Subvoxel light-sheet microscopy for high-resolution high-throughput volumetric imaging of large biomedical specimens

A key challenge when imaging whole biomedical specimens is how to quickly obtain massive cellular information over a large field of view(FOV).We report a subvoxel light-sheet microscopy(SLSM)method enabling high-throughput volumetric imaging of mesoscale specimens at cellular resolution.A nonaxial,continuous scanning strategy is developed to rapidly acquire a stack of large-FOV images with three-dimensional(3-D)nanoscale shifts encoded.Then,by adopting a subvoxel-resolving procedure,the SLSM method models these low-resolution,cross-correlated images in the spatial domain and can iteratively recover a 3-D image with improved resolution throughout the sample.This technique can surpass the optical limit of a conventional light-sheet microscope by more than three times,with high acquisition speeds of gigavoxels per minute.By fast reconstruction of 3-D cultured cells,intact organs,and live embryos,SLSM method presents a convenient way to circumvent the trade-off between mapping large-scale tissue(>100 mm3)and observing single cell(∼1-μm resolution).It also eliminates the need of complicated mechanical stitching or modulated illumination,using a simple light-sheet setup and fast graphics processing unit-based computation to achieve high-throughput,high-resolution 3-D microscopy,which could be tailored for a wide range of biomedical applications in pathology,histology,neuroscience,etc.

System control-mediated drug delivery towards complex systems via nanodiamond carriers

Cells represent the basic units of life and contain an intertwined network of signaling and regulatory circuitries that drive the processes of life.These processes include the mediation of mechano-sensation,onset of and protection against disease,inflammation,and others.In the network of bio-complex systems,each pathway interacts nonlinearly with others through different molecular intermediates.As a result,specific functionalities can not be simply linked to the cellular molecules in isolation.A complex system generally possesses very rich information content that can be characterized by the following features:(i)they contain a large number of building blocks;(ii)their interactions among building blocks and with their environment;(iii)they display organization without an external organizing principle being applied;and(iv)they exhibit adaptability and robustness.These properties account for the innate intelligence of biology and its ability to regulate its homeostatic behavior.However,this same complexity underlies,in cancer for example,challenges towards disease management,as the addressing of singular pathways with therapeutic compounds is not sufficient.Therefore,combinatorial therapy often serves as a key strategy towards tumor suppression.Because iterative searching for optimized therapeutic combinations is indeed a daunting,if not preclusive task,we introduce the feedback system control(FSC)scheme,which may serve as a clinically relevant approach,provided a translational approach towards drug delivery is employed.Due to their innate biocompatibility,which has been comprehensively observed,as well as their ability to delivery virtually any type of therapeutic in a sustained fashion due to their unique surface properties,nanodiamonds may serve as a foundation for nanoenabled combinatorial therapy.