Biophotonic is an interdisciplinary field that covers the interaction between light (electromagnetic radiation) and biological materials such as subcellular structures, cells, tissues, and molecules in living organisms.
It holds potential to address important societal challenges, including in human health through the development of medical devices for the management of human diseases; in environmental health by enabling highly sensitive devices for advanced pollution detection; and in food and agriculture through providing means for assessing quality control and safety.
Within medicine and the life sciences, biophotonics promises progress and new developments with regard to a better understanding of the origins of disease, improving diagnosis and follow-up care, preventing disease, and treating patients individually and specifically (‘personalized medicine’). Advances in light-based technologies have resulted in innovative and transformative tools to study and manipulate biological systems at the subcellular, cellular, tissue, and organ levels. Optical devices are used in the clinic today to detect colon tumors, guide surgical excision, perform laser surgery, diagnose dermatological conditions, and far more.
Diagnostic biophotonics is used to detect diseases in their initial stages before actual medical symptoms occur in patients. By using optics, diagnostic biophotonics provides several advantages of sensing and imaging at the molecular level and also collects multidimensional data for evaluation. Technologies based on light are generally contact-free with less effect on integrity of living subjects and, consequently, can easily be applied in situ.
- Optical tagging: Proteins, cells, DNA, and tissues are tagged with optical tags and their incandescence or fluorescence is measured; also, according to the pathological or physiological situation the changes are analyzed.
- Visualization of complex structures: Advanced laser technology has enhanced imaging of vasculature retinal structures and other optic nerves to provide precise diagnosis of ocular diseases. By observing the modifications occurring in ocular capillaries, the diagnosis of common vascular disorders is enabled.
- Cellular level diagnosis: Sophisticated optical technologies involving lasers, and photonic and biophotonic applications in medicine provide assistance in observing and identifying cellular biochemistry and their functions, organ integrity, and the characteristics of tissues.
- Optical endoscopes: In medical applications, the combination of optical fibers and endoscopes is used for less invasive imaging and surgery of internal organs. Laser light with high-level intensity is delivered using an optical fiber to an inner region of the body, for instance, to eradicate tumors.
Applications of light include treatment of diseases by altering biological processes. Light is used for modifying the cellular functions photochemically and to remove tissues by photomechanical or photothermal process.
- Thermal contact: In this method, heat is produced by high-energy laser light, which is used to disrupt the tissues and, hence the main impact of laser light is photothermal. The response to laser light of the target tissue depends on the extent of increase in temperature and water content in that specific tissue.
- Bioimaging: This is noninvasive imaging technique that visualizes real-time biological processes. This technique aims at lowering the impact of cellular processes as much as possible. Through bio-imaging, the ion or metabolite levels of molecular processes are quantified. Latest developments in bio-imaging include fluorescence resonance energy transfer and two-photon fluorescence excitation microscopy. Images that are reconstructed in both 2D and 3D have enhanced the effective visualization of disease processes and models.
- Photobiostimulation: The process of activating live cells or organisms by laser radiation is known as biostimulation. Low intensity laser and light emitting diode are broadly used in various aspects by dermatologists, dentists, and surgeons. These laser radiations are low powered and do not generate heat that can disrupt biological tissues. They promote a curing effect by deep penetration into the tissues, enabling progression of the photochemical effect.
- Optical coherence tomography (OCT): This method can offer label-free high resolution optical imaging with higher sampling frequency of intraoperative evaluation. OCT is a fast developing technology with the ability to influence many fields of human biology and clinical medicine. It is analogous to ultrasound in which reflected light is detected instead of sound. It can be used in the functioning of optical biopsies by generating images that are similar to histological sections without any removal or blotting of tissues. OCT is used potentially in the study of various tumors and is also applied as intraoperative surgery in breast cancer.
Biophotonics is the science of producing and utilizing photons or light to image, identify, and engineer biological materials. It is the integration of four major technologies: biotechnology, lasers, photonics, and nanotechnology. Biomedical applications of biophotonics include light interactions in medicine and biology for the purposes of health care.
Advancements in a number of fields, including lasers, camera and imaging technology, advanced neural networks have shifted the center of technology innovation. Many companies have advancements in technology related to biophotonics.
The targets of interest occur in a complex environment, in which signal specificity and sensitivity are challenged to overcome background noise. These sensitivity limitations are being addressed in several ways. Detectors and detection systems are becoming more sensitive, enabling better signal collection with lower noise. The uniqueness of signal against biological background, separation of the signal from the noise, and data processing are also employed. Imaging speed is rapidly advancing, such as sweptsource OCT systems with MHz axial scan rates, requiring also the corresponding use of faster detectors.
Biophotonic imaging will reap enormous benefits from recent advances in machine- and deep-learning algorithms. Coupled with the computational power that is now available and the immense information content of images, deep-learning can reveal patterns in images and will couple with computer-aided-diagnosis to reveal patterns that are
otherwise not visualized.
