Biophotonics--the science of generating, transmitting, and detecting photons that interact with tissue or biomolecules--has come a long way in recent years. That's fine, you may say, but why should biologists, biotechnologists, and bioengineers take the time to understand what it is and how they may use this technology? Well, biophotonics has the potential to provide the enabling technologies for significant advances in medical diagnostics, therapeutics, and biotechnology by exploiting light absorption and reemission, as well as elastic and inelastic photon scattering events in tissues or samples. Plus, there are a growing number of jobs available.

A large number of start-up companies entering the biotechnology sector have their scientific roots in the chemistry, immunology, and molecular biology laboratories of various North American universities. The chief scientific officers usually have an excellent handle on the chemistry involved in detecting physiologically relevant levels of proteins or gene mutations. The business plans call for a focused research plan related to the chemistry using typical laboratory equipments.

But little attention is often paid to the all-important final step--detecting the final product. Scientists tend to resort to the relatively cost-effective and efficient techniques of 'fluorescence' or 'optics' for the detection of whatever is of interest to them. The revolutionary technique of biophotonics can potentially help companies avoid significant delays in product development, usually at a time when the capital burn rate is already high.

Photons can be very useful things for medical applications: Photons can travel through tissues, probing the tissue through various light-tissue interactions and eventually carrying the information back to the tissue surface for subsequent optoelectronic detection. Hence, the science of biophotonics is finding numerous applications within medicine and research.

Diagnostics

Laser-induced fluorescence is an active field of research in Canada and worldwide. It is used for early detection of cancer in the gastrointestinal track and the lung. These and other body cavities are accessible via flexible endoscopes enabling the delivery of excitation light, commonly blue light, to the tissue and collecting the emitted fluorescent light, usually in the green and red wavelength band, by fiber bundles for imaging outside of the body. Normal tissue can be differentiated from precancerous and cancerous sites based on the emitted spectrum or colour of the light, where the latter sites emit less light overall and preferentially at longer wavelength, e.g., in the red part of the spectrum. The differences in the emission spectra are due to changes in the anatomy and presence of different fluorescing biomolecules. Hence, physicians have not only shape as their main feature to identify suspicious sites for biopsy, but also color. The latter is very important for early lesions when the abnormal tissue is not raised over the surrounding normal tissue.

Therapeutics

Photodynamic therapy has been approved as a new cancer treatment modality for various early cancers and for palliative care. It is based on the systemic administration of a nontoxic drug, called a photosensitizer, which preferentially localizes to the tumour cells. Red light provided by a laser is directed onto the tumour tissue and, when absorbed by the photosensitizer, results in the production of short-lived toxic components that cannot spread beyond the illuminated volume. Hence, selectivity is provided not only by the pharmacokinetics of the photosensitizer but also by the dosimetry of the activation light, practically eliminating the systemic toxicity. Clinical use of photodynamic therapy is currently available for the GI tract, lung, brain, prostate, and skin, to name but a few. Research is heavily centered on the development of new, more efficient drugs that can be activated by a far red or near infrared wavelength in order to increase the volumes that can be treated by surface illumination.

Biotechnology

While modern biotechnology is based on knowledge of molecular biology, determination or quantification of the DNA, mRNA, or protein content relies on optical methods to extract the information, predominantly through the use of fluorescent-labelled antibodies or similar labels. This is evident in flow cytometry, confocal fluorescence microscopy, or the all-too-well-known GeneChips. One of the limitations facing standard optical techniques in molecular biology and biotechnology is that only a limited number of chemical species can be monitored and quantified in a given sample. Through the use of better wavelength selectivity on the source and detection side, the number of monitored species can be increased by a factor of 10 or more. The ultimate goal is a system that enables determination of the entire genetic content (DNA), the translated portion (mRNA), or the transcribed material (proteins) from a given sample or population. This technology could undoubtedly speed up the process of getting a product into the marketplace.

The Future for R&D

The use of photons in therapeutic, diagnostic, and biotechnology applications will expand tremendously in the upcoming decade. An increasing number of large optical and optoelectronics companies are jumping on the biophotonics wagon, such as Motorola, who just created their own bioengineering and optics division, and Quadralogic Technologies of Vancouver, currently rated the 12th largest biotech company worldwide. Biotech companies that either collaborate with photonics companies, or have in-house photonics or optical engineering expertise, are most certainly better situated for success.

The full extent of the industrial R&D in biophotonics is difficult to assess as start-up companies usually protect their IP during the early phases of development. However, biophotonics companies are represented in all four optics industries clusters in Canada (Vancouver, South Western Ontario, Ottawa, and Quebec City). Additionally, the Institute Nacional Optique in Quebec and Photonics Research Ontario in Ontario have active research and industry support programs for R&D in biophotonics. The Canadian Institute for Photonics Innovation, a federal center of excellence, directs about 30% of its activities toward biophotonics research.

The breakthrough of biophotonics application in biotech and medicine is currently limited by two factors, namely the lack of awareness among start-up CEOs that biophotonics can play an important part in the development of new products and the current shortage of technicians, technologists, and scientists with a multidisciplinary education--a shortage that will most likely persist in the next few years. Biophotonics demands expertise from a wide variety of disciplines, and scientists will often have a physics, engineering, and optics background but at the same time possess knowledge about laser-tissue interactions and good general knowledge of biology, anatomy, and physiology. Biologists and physiologists with a broad level of interdisciplinary experience and know-how will also be in demand in this field. Biophotonics research may still be in its infancy, but the potential demand for the technology and qualified researchers is huge.

* Lothar Lilge is director of the Biophotonics Facility at Photonics Research Ontario and an assistant professor in the department of medical biophysics at the University of Toronto.