LAMBDA'S DAILY OPERATIONS
Found out more detail about Lambda Neuroscience Foundation's laboratory operation, learn a bit more about histology, and explore what sets Lambda's method apart.
THE OVERALL PROCESS
Lambda operates as a free, specialized, and outsource histology service for neuroscience laboratories. Researchers conduct their experiments and generate brain tissue samples within their laboratories, then send those samples to Lambda, similar to the process of medical doctors sending in patient biopsies for lab analysis. Lambda performs the downstream sample processing needed to transform tissue into rigorous, highly granular digital image datasets that are indexed and available to reserachers through our database website. The goal is to provide researchers with a more information-rich view of the brain that is standardized across brain disease models to facilitate new molecular comparisons/insights, while reducing the technical and financial burden placed on individual laboratories.
WHAT HAPPENS IN THE LAB
Step 1: Prepare the slides by frist using the Leica vibratome to make precise and reproducable brain sections, starting from the front slowing moving to the back. Then gently align the sections on the slide and allow them to air dry so they adhere to the surface of the slide glass.
Step 2: Incubate the brain sections on the slides first with a mixture of primary (1°) antibody each recognizing a specific structure in the tissue, followed by a mixture of secondary (2°) antibody which labels the structure/primary complex in a specific color (aka, a specific channel during imaging).
Step 3: Image the individual sections on the slides at high resolution on the Leica fluorescent microscope in multiple channels (7 total, 6 used for cellular identification).
DIGTAL IMAGE ANALYSIS & POST PROCESSING
Channel signal provides information about tissue: Within a single channel, the cells making up the tissue can either be postive or negative. With two channels (red and green) it is possible to distinguish four cellular populations: R-/G- (double negative), R+/G- (red), R-/G+ (green), R+/G+ (double postive). Individual imaged tissue sections can be projected together using software to make a digital 3D rendering representing a volume of the tissue sample.
WHY LAMBDA'S METHOD IS SUPERIOR
THE LAMBDA DIFFERENCE
Histology (microscopic analysis of biological tissue) is one of the principal ways scientists study how disease alters the brain as it allows visualization of molecular changes at the single cell level. Yet in many conventional workflows, analysis is limited to selected regions of the brain and relatively few imaging channels, which constrains how much information can be extracted from a given specimen. Lambda’s model is intentionally designed to expand both the scale and the detail of tissue visualization.
Typically only 2 channels are used, allowing the researcher to identify 4 separate cellular populations. But with Lambda's method, up to 6 channels can be used allowing for 64 popultions to be identified simultaneously (a 16x increase). By combining broader brain coverage with higher-dimensional imaging, the foundation aims to help researchers "see" brain diseases in an unprecedented and complete way. This comprehensive appoarch to whole brain visualiztion aims to ultimately lead to new insights into disease progression, and most importnatly to potential new therapies.