Through the use of synthetic biology and discovery chemistry, brighter fluorescent and luminescent proteins, enzymes, and chemical probes are being created. The convergence of biophotonics with nanosciences and nanotechnologies is rapidly expanding the ability for highly multiplexed detection/imaging as, for example, in surface-enhanced Raman scattering (SERS) nanoparticles as well as periodic array-based substrates for SERS and surface-enhanced spectroscopies in general.
Nanotechnology has helped in the improvement of the sensing phenomenon by the use of nanomaterials ranging from nanocantilevers, nanowires, nanoparticles, nanorods, and nanotubes. Nanomaterials such as carbon nanotubes and indium oxide nanowires are widely used for the construction of nanobiosensors. The most promising nanobiosensors technology is said to be based on the electronic detection of the target molecule such as Field Effect Transistor (FET) nanosensor.
Scientists have invented an optical platform that will likely become the new standard in optical biointerfaces.
There is a growing and unfulfilled demand for optical systems for biomedical applications. Miniaturized and flexible optical tools are needed to enable reliable ambulatory and on-demand imaging and manipulation of biological events in the body. Integrated photonic technology has mainly evolved around developing devices for optical communications. The advent of silicon photonics was a turning point in bringing optical functionalities to the small form-factor of a chip.
Research in this field boomed in the past couple of decades. However, silicon is a dangerously rigid material for interacting with soft tissue in biomedical applications. This increases the risk for patients to undergo tissue damage and scarring, especially due to the undulation of soft tissue against the inflexible device caused by respiration and other processes.
Carnegie Mellon University’s Maysam Chamanzar and his team have invented an optical platform that will likely become the new standard in optical biointerfaces. He’s labeled this new field of optical technology “Parylene photonics,” demonstrated in a recent paper in Nature Microsystems and Nanoengineering. Chamanzar, an Assistant Professor of Electrical and Computer Engineering (ECE) and Biomedical Engineering, saw the pressing need for an optical platform tailored to biointerfaces with both optical capability and flexibility. His solution, Parylene photonics, is the first biocompatible and fully flexible integrated photonic platform ever made.
To create this new photonic material class, Chamanzar’s lab designed ultracompact optical waveguides by fabricating silicone (PDMS), an organic polymer with a low refractive index, around a core of Parylene C, a polymer with a much higher refractive index. The contrast in refractive index allows the waveguide to pipe light effectively, while the materials themselves remain extremely pliant. The result is a platform that is flexible, can operate over a broad spectrum of light, and is just 10 microns thick — about 1/10 the thickness of a human hair.
“We were using Parylene C as a biocompatible insulation coating for electrical implantable devices, when I noticed that this polymer is optically transparent. I became curious about its optical properties and did some basic measurements,” said Chamanzar. “I found that Parylene C has exceptional optical properties. This was the onset of thinking about Parylene photonics as a new research direction.”
Chamanzar’s design was created with neural stimulation in mind, allowing for targeted stimulation and monitoring of specific neurons within the brain. Crucial to this, is the creation of 45-degree embedded micromirrors. While prior optical biointerfaces have stimulated a large swath of the brain tissue beyond what could be measured, these micromirrors create a tight overlap between the volume being stimulated and the volume recorded. These micromirrors also enable integration of external light sources with the Parylene waveguides.
ECE alumna Maya Lassiter (MS, ’19), who was involved in the project, said, “Optical packaging is an interesting problem to solve because the best solutions need to be practical. We were able to package our Parylene photonic waveguides with discrete light sources using accessible packaging methods, to realize a compact device.”
The applications for Parylene photonics range far beyond optical neural stimulation, and could one day replace current technologies in virtually every area of optical biointerfaces. These tiny flexible optical devices can be inserted into the tissue for short-term imaging or manipulation. They can also be used as permanent implantable devices for long-term monitoring and therapeutic interventions.
Additionally, Chamanzar and his team are considering possible uses in wearables. Parylene photonic devices placed on the skin could be used to conform to difficult areas of the body and measure pulse rate, oxygen saturation, blood flow, cancer biomarkers, and other biometrics. As further options for optical therapeutics are explored, such as laser treatment for cancer cells, the applications for a more versatile optical biointerface will only continue to grow.
“The high index contrast between Parylene C and PDMS enables a low bend loss,” said ECE Ph.D. candidate Jay Reddy, who has been working on this project. “These devices retain 90% efficiency as they are tightly bent down to a radius of almost half a millimeter, conforming tightly to anatomical features such as the cochlea and nerve bundles.”
Another unconventional possibility for Parylene photonics is actually in communication links, bringing Chamanzar’s whole pursuit full circle. Current chip-to-chip interconnects usually use rather inflexible optical fibers, and any area in which flexibility is needed requires transferring the signals to the electrical domain, which significantly limits bandwidth. Flexible Parylene photonic cables, however, provide a promising high bandwidth solution that could replace both types of optical interconnects and enable advances in optical interconnect design.
