Fluorescence is a powerful mean to probe information processing in the mammalian brain. However, neuronal tissues are highly heterogeneous and thus opaque to light. A wide set of non-invasive or invasive techniques for scattered light rejection, optical sectioning or localized excitation, have been developed, but non-invasive optical recording of activity through highly scattering layer beyond the ballistic regime is to date impossible. Here, we show that functional signals from fluorescent time-varying sources located below an highly scattering tissue can be retrieved efficiently, by exploiting matrix factorization algorithms to demix this information from low contrast fluorescence speckle patterns.
Phantom eye devices are designed to mimic the optical properties of the human eye; however, the retinal structures are typically emulated with synthetic tissues. Thus, it is currently impossible to exploit phantom eye devices for fluorescence microscopy experiments on cultures, or ex-vivo tissues, although these ophthalmic measurements would be of importance for many applications such as the testing of retinal biomarkers. Here we report and describe the development of a phantom eye designed to host biological samples, such as retinal cultures differentiated from human induced pluripotent stem …
Light and Sound Driven Wavefront Shaping and Imaging through Scattering Tissue
Laboratoire Kastler Brossel, ENS-Universite PSL, CNRS, Sorbonne Université, Collège de France（卡斯勒布罗塞尔实验室，巴黎高等师范学院-PSL大学，法国国家科学研究中心，索邦大学，法兰西学院）；European Molecular Biology Laboratory（欧洲分子生物学实验室）；Nhu Department of Electrical Engineering and Computer Science, University of California, Irvine（加州大学尔湾分校电气与计算机工程阮部）
Fluorescence microscopy is a powerful tool for imaging biological samples with molecular specificity. In contrast, phase microscopy provides label-free measurement of the sample's refractive index (RI), which is an intrinsic optical property that quantitatively relates to cell morphology, mass, and stiffness. Conventional imaging techniques measure either the labeled fluorescence (functional) information or the label-free RI (structural) information, though it may be valuable to have both. For example, biological tissues have heterogeneous RI distributions, causing sample-induced scattering th…
Deep fluorescence imaging in mammalian brain tissues remains challenging due to scattering and optical aberration-induced loss in signal and resolution. Correction of aberrations using adaptive optics (AO) requires their reliable measurement in the tissues. Here, we show that an extended-source Shack-Hartmann wavefront sensor (ESSH) allows quantitative aberration measurements through fixed brain slices with a thickness up to four times their scattering length. We demonstrate in particular that this wavefront measurement method based on image correlation is more robust to scattering compared to…
Aberration sensing in fluorescence microscopy using quantum correlations
Weizmann Institute of Science（魏茨曼科学研究所）；Sorbonne Université, CNRS, Institut des NanoSciences de Paris, INSP（索邦大学，法国国家科学研究中心，巴黎纳米科学研究所）；Georg-August-Universität（哥廷根大学）
$μ$NeuFMT: Optical-Property-Adaptive Fluorescence Molecular Tomography via Implicit Neural Representation
School of Information Science and Technology, ShanghaiTech University（信息科学与技术学院，上海科技大学）；School of Mathematics, University of Birmingham（数学学院，伯明翰大学）；School of Physical Science and Technology, ShanghaiTech University（物理科学与技术学院，上海科技大学）；Institute of Medical Robotics, School of Biomedical Engineering, Shanghai Jiao Tong University（医学机器人研究所，生物医学工程学院，上海交通大学）；State Key Laboratory of Advanced Medical Materials and Devices, ShanghaiTech University（先进医学材料与器件国家重点实验室，上海科技大学）
Two-photon absorption (TPA) fluorescence of biomarkers has been decisive in advancing the fields of biosensing and deep-tissue in vivo imaging of live specimens. However, due to the extremely small TPA cross section and the quadratic dependence on the input photon flux, extremely high peak-intensity pulsed lasers are imperative, which can result in significant photo- and thermal-damage. Previous works on entangled TPA (ETPA) with spontaneous parametric down-conversion (SPDC) light sources found a linear dependence on the input photon-pair flux, but are limited by low optical powers, along with…
We demonstrate the preservation of time-energy entanglement of near-IR photons through thick biological media ($\leq$1.55 mm) and tissue ($\leq$ 235 $μ$m) at room temperature. Using a Franson-type interferometer, we demonstrate interferometric contrast of over 0.9 in skim milk, 2% milk, and chicken tissue. This work supports the many proposed opportunities for nonclassical light in biological imaging and analyses from sub-shot noise measurements to entanglement-enhanced fluorescence imaging, clearly indicating that the entanglement characteristics of photons can be maintained even after propag…
Non-invasive optical focusing inside scattering media is still a big challenge because inhomogeneous media scatter both incoming photons for focusing and outgoing photons for observation. Various approaches, utilizing non-linear fluorescence or ultrasound, have been reported to address this difficulty. However, implementation of these methods is complicated and highly expensive, as ultrafast laser systems or photo-acoustic equipment must be employed. Here, we demonstrate a wavefront shaping technique to achieve non-invasive focusing (NiF) inside scattering media using only a linear fluorescent…
On-chip scalable integration represents a major challenge for practical quantum devices. One particular challenge is to implement on-chip optical readout of spins in diamond. This readout requires simultaneous application of optical and microwave fields along with an efficient collection of fluorescence. The readout is typically accomplished via bulk optics and macroscopic microwave transmission structures. We experimentally demonstrate an on-chip integrated structure for nitrogen vacancy (NV) spin-based applications, implemented in a single material layer with one patterning step. A nanodiamo…
Fluorescence microscopy and derived techniques are continuously looking for photodetectors able to guarantee increased sensitivity, high spatial and temporal resolution and ease of integration into modern microscopy architectures. Recent advances in single photon avalanche diodes (SPADs) fabricated with industry-standard microelectronic processes allow the development of new detection systems tailored to address the requirements of advanced imaging techniques (such as image-scanning microscopy). To this aim, we present the complete design and characterization of two bidimensional SPAD arrays c…
In analogy to the development of fluorescent proteins, innovative tools for screening optoacoustic cell labels could lead to tailored protein labels for OA, imparting novel ways to visualize biological structure and function. Optoacoustic imaging emerges towards a highly promising modality for life sciences and medical practise with advantageous capabilities such as great accessible depth, and 3D studying of living tissue. The development of novel labels with molecular specificity could significantly enhance the optoacoustic contrast, specificity, and sensitivity and allow optoacoustic to inte…
Center of Advanced European Studies and Research (caesar)（欧洲高级研究中心 (caesar)）
Aberrations limit scanning fluorescence microscopy when imaging in scattering materials such as biological tissue. Model-based approaches for adaptive optics take advantage of a computational model of the optical setup. Such models can be combined with the optimization techniques of machine learning frameworks to find aberration corrections, as was demonstrated for focusing a laser beam through aberrations onto a camera [arXiv:2007.13400]. Here, we extend this approach to two-photon scanning microscopy. The developed sensorless technique finds corrections for aberrations in scattering samples …
EvidenceMoE: A Physics-Guided Mixture-of-Experts with Evidential Critics for Advancing Fluorescence Light Detection and Ranging in Scattering Media
Center for Modeling, Simulation, & Imaging in Medicine（建模、仿真与成像医学中心）；Rensselaer Polytechnic Institute（伦斯勒理工学院）；University at Albany（阿尔巴尼大学）；IBM T.J. Watson Research Center（IBM 沃森研究中心）
