SignificanceExtending the photoacoustic microscopy (PAM) into the mid-infrared (MIR) molecular fingerprint region constitutes a promising route toward label-free imaging of biological molecular structures. Realizing this objective requires a high-energy nanosecond MIR laser source. However, existing MIR laser technologies are limited to either low pulse energy or free-space structure that is sensitive to environmental conditions. Fiber lasers are promising technologies for PAM for their potential to offer both high pulse energy and robust performance, which however have not yet been used for PAM because it is still at the infant research stage.AimWe aim to employ the emerging gas-filled anti-resonant hollow-core fiber (ARHCF) laser technology for MIR-PAM for the purpose of imaging myelin-rich regions in a mouse brain.ApproachThis laser source is developed with a high-pulse-energy nanosecond laser at 3.4μm, targeting the main absorption band of myelin sheaths, the primary chemical component of axons in the central nervous system. The laser mechanism relies on two-order gas-induced vibrational stimulated Raman scattering for non-linear wavelength conversion, starting from a 1060-nm pump laser to 3.4 μm through the two-stage gas-filled ARHCFs.ResultsThe developed fiber Raman laser was used for the first time for MIR-PAM of mouse brain regions containing structures rich in myelin. The high peak power of ∼1.38 kW and robust performance of the generated MIR Raman pulse addressed the challenge faced by the commonly used MIR lasers.ConclusionsWe pioneered the potential use of high-energy and nanosecond gas-filled ARHCF laser source to MIR-PAM, with a first attempt to report this kind of fiber laser source for PAM of lipid-rich myelin regions in a mouse brain. We also open up possibilities for expanding into a versatile multiwavelength laser source covering multiple biomarkers and being employed to image other materials such as plastics.
The emerging mid-infrared photoacoustic microscopy (MIR-PAM) is a potential imaging modality in revealing special biomolecules compositions in thick samples by utilizing the light-excited ultrasound signals. The development of a nanosecond and high-energy MIR fiber laser source is still at an early age, facing the challenges of either low peak power or large footprint. This work aims to develop a new Raman laser source for MIR-PAM based on the gas-filled anti-resonant hollow core fiber (ARHCF) technology. As a proof of concept, a MIR laser source at 3.4 μm is developed and combined with PAM for the first time targeting at the lipid-rich mouse brain sample due to main absorption band of myelin sheaths. This laser source is based on the cascading of two ARHCFs, where a high-energy (~26.5 μJ) Raman Stokes line at 1409 nm is generated through the 1st-stage nitrogen-filled ARHCF with a pump fiber laser at 1060 nm. The output Raman laser from the 1st stage ARHCF is used as a pump for the 2nd-stage hydrogen-filled ARHCF, to generate the Raman laser at 3.4 μm with ~2.7 μJ pulse energy. Our label-free ex-vivo imaging depicted the lipid-rich myelin region in the mouse brain, showing the feasibility of extending the novel gas-filled laser platform into PAM imaging modalities.
Due to their flexibility and robustness, polymer optical fibers represent a promising platform for the development of brain-compatible implantable devices with reduced risk of tissue inflammation. Furthermore, by combining different biocompatible materials it is possible to integrate multiple functionalities in a single hybrid optical fiber. This approach allows the fabrication of soft brain interfaces able to support multiple modalities of neural interrogation. Such interfaces capable of simultaneous light delivery and recording of neuronal activity with minimal tissue damage are currently lacking for infrared wavelengths in the strong water absorption region. This spectral region, in particular, is crucial for infrared neuromodulation, a promising technique for direct light-induced control of neural activity without genetic manipulation. Here we present novel infrared fiber-based neural interfaces developed by thermal drawing of soft, biocompatible optical polymers, which are able to simultaneously modulate and record neural activity, as validated experimentally in vivo.
Infrared neurostimulation has emerged in recent years as a promising technique for controlling neuronal activity without genetic manipulation. Having high absorption of the employed wavelengths as its fundamental mechanism, it requires implantable platforms to deliver light in brain regions deeper than the first cortical layers. Due to the spatial confinement of the stimulation, electrodes integrated in close proximity to the illumination spot are desirable to verify the effects of the stimulation by extracellular electrophysiology. Here we developed and validated in vivo a multifunctional neural interface based on a soft, biocompatible polymer optical fiber that allows simultaneous infrared neurostimulation and electrophysiology.
Implantable optical fibers have been widely used for optical neuromodulation in deep brain regions. Polymer fiber-based neural devices have natural advantages over silica fibers since their high flexibility would lead to a less inflammatory response in chronic in vivo experiments. Using three kinds of polymer materials: polycarbonate (PC), polysulfone (PSU), and fluorinated ethylene propylene (FEP), we present multifunctional soft polymer fiber (POF)-based brain implants with an Ultra-High Numerical Aperture (UHNA) and integrated Microfluidic Channels (MCs) for wide illumination and drug delivery, respectively. The flexibility of the proposed fiber devices has been found to be 100-fold reduced compared to their commercially available counterparts. Biofluids delivery can be controllably achieved over a wide range of injection rates spanning from 10 nL/min to 1000 nL/min by the structured MCs in the fiber cladding. The illumination area of the UHNA POFs in brain phantom has been increased significantly compared with the commercially available silica fibers. A fluorescent light recording experiment has been conducted to demonstrate the proposed UHNA POFs can be used as optical waveguides in fiber photometry. The limited illumination angle of the optical fiber imposed by current technology has been enlarged by the proposed UHNA POFs and we anticipate our work to pave the way toward more efficient multifunctional neural probes for neuroscience.
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