“So far, we have demonstrated low-loss, fully flexible Parylene photonic waveguides with embedded micromirrors that enable input/output light coupling over a broad range of optical wavelengths,” said Chamanzar. “In the future, other optical devices such as microresonators and interferometers can also be implemented in this platform to enable a whole gamut of new applications.” With Chamanzar’s recent publication marking the debut of Parylene photonics, it’s impossible to say just how far reaching the effects of this technology could be. However, the implications of this work are more than likely to mark a new chapter in the development of optical biointerfaces, similar to what silicon photonics enabled in optical communications and processing.
Researchers define new law in laser physics via pulsation
Scientists at the University of Sydney Institute of Photonics and Optical Science developed a type of laser that can deliver high amounts of energy in short bursts, with potential applications in eye and heart surgery or the engineering of delicate materials. “This laser has the property that as its pulse duration decreases to less than a trillionth of a second, its energy could go through the roof,” said Martijn de Sterke, the director of the institute. “This makes them ideal candidates for the processing of materials that require short, powerful pulses. One application could be in corneal surgery, which relies on gently removing material from the eye. This requires strong, short light pulses that do not heat and damage the surface.”
The scientists said that to achieve their high-energy laser pulses, they looked into metrology and spectroscopy lasers, which use an effect known as soliton waves, which are waves of light that maintain their shape over long distances. “The fact that soliton waves in light maintain their shape means they are excellent for a wide range of applications, including telecommunications and spectrometry,” said lead author Antoine Runge from the university’s School of Physics. “However, while lasers producing these solitons are simple to make, they do not pack much punch. A completely different and expensive physical system is required to produce the high-energy optical pulses used in manufacturing.”
Co-author Andrea Blanco-Redondo, head of Silicon Photonics at Nokia Bell Labs, said, “Soliton lasers are the most simple, cost-effective, and robust way to achieve these short bursts. However, until now, conventional soliton lasers could not deliver enough energy.” She said, “Our results have the potential to make soliton lasers useful for biomedical applications.” In a typically applied soliton laser, the energy of light is inversely proportional to its pulse duration, demonstrated by the equation E = 1/τ. If you halve the pulse time, you get twice the amount of energy.
Using quartic solitons, the energy of light is inversely proportional to the third power of the pulse duration, or E = 1/τ3. This means that if your pulse time is halved, the energy it delivers in that time is multiplied by a factor of eight. “It is this demonstration of a new law in laser physics that is most important in our research,” Runge said. “We have shown that E = 1/τ3 and we hope this will change how lasers can be applied in the future.” Establishing this proof of principle will enable the team to make more powerful soliton lasers.
“In this research, we produced pulses that are as short as a trillionth of a second, but we have plans to get much shorter than that,” Blanco-Redondo said. “Our next goal is to produce femtosecond duration pulses — one quadrillionth of a second. This will mean ultrashort laser pulses with hundreds of kilowatts of peak power.” De Sterke said, “We hope this type of laser can open a new way to apply laser light when we need high peak energy but where the base material is not damaged.”
Lattice light-sheet microscopy tool supports 4D data analysis
Researchers at the University of Chicago designed a multidimensional imaging analysis pipeline for lattice light-sheet microscopy (LLSM). They set out to study T-cell function using high-dimensional microscopy, but then identified the need for an effective method of analysis. Because of limited data points for LLSM, the researchers needed an effective way to analyze the data in 4D. To increase the number of data points and allow for more sophisticated analyses, researchers Jillian Rosenberg and Guoshuai Cao developed a way to treat each molecule, rather than each cell, as a data point.
They developed a pipeline composed of publicly available software packages, called LLSM multidimensional analyses (LaMDA). The LaMDA pipeline combines high spatiotemporal resolution, 4D LLSM, machine learning, and dimensionality reduction to analyze T-cell receptor dynamics and predict T-cell signaling states without the need for complex biochemical measurements. The researchers used LaMDA to analyze images of T-cell receptor microclusters on the surface of live primary T cells under resting and stimulated conditions. They observed global spatial and temporal changes of T-cell receptors across the 3D cell surface, differentiated stimulated cells from unstimulated cells, predicted attenuated T-cell signaling after CD4 and CD28 receptor blockades, and reliably discriminated between structurally similar T-cell receptor ligands.
In addition to helping to expand scientists’ knowledge of T-cell biology, LaMDA could be used for drug testing and vaccine development. According to Rosenberg, one of the most promising aspects of LaMDA is its potential to predict biological responses without the need for complex experiments. “Researchers or pharmaceutical companies could use LaMDA to determine how certain drugs are resulting in subtle changes in subcellular signaling, which provides information on both drug safety and efficacy,” she said. “Our LaMDA pipeline could also be extended to the development of peptide vaccines to treat infection, cancer, and autoimmunity, or be used to study thymic education or peripheral tolerance, two very important topics in T-cell biology.”
The researchers validated LaMDA as an effective analysis pipeline that could be expanded to other fields of study. They designed LaMDA to be easy for other scientists to use, including those who may be unfamiliar with data science techniques. “We believe this analysis pipeline will benefit users of high-dimensional microscopy across all fields of science,” Cao said.
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