Drug Discovery Applications
Understanding the subcellular landscape is a critical challenge in drug discovery,
compounded by the limitations of existing tools. Electron Microscopy delivers
remarkable ultrastructural detail at the nanoscale, and Fluorescence Microscopy provides distinct molecular specificity. But neither technique can deliver both at the same time. And so, identifying and validating disease biomarkers, therapeutic targets and biologics – especially within organelles like lysosomes, endosomes, mitochondria and the Golgi apparatus – still depends on correlations and is subject to localization biases.
pan-ExSt technology allows researchers, for the first time, to capture both
ultrastructural detail and molecular specificity concurrently and in 3-D. Using a
standard light microscope, scientists can now catalogue the molecular organization of
disease biomarkers and biologics at an unprecedented sub-organelle scale, bridging the
gap between discovery and function. Some key applications include:
Targeted Drug Development
With pan-ExSt, researchers can precisely examine how drug candidates interact with biomarkers at the subcellular level, enhancing the efficacy and safety of potential therapies.
Accurate biomarker localization is crucial in validating their significance as disease indicators. pan-ExSt provides a robust platform to optically assess the relevance and reliability of potential biomarkers.
Therapeutic Efficacy Assessment
Mechanism of Action Studies
By visualizing drug biologics and ADCs in cellular contexts, pan-ExSt facilitates the evaluation of treatment efficacy, streamlining the drug development process.
Unveiling the 3-D molecular organization of biomarkers sheds light on their interactions within cells, deciphering the mechanisms of disease and pathways for intervention.
Below are illustrative examples of organelles that have been imaged with pan-ExSt:
3-D reconstructed mitochondrion
panluminate has experience processing cells grown on coverslips or suspended in solution. Our expertise extends from common research cell lines like HeLa, CHO, HEK293, A549, RPE, and U-2 OS to embryonic stem cells and hematopoietic cells.
Pre-Clinical Drug Development Applications
Understanding the safety, efficacy, and pharmacology of lead compounds are critical challenges at the pre-clinical phase of drug development. But these challenges, too, are compounded by both the complexity of tissue analytics and the limitations of existing tools. panluminate has pioneered a transformative new approach to solve both.
Progressive Subcellular Interrogation (PScI) is a multi-resolution, multi-modal, and multiplexed imaging technology. For the first time, investigators can analyze the same sample at the whole tissue, single cell, and nanoscale levels. This is spatial proteomics – offering tissue level single cell mapping – but in 3-D and without tissue degradation. Then PScI goes deeper to reveal the nanoscale landscape of ROIs from the same tissue sample with comprehensive ultrastructural and molecular precision.
PScI has been used to correlate specific biomarkers and biologics distributions (like ADCs) in a wide range of biological contexts, including the tumor microenvironment and fibrotic human lung tissue. It delivers comprehensive data, cataloguing rather than extrapolating biomarker validations for pre-clinical evaluations.
The following illustrations showcase subcellular ultrastructural details in tissue samples, revealed with PScI.
Organelles in the dividing cells of breast cancer tissue
Renal mitochondria in response to a perturbation
An amyloid plaque core
Astrocytes engulfing blood vessels in brain tissue
The kidney glomerulus
panluminate has experience handling brain, lung, breast, liver, and kidney tissues from animal models of neurodegeneration, cancer, and fibrosis. We also developed a new way to preserve, process, and localize biologics in patient-derived xenograft (PDX) tissue. With a new optimized pipeline, we help companies in the drug pre-clinical development stage visualize their targets of interest within complex tissue structures.
Sample Processing for Brain Connectomics
panluminate’s technology is ideally suited to realizing one of the most ambitious projects in modern biology: mapping the entire mammalian brain, sometimes called the “connectome”. Before pan-ExSt, Electron Microscopy (EM) seemed the only viable tool for this task, despite two major limitations. First, 3-D mapