The rapid development of biophotonics and biomedical sciences makes a high demand on photonic structures to be interfaced with biological systems that are capable of manipulating light at small scales for sensitive detection of biological signals and precise imaging of cellular structures. However, conventional photonic structures based on artificial materials (either inorganic or toxic organic) inevitably show incompatibility and invasiveness when interfacing with biological systems.
The design of biophotonic probes from the abundant natural materials, particularly biological entities such as virus, cells and tissues, with the capability of multifunctional light manipulation at target sites greatly increases the biocompatibility and minimizes the invasiveness to biological microenvironment. In this review, advances in biophotonic probes for bio-detection and imaging are reviewed. We emphatically and systematically describe biological entities-based photonic probes that offer appropriate optical properties, biocompatibility, and biodegradability with different optical functions from light generation, to light transportation and light modulation.
Three representative biophotonic probes, i.e., biological lasers, cell-based biophotonic waveguides and bio-microlenses, are reviewed with applications for bio-detection and imaging. Finally, perspectives on future opportunities and potential improvements of biophotonic probes are also provided.Sensitive detection of biological signals and precise observation of pathological changes are of great importance for the early diagnosis and treatment of infectious diseases, cancer, and other health disorders. However, owing to the low quantity of biochemical signals and complex microenvironment in biological systems, the detection of the targets of interest is challenging. Fortunately, the prosperous development of optical and photonic technologies in recent years provides many choices for optical detection and imaging, holding great promises for real-time visualization of biological signals in complex biological structures and processes.
Optical detection exploits optical responses, such as light absorption, scattering, fluorescence, and reflectance, induced by biophysical/biochemical changes for bio-identification and disease diagnosis3. Due to the inherently label-free nature, optical detection is a powerful alternative to conventional detection techniques (e.g., mass or electrochemical)With optical detection techniques, real-time signals of a wide range of biological test samples (from molecular biomarkers to pathogens and cells, and even to tissues and organs) can be obtained in a non-invasive manner with high-sensitivity and high-resolution To date, optical detection and imaging have been demonstrated to be one of the most powerful technologies for detection of biological signals and for diagnosis .
For a precise and flexible optical detection in a biological microenvironment, photonic probes with micro/nanostructures are always desirable. For this purpose, the selection of appropriate optical materials is certainly crucial, since the probing performance largely depends on their chemical and mechanical properties, optical functionalities as well as biological performances.
To date, the most commonly used materials for the assembly of versatile photonic components and photonic probes are mainly based on inorganic materials such as silica glass, or organic polymers such as polymer nanowires. Because of their excellent optical properties, such as high transparency and suitable mechanical strength, these materials have been applied for nanophotonic integrated devices in diversified fields of application. For example, optical waveguides based on silica optical fibers have been widely studied and were even used for implantations in animal bodies, particularly fiber-optic implants in the brain for optogenetic studies.
However, the main disadvantage of these photonic components based on traditional materials is low biocompatibility and biodegradability, which greatly limit their potential in biomedical applications. High biocompatibility of a material is a fundamental requirement for in vivo applications, which demands the absence of toxicity and low health threat to the living systems29. Moreover, high biocompatibility also refers to the biofunctionalities that the implants can perform their expected functions in vivo. Additionally, biodegradability is another essential requirement, since the materials can be degraded and metabolized by the body without the need for additional operations to remove the implants.
With abundant natural biomaterials and biological entities, Mother Nature always inspire us to design photonic structures and probes to manipulate light. Indeed, living cells and microscopic organisms as well as their derivates such as DNA, proteins, silk and cellulose et al., show different capabilities to interact with light, and can further serve as different photonics devices such as waveguides, microlenses, gratings, and even lasers. These natural biomaterials and biological entities hold huge promise for creation of new photonic probes for bio-detection, imaging, and therapeutic applications.
They inherently possess excellent biological performances, including noninvasiveness, high biocompatibility, biodegradability, and resorbability. Moreover, another interesting feature of biological entities such as virus, cells and tissues is their ability to serve simultaneously as optical devices and diagnostic specimen, which facilitate further real-time detection and imaging in biocompatible microenvironments.
Therefore, instead of bio-derived materials and biomolecules (such as proteins and nucleic acids), biophotonic probes introduced in this review are mainly focused on large biological entities, such as virus, bacteria, fungi, algae, mammalian cells and tissues. By translating biological principles into man-made designs, these biophotonic probes offer a seamless interface between optical and biological worlds.
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