Doctor of Philosophy, Chinese Academy Of Sciences (2017)
Development of an image biosensor based on an optogenetically engineered cell for visual prostheses.
Visual prostheses provide blind patients with artificial vision via electrical stimulation of surviving visual cells resulting in partial restoration of vision in many patients. However, high-resolution visual perception, long-term biocompatibility and safety remain the significant challenges of existing visual prostheses. Here, we present a novel method to develop a new visual prosthesis using living cells as integrated electronics and implantable microelectrodes. The living cells modified with channelrhodopsin-2 showed excellent light-sensitive properties and encoded image information with cellular deformations triggered by light stimulation. The photoresponsive properties of the cells were determined using a single pixel imaging system, which indicated that the cells can act as a good light-sensitive biosensor. Additionally, the imaging feasibility of the cells was further validated through successful and clear imaging of several object scenes using the same system. This work represents a step toward the design and use of living cells as an image biosensor for the development of a new generation of high-resolution visual prostheses.
View details for DOI 10.1039/c9nr01688k
View details for PubMedID 31184360
- Light-sheet microscopy in the near-infrared II window NATURE METHODS 2019; 16 (6): 545-+
Light-sheet microscopy in the near-infrared II window.
Non-invasive deep-tissue three-dimensional optical imaging of live mammals with high spatiotemporal resolution is challenging owing to light scattering. We developed near-infrared II (1,000-1,700nm) light-sheet microscopy with excitation and emission of up to approximately 1,320nm and 1,700nm, respectively, for optical sectioning at a penetration depth of approximately 750mum through live tissues without invasive surgery and at a depth of approximately 2mm in glycerol-cleared brain tissues. Near-infrared II light-sheet microscopy in normal and oblique configurations enabled in vivo imaging of live mice through intact tissue, revealing abnormal blood flow and T-cell motion in tumor microcirculation and mapping out programmed-death ligand 1 and programmed cell death protein 1 in tumors with cellular resolution. Three-dimensional imaging through the intact mouse head resolved vascular channels between the skull and brain cortex, and allowed monitoring of recruitment of macrophages and microglia to the traumatic brain injury site.
View details for PubMedID 31086342
- In situ printing of liquid superlenses for subdiffraction-limited color imaging of nanobiostructures in nature MICROSYSTEMS & NANOENGINEERING 2019; 5
In situ printing of liquid superlenses for subdiffraction-limited color imaging of nanobiostructures in nature.
Microsystems & nanoengineering
2019; 5: 1
The nanostructures and patterns that exist in nature have inspired researchers to develop revolutionary components for use in modern technologies and our daily lives. The nanoscale imaging of biological samples with sophisticated analytical tools, such as scanning electron microscopy (SEM) and transmission electron microscopy (TEM), has afforded a precise understanding of structures and has helped reveal the mechanisms contributing to the behaviors of the samples but has done so with the loss of photonic properties. Here, we present a new method for printing biocompatible "superlenses" directly on biological objects to observe subdiffraction-limited features under an optical microscope in color. We demonstrate the nanoscale imaging of butterfly wing scales with a super-resolution and larger field-of-view (FOV) than those of previous dielectric microsphere techniques. Our approach creates a fast and flexible path for the direct color observation of nanoscale biological features in the visible range and enables potential optical measurements at the subdiffraction-limited scale.
View details for PubMedID 31057928
View details for PubMedCentralID PMC6330505
- Photonic Nanojet Sub-Diffraction Nano-Fabrication With in situ Super-Resolution Imaging IEEE TRANSACTIONS ON NANOTECHNOLOGY 2019; 18: 226–33
- Developing a Bright NIR-II Fluorophore with Fast Renal Excretion and Its Application in Molecular Imaging of Immune Checkpoint PD-L1 ADVANCED FUNCTIONAL MATERIALS 2018; 28 (50)
Bright quantum dots emitting at 1,600 nm in the NIR-IIb window for deep tissue fluorescence imaging.
Proceedings of the National Academy of Sciences of the United States of America
2018; 115 (26): 6590–95
With suppressed photon scattering and diminished autofluorescence, in vivo fluorescence imaging in the 1,500- to 1,700-nm range of the near-IR (NIR) spectrum (NIR-IIb window) can afford high clarity and deep tissue penetration. However, there has been a lack of NIR-IIb fluorescent probes with sufficient brightness and aqueous stability. Here, we present a bright fluorescent probe emitting at 1,600 nm based on core/shell lead sulfide/cadmium sulfide (CdS) quantum dots (CSQDs) synthesized in organic phase. The CdS shell plays a critical role of protecting the lead sulfide (PbS) core from oxidation and retaining its bright fluorescence through the process of amphiphilic polymer coating and transferring to water needed for imparting aqueous stability and compatibility. The resulting CSQDs with a branched PEG outer layer exhibited a long blood circulation half-life of 7 hours and enabled through-skin, real-time imaging of blood flows in mouse vasculatures at an unprecedented 60 frames per second (fps) speed by detecting 1,600-nm fluorescence under 808-nm excitation. It also allowed through-skin in vivo confocal 3D imaging of tumor vasculatures in mice with an imaging depth of 1.2 mm. The PEG-CSQDs accumulated in tumor effectively through the enhanced permeation and retention effect, affording a high tumor-to-normal tissue ratio up to 32 owing to the bright 1,600-nm emission and nearly zero autofluorescence background resulting from a large 800-nm Stoke's shift. The aqueous-compatible CSQDs are excreted through the biliary pathway without causing obvious toxicity effects, suggesting a useful class of 1,600-nm emitting probes for biomedical research.
View details for PubMedID 29891702
Scanning superlens microscopy for non-invasive large field-of-view visible light nanoscale imaging
2016; 7: 13748
Nanoscale correlation of structural information acquisition with specific-molecule identification provides new insight for studying rare subcellular events. To achieve this correlation, scanning electron microscopy has been combined with super-resolution fluorescent microscopy, despite its destructivity when acquiring biological structure information. Here we propose time-efficient non-invasive microsphere-based scanning superlens microscopy that enables the large-area observation of live-cell morphology or sub-membrane structures with sub-diffraction-limited resolution and is demonstrated by observing biological and non-biological objects. This microscopy operates in both non-invasive and contact modes with ∼200 times the acquisition efficiency of atomic force microscopy, which is achieved by replacing the point of an atomic force microscope tip with an imaging area of microspheres and stitching the areas recorded during scanning, enabling sub-diffraction-limited resolution. Our method marks a possible path to non-invasive cell imaging and simultaneous tracking of specific molecules with nanoscale resolution, facilitating the study of subcellular events over a total cell period.
View details for DOI 10.1038/ncomms13748
View details for Web of Science ID 000389537800001
View details for PubMedID 27934860
View details for PubMedCentralID PMC5476830