Periodic Reporting for period 1 - InjectableLasers (Biocompatible and biodegradable microlasers that can be injected into the human body)
Reporting period: 2017-05-01 to 2019-04-30
The use of light in medicine is a very rapidly expanding area of research, with light being used in the treatment of skin diseases, imaging, surgery as well as brain-activity stimulation and recording. Currently, the only routinely used optical devices inside the human body are artificial intraocular lenses and fibre-optic devices or catheters. On the other hand, the direct integration of photonic components into living tissue would enhance the interaction of light with living matter and enable new applications in sensing and light generation. Potentially, almost any photonic device could be made out of biocompatible materials. I envision one day opening an optics product catalogue that includes a variety of implantable, biocompatible components and devices. The development of implantable photonic devices has implications for advancing biomedical imaging, diagnosis and therapy by opening up possibilities for prolonged sensing and diagnostics and more targeted treatments. The goal of InjectableLasers was to make, for the first time, biocompatible and biodegradable/resorbable microlasers, which could be injected into the human body. Specifically, the lasers support either whispering-gallery modes or Bragg modes (cholesterol laser). The gain material was composed of a non-toxic dye and the lasers were pumped by an external laser. Their operation was demonstrated both in cell cultures and inside skin tissue. A laser-like emission was also, for the first time, demonstrated using bioluminescence pumping without the use of an artificial light source.
Conclusions of the action
All the objectives of the action were achieved, and in some aspects surpassed, with minimal deviation from the plan. The main achievements include several world firsts: 1.) the first microlaser made completely out of substances approved for medical use, 2.) the first injectable laser, 3.) the first micron-sized biolaser operating within biological tissues, 3.) the first optical cavity pumped with bioluminescence and 4.) the first biocompatible Bragg microlaser. Therefore, the action was concluded very successfully.
Conclusions of the action
All the objectives of the action were achieved, and in some aspects surpassed, with minimal deviation from the plan. The main achievements include several world firsts: 1.) the first microlaser made completely out of substances approved for medical use, 2.) the first injectable laser, 3.) the first micron-sized biolaser operating within biological tissues, 3.) the first optical cavity pumped with bioluminescence and 4.) the first biocompatible Bragg microlaser. Therefore, the action was concluded very successfully.
Work performed and overview of the results
Biocompatible and biodegradable lasers in the form of solid microbeads and liquid microdroplets were demonstrated. The spherical lasers were fabricated from biocompatible materials that are already used for medical implants. The lasers were manufactured in the form of microspheres with sizes ranging from 10 µm to 25 µm containing a fluorescent dye, with all the materials approved for use in humans. The operation of these lasers was demonstrated inside the eye (cornea), skin tissue and blood. Microlasers are typically pumped by an external light source, which limits their ability to operate deep inside tissues. In InjectableLasers the microcavities were pumped using bioluminescence, for the first time, to generate a laser-like emission, without the use of any external light source. Bioluminescence is the generation of light in living organisms by the chemical reaction of luciferin (“fuel” that provides energy) and luciferase (the enzyme that catalyses the reaction). The main advantage of bioluminescence is that there is no need for an external source of light, thus ending the limit relating to light penetrating the tissue. A biocompatible Bragg onion laser was made out of cholesterols, which are naturally occurring in living organisms, making the laser naturally biocompatible and biodegradable. A mixture of cholesterols forms a liquid-crystal cholesteric phase, which has a periodic structure and therefore acts as a photonic crystal, selectively reflecting the light. The Bragg onion laser is a unique source of light, since it is single mode, coherent, the light radiates in all directions and therefore could be used for biomedical purposes as a source of light for imaging, sensing, therapy and holography. Furthermore, the emission wavelength from cholesteric liquid-crystal lasers is highly temperature dependent, so remote temperature sensing within biological tissue could be demonstrated.
Exploitation and dissemination
The results of the action were published in two peer-reviewed articles in the following journal articles: Optica and Optics express. The work has been also presented on 9 international invited conference talks including prestigious conferences such as Gordon Research Conference and SPIE Photonic West. Apart from invited talks, the work was presented at 5 talks at various local events, seminars, invited talks at universities and schools. The results of this action are very interesting to the general public. The fellow took part in 6 news items on radio, in newspapers and a half-hour science show about biolasers on national TV. He was sharing his work on Facebook and the laboratory website. There were also regular visits to his laboratory, including students as well as prominent scientists from all over the world.
