has shown that NIT-PIT targeting of immunosuppressor cells within the tumor, such as regulatory T-cells, can further enhance tumor-cell-selective systemic host-immunity leading to significant responses in distant metastatic tumors, which are not treated with light. By combining cancer-targeting NIR-PIT and immune-activating NIR-PIT or other cancer immunotherapies, NIR-PIT of a local tumor, could lead to responses in distant metastases and may also inhibit recurrences due to activation of systemic anticancer immunity and long-term immune memory without the systemic autoimmune adverse effects often associated with immune checkpoint inhibitors. Furthermore, NIR-PIT also enhances nanodrug delivery into tumors up to 24-fold superior to untreated tumors with conventional EPR effects by intensively damaging cancer cells behind tumor vessels. We conclude by describing future advances in this novel photochemical cancer therapy that are likely to further enhance the efficacy of NIR-PIT.
Article
Light-matter interactions can provide a wealth of detailed information about the structural, electronic, optical, and chemical properties of materials through various excitation and scattering processes that occur over different length, energy, and timescales. Unfortunately, the wavelike nature of light limits the achievable spatial resolution for interrogation and imaging of materials to roughly γ/2 because of diffraction. Scanning near-field optical microscopy (SNOM) breaks this diffraction limit by coupling light to nanostructures that are specifically designed to manipulate, enhance, and/or extract optical signals from very small regions of space. Progress in the SNOM field over the past 30 years has led to the development of many methods to optically characterize materials at lateral spatial resolutions well below 100 nm.Wereview these exciting developments and demonstrate how SNOMis truly extending optical imaging and spectroscopy to the nanoscale. Expected final online publication date for the Annual Review of Chemical and Biomolecular Engineering Volume 9 is June 7, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
Article
THE effect of the laser on the eye has been known since the work of Zaret1,2. The effect on the skin is not well known3,4. Previously, some physicists have reported subjectively no effects at all or only a slight pricking sensation of the skin2.
Article
Temporally precise, noninvasive control of activity in well-defined neuronal populations is a long-sought goal of systems neuroscience. We adapted for this purpose the naturally occurring algal protein Channelrhodopsin-2, a rapidly gated light-sensitive cation channel, by using lentiviral gene delivery in combination with high-speed optical switching to photostimulate mammalian neurons. We demonstrate reliable, millisecond-timescale control of neuronal spiking, as well as control of excitatory and inhibitory synaptic transmission. This technology allows the use of light to alter neural processing at the level of single spikes and synaptic events, yielding a widely applicable tool for neuroscientists and biomedical engineers.
Millisecond-timescale, Genetically Targeted Optical Control of Neural Activity
  • Boyden