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Schematic design of the Brillouin fibre probe and potential applications. A) The Brillouin fibre probe can be integrated with existing technologies or serve as a novel solution for a wide range of applications. B) Schematics of a flexible, fibre-based Brillouin system. The inset shows a hollow core fibre and a system of miniaturised lenses to enable remote, contact-free measurements.
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Brillouin imaging (BI) has become a valuable tool for micromechanical material characterisation, thanks to extensive progress in instrumentation in the last few decades. This powerful technique is contactless and label-free, thus making it especially suitable for biomedical applications. Nonetheless, to fully harness the non-contact and non-destruc...
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... For a compact solution, the implementation of a fiber-based endoscopic imaging probe would be more preferable. The probe can be fabricated using a hollow core fiber [31,32] or two different fibers for illumination and scattered light collection [33]. ...
Biomechanical testing of human skin in vivo is important to study the aging process and pathological conditions such as skin cancer. Brillouin microscopy allows the all-optical, non-contact visualization of the mechanical properties of cells and tissues over space. Here, we use the combination of Brillouin microscopy and optical coherence tomography for motion-corrected, depth-resolved biomechanical testing of human skin in vivo. We obtained two peaks in the Brillouin spectra for the epidermis, the first at 7 GHz and the second near 9-10 GHz. The experimentally measured Brillouin frequency shift of the dermis is lower compared to the epidermis and is 6.8 GHz, indicating the lower stiffness of the dermis.
... When it comes to Brillouin microscopy and imaging, the work on photonic integration has only started with first demonstrations of Brillouin fiber probes reported in the last 5 years. 312,313 Harnessing evanescent field coupling to Brillouin modes using nano-waveguides offers new ways for sensing the surroundings and microscopy. 314 In addition to further progress in integrated photonic waveguides designs and integration of Brillouin-active waveguides with other onchip components, there are novel demonstrations of Brillouin scattering in optical fibers. ...
The Year 2022 marks 100 years since Leon Brillouin predicted and theoretically described the interaction of optical waves with acoustic waves in a medium. Accordingly, this resonant multi-wave interaction is referred to as Brillouin scattering. Today, Brillouin scattering has found a multitude of applications, ranging from microscopy of biological tissue, remote sensing over many kilometers, and signal processing in compact photonic integrated circuits smaller than the size of a thumbnail. What allows Brillouin scattering to be harnessed over such different length scales and research domains are its unique underlying properties, namely, its narrow linewidth in the MHz range, a frequency shift in the GHz range, large frequency selective gain or loss, frequency tunability, and optical reconfigurability. Brillouin scattering is also a ubiquitous effect that can be observed in many different media, such as freely propagating in gases and liquids, as well as over long lengths of low-loss optical glass fibers or short semiconductor waveguides. A recent trend of Brillouin research focuses on micro-structured waveguides and integrated photonic platforms. The reduction in the size of waveguides allows tailoring the overlap between the optical and acoustic waves and promises many novel applications in a compact footprint. In this review article, we give an overview of the evolution and development of the field of Brillouin scattering over the last one hundred years toward current lines of active research. We provide the reader with a perspective of recent trends and challenges that demand further research efforts and give an outlook toward the future of this exciting and diverse research field.
... However, the discussion of phototoxicity and other constraints have to be taken into account, see the chapters 4 and 5. Employing adaptive optical approaches [31][32][33] could further extent the applicabity of the system to scattering environments. Furthermore, fiber technology can enable minimally invasive Brillouin endomicroscopy [34][35][36]. With the adequate choice of the excitation parameters, ISBS promises to achieve high-speed mapping of viscoelastic properties of biological samples. ...
The impulsive stimulated Brillouin microscopy promises fast, non-contact measurements of the elastic properties of biological samples. The used pump-probe approach employs an ultra-short pulse laser and a cw laser to generate Brillouin signals. Modeling of the microscopy technique has already been carried out partially, but not for biomedical applications. The nonlinear relationship between pulse energy and Brillouin signal amplitude is proven with both simulations and experiments. Tayloring of the excitation parameters on the biologically relevant polyacrylamide hydrogels outline sub-ms temporal resolutions at a relative precision of <1%. Brillouin microscopy using the impulsive stimulated scattering therefore exhibits high potential for the measurements of viscoelastic properties of cells and tissues.
... Among all bioinks, methacrylate-based bioinks are most commonly used by users of Cellink bioprinters [89][90][91][92][93][94][95][96]. Cellink methacrylate-based bioinks are photo-crosslinking hydrogels prepared by the chemical addition of methacrylate groups in FDA-approved biomaterials, such as gelatin, collagen, hyaluronic acid, etc. ...
3D bioprinting is an advanced additive manufacturing approach evolved from traditional 3D printing to fulfill specific requirements for the applications of tissue engineering and regenerative medicine. During the past decade, bioprinting has progressed substantially showing its extraordinary potential for applications in different biomedical fields, however, a huge gap still exists for the large-scale industrialization and commercialization of this technology. In this review article, we will first discuss several successful bioprinting companies and their current efforts on the commercialization of bioprinting technology. Then future challenges that restrict the application of bioprinting will be discussed. Finally, we will conclude several key factors, which inhibit the translational development of bioprinting, while should be addressed soon.
... There are some technical problems in using optical fibers but they can be overcome at least partially, allowing for the obtainment of reliable measurements in simple liquids. In fact, a fiber optic Brillouin probe has been recently developed that is free of background signals and has state-of-the-art spectral resolution [40]. It is the first step to a "Brillouin endoscope". ...