Biocompatible and biodegradable lasers in the form of solid microbeads and liquid microdroplets were demonstrated. The spherical lasers were fabricated from biocompatible materials that are already used for medical implants. The lasers were manufactured in the form of microspheres with sizes ranging from 10 µm to 25 µm containing a fluorescent dye, with all the materials approved for use in humans. The operation of these lasers was demonstrated inside the eye (cornea), skin tissue and blood. Microlasers are typically pumped by an external light source, which limits their ability to operate deep inside tissues. In InjectableLasers the microcavities were pumped using bioluminescence, for the first time, to generate a laser-like emission, without the use of any external light source. Bioluminescence is the generation of light in living organisms by the chemical reaction of luciferin (“fuel” that provides energy) and luciferase (the enzyme that catalyses the reaction). The main advantage of bioluminescence is that there is no need for an external source of light, thus ending the limit relating to light penetrating the tissue. A biocompatible Bragg onion laser was made out of cholesterols, which are naturally occurring in living organisms, making the laser naturally biocompatible and biodegradable. A mixture of cholesterols forms a liquid-crystal cholesteric phase, which has a periodic structure and therefore acts as a photonic crystal, selectively reflecting the light. The Bragg onion laser is a unique source of light, since it is single mode, coherent, the light radiates in all directions and therefore could be used for biomedical purposes as a source of light for imaging, sensing, therapy and holography. Furthermore, the emission wavelength from cholesteric liquid-crystal lasers is highly temperature dependent, so remote temperature sensing within biological tissue could be demonstrated.
Exploitation and dissemination
The results of the action were published in two peer-reviewed articles in the following journal articles: Optica and Optics express. The work has been also presented on 9 international invited conference talks including prestigious conferences such as Gordon Research Conference and SPIE Photonic West. Apart from invited talks, the work was presented at 5 talks at various local events, seminars, invited talks at universities and schools. The results of this action are very interesting to the general public. The fellow took part in 6 news items on radio, in newspapers and a half-hour science show about biolasers on national TV. He was sharing his work on Facebook and the laboratory website. There were also regular visits to his laboratory, including students as well as prominent scientists from all over the world.
Progress beyond the state of the art
Prior to this investigation there was very limited research and only a few publications about biocompatible or natural lasers, examples being silk or hydrogel Bragg lasers or vitamin droplet lasers. Furthermore, all the lasers developed before had footprints of the order of millimetres, i.e. too large for injection and use in the human body. None of these lasers had been operated inside biological tissue or their biocompatibility and biodegradability had not been tested. InjectableLasers achieved all these goals.
Socio-economic impact and the wider societal implications
The lasers can act as very sensitive sensors, because the wavelength of the emitted line depends on their environment, thereby enabling us to better understand the cellular processes. For example, by using our lasers inside the cells, we measured the change in the refractive index – the way light travels through the cell – while varying the concentration of salt in the medium surrounding the cells. The refractive index is directly related to the concentration of chemical constituents within the cells, such as DNA, proteins and lipids.
Our new cell-laser technology will help in the understanding of cellular processes and improve medical diagnosis and therapies. They could eventually provide remote sensing inside the human body without the need for sample collection. The method could be particularly useful for the deep imaging of biological tissues. The unique emission from each laser can be used as a barcode to track and identify individual lasers, thereby enabling the study of cell migration and cancer metastasis. Cell lasers also hold promise as a way of delivering the laser for therapies, for example, to activate photosensitive drugs and to kill microbes or cancerous cells. These new medical procedures will have in long term positive benefits in terms of quality of life of European citizens.
Prior to this investigation there was very limited research and only a few publications about biocompatible or natural lasers, examples being silk or hydrogel Bragg lasers or vitamin droplet lasers. Furthermore, all the lasers developed before had footprints of the order of millimetres, i.e. too large for injection and use in the human body. None of these lasers had been operated inside biological tissue or their biocompatibility and biodegradability had not been tested. InjectableLasers achieved all these goals.
Socio-economic impact and the wider societal implications
The lasers can act as very sensitive sensors, because the wavelength of the emitted line depends on their environment, thereby enabling us to better understand the cellular processes. For example, by using our lasers inside the cells, we measured the change in the refractive index – the way light travels through the cell – while varying the concentration of salt in the medium surrounding the cells. The refractive index is directly related to the concentration of chemical constituents within the cells, such as DNA, proteins and lipids.
Our new cell-laser technology will help in the understanding of cellular processes and improve medical diagnosis and therapies. They could eventually provide remote sensing inside the human body without the need for sample collection. The method could be particularly useful for the deep imaging of biological tissues. The unique emission from each laser can be used as a barcode to track and identify individual lasers, thereby enabling the study of cell migration and cancer metastasis. Cell lasers also hold promise as a way of delivering the laser for therapies, for example, to activate photosensitive drugs and to kill microbes or cancerous cells. These new medical procedures will have in long term positive benefits in terms of quality of life of European citizens.