Since Theodore Maiman demonstrated the first laser a half century ago, stimulated emission and lasing have made a tremendous impact on modern science and technology. Although lasers and the coherent light they emit are omnipresent today, lasing has remained a man-made phenomenon. Generation of laser light has so far relied on artificial or engineered optical gain materials, such as doped crystals, semiconductors, synthetic dyes, and purified gases; biological materials and living organisms have not been explored as gain materials for lasers. This project introduces fluorescent proteins as a new optical gain material. The proposed research will investigate the optical amplification characteristics of biologically produced, biocompatible and biodegradable fluorescent proteins that have high quantum yield at various wavelengths across the entire visible spectrum. The fluorescent proteins offer unique properties not shared by any existing gain materials. For example, they can be expressed as functional transgene in a wide variety of organism.
Intellectual merit of this project is harnessing these properties of fluorescent proteins to demonstrate novel photonic device concepts, including protein lasers in solutions and in condensed-state forms, as well as biological lasers based on single cells expressing fluorescent proteins will be explored. Successful completion of the proposed research will improve our ability to control and optimize the stimulated emission properties of fluorescent proteins and demonstrate miniature lasers and amplifiers built on the biological platform. Furthermore, it is expected to provide insights into a range of novel protein-based devices and technologies for practical applications. For example, lasing within the tissues and inside the cells may offer new possibilities of nonlinear deep imaging and intracellular sensing for bioengineering and medical diagnosis. The ability to generate laser light in vivo may enable new approaches in light-controlled therapy and drug activation.
Broader impacts of this project include the opportunity to educate and train graduate students and postdoctoral fellows in the highly vibrant and multidisciplinary environment at the Wellman Center for Photomedicine. Undergraduate students enrolled in the Wellman-HST Summer Institute for Biomedical Optics and other summer internship programs will be invited to participate in this project. The researchers and students will learn how to work across boundaries between disciplines through creativity and inspiration. In the long run, stimulated emission from fluorescent proteins has the potential to improve human health by enabling innovative approaches to disease diagnosis and light-based treatments.
Since Theodore Maiman demonstrated stimulated optical radiation 50 years ago, lasers have made a tremendous impact on modern science and technology. The generation of laser light has relied on artificial materials, and biological materials and living organisms have not been explored as gain materials for lasers. Green fluorescent protein (GFP) has become a powerful tool in biomedical science as a reporter protein and imaging tracer. Directed mutation of GFP and other fluorescent proteins derived from naturally occurring organisms yielded variants with improved maturation, brightness, and stability and with emission bands across the entire visible spectrum. Considering their excellent properties as fluorescent emitters, we postulated that fluorescent proteins are promising candidates for the gain medium of biological lasers. The overarching goal of this project was to develop novel photonic technologies based on fluorescent proteins as optical gain material. In this 3-year project, we explored several ideas to realize novel photonic devices and technologies, with three specific aims: (1) investigate optical amplification by fluorescent proteins, (2) develop solid-state protein-based devices, and (3) demonstrate single-cell lasers. We have achieved these objectives. Using fluorescent proteins in solution, we demonstrated protein lasers. With biological cells that were engineered to produce fluorescent proteins, we demonstrated "living" biological cell lasers. Using dried fluorescent protein we demonstrated very efficient optical amplification and laser generation. We also achieved laser action based on energy transfer between different types of fluorescent proteins. The biologically produced, biocompatible, and biodegradable fluorescent protein offers unique properties not shared by any existing gain materials. In addition to fluorescent proteins, we also explored other biomolecules as a novel gain medium and successfully demonstrated a vitamin laser. Furthermore, we demonstrated light-guiding hydrogels for effective fiber-optic communications to fluorescent cells and molecules in the body. The project resulted in several high-impact papers in scientific journals and plenary and invited talks in scientific conferences. This project introduced a new optical gain material to the scientific community. It enhanced our ability to control and optimize the stimulated emission properties of fluorescent proteins and demonstrated the feasibility of new protein-based photonic devices. We showed that miniature lasers and amplifiers built on the novel biological platform could enable a variety of applications, such as sensing, at the interface of physics and biology. This project allowed an opportunity to educate and train graduate students and postdoctoral fellows in the highly vibrant and multidisciplinary environment at the Wellman Center. Undergraduate students enrolled in the Harvard-MIT Summer Institute for Biomedical Optics and other summer internship programs participated in this project, learning how to work across boundaries between disciplines through creativity and inspiration. Some of the outcomes of this project were introduced to the general public through newspapers, general magazines, Internet interviews, and TV news.