... If future technological advances allow similar coupling of Brillouin and Raman spectroscopies at smaller scales, a similar analysis could become available for in vivo diagnosis. This advance should be possible using miniature endoscopic probes that are currently available for Raman and Brilluoin independently or in situ evaluation of biopsies by Brillouin-Raman coupled hypodermic needles for assessment of critical injection sites [39,40,[123][124][125]. ...
Brillouin spectroscopy has recently gained considerable interest within the biomedical field as an innovative tool to study mechanical properties in biology. The Brillouin effect is based on the inelastic scattering of photons caused by their interaction with thermodynamically driven acoustic modes or phonons and it is highly dependent on the material’s elasticity. Therefore, Brillouin is a contactless, label-free optic approach to elastic and viscoelastic analysis that has enabled unprecedented analysis of ex vivo and in vivo mechanical behavior of several tissues with a micrometric resolution, paving the way to a promising future in clinical diagnosis. Here, we comprehensively review the different studies of this fast-moving field that have been performed up to date to provide a quick guide of the current literature. In addition, we offer a general view of Brillouin’s biomedical potential to encourage its further development to reach its implementation as a feasible, cost-effective pathology diagnostic tool.
... Non-contact and label-free nature of both Brillouin and Raman microscopy suggests that these technologies can be translated to in vivo imaging scenarios to harness their full potential [34][35][36]. Recent developments have also shown the possibility of fibre integration of Brillouin systems [37]. Thus in the future, it would be possible to integrate Brillouin fibre probe within a bioprinter nozzle to achieve simultaneous fabrication and characterisation of bioprinted scaffolds and cell models. ...
Three-dimensional (3D) bioprinting has revolutionised the field of biofabrication by delivering precise, cost-effective and a relatively simple way of engineering in vitro living systems in high volume for use in tissue regeneration, biological modelling, drug testing and cell-based diagnostics. The complexity of modern bioprinted systems requires quality control assessment to ensure the resulting product meets the desired criteria of structural design, micromechanical performance and long-term durability. Brillouin microscopy could be an excellent solution for micromechanical assessment of the bioprinted models during or post-fabrication since this technology is non-destructive, label-free and is capable of microscale 3D imaging. In this work, we demonstrate the application of Brillouin microscopy to 3D imaging of hydrogel microstructures created through drop-on-demand bioprinting. In addition, we show that this technology can resolve variations between mechanical properties of the gels with slightly different polymer fractions. This work confirms that Brillouin microscopy can be seen as a characterisation technology complementary to bioprinting, and in the future can be combined within the printer design to achieve simultaneous real-time fabrication and micromechanical characterisation of in vitro biological systems.
... Noncontact and label-free nature of both Brillouin and Raman microscopy suggests that these technologies can be translated to in vivo imaging scenarios to harness their full potential [29][30][31]. Recent developments have also shown the possibility of fibre integration of Brillouin systems [32]. Thus in the future, it would be possible to integrate Brillouin fibre probe within a bioprinter nozzle to achieve simultaneous fabrication and characterisation of bioprinted scaffolds and cell models. ...
Three-dimensional (3D) bioprinting has revolutionised the field of biofabrication by delivering precise, cost-effective and a relatively simple way of engineering in vitro living systems in high volume for use in tissue regeneration, biological modelling, drug testing and cell-based diagnostics. The complexity of modern bioprinted systems requires quality control assessment to ensure the resulting product meets the desired criteria of structural design, micromechanical performance and long-term durability. Brillouin microscopy could be an excellent solution for micromechanical assessment of the bioprinted models during or post-fabrication since this technology is non-destructive, label-free and is capable of microscale 3D imaging. In this work, we demonstrate the application of Brillouin microscopy to 3D imaging of hydrogel microstructures created through drop-on-demand bioprinting. In addition, we show that this technology can resolve variations between mechanical properties of the gels with slightly different polymer fractions. This work confirms that Brillouin microscopy can be seen as a characterisation technology complementary to bioprinting, and in the future can be combined within the printer design to achieve simultaneous real-time fabrication and micromechanical characterisation of in vitro biological systems.
Brillouin Light Scattering (BLS) spectroscopy is a non-invasive, non-contact, label-free optical technique that can provide information on the mechanical properties of a material on the sub-micron scale. Over the last decade it has seen increased applications in the life sciences, driven by the observed significance of mechanical properties in biological processes, the realization of more sensitive BLS spectrometers and its extension to an imaging modality. As with other spectroscopic techniques, BLS measurements not only detect signals characteristic of the investigated sample, but also of the experimental apparatus, and can be significantly affected by measurement conditions. The aim of this consensus statement is to improve the comparability of BLS studies by providing reporting recommendations for the measured parameters and detailing common artifacts. Given that most BLS studies of biological matter are still at proof-of-concept stages and use different--often self-built--spectrometers, a consensus statement is particularly timely to assure unified advancement.
This report presents an optical fibre-based endo-microscopic imaging tool that simultaneously measures the topographic profile and 3D viscoelastic properties of biological specimens through the phenomenon of time-resolved Brillouin scattering. This uses the intrinsic viscoelasticity of the specimen as a contrast mechanism without fluorescent tags or photoacoustic contrast mechanisms. We demonstrate 2 μm lateral resolution and 320 nm axial resolution for the 3D imaging of biological cells and Caenorhabditis elegans larvae. This has enabled the first ever 3D stiffness imaging and characterisation of the C. elegans larva cuticle in-situ. A label-free, subcellular resolution, and endoscopic compatible technique that reveals structural biologically-relevant material properties of tissue could pave the way toward in-vivo elasticity-based diagnostics down to the single cell level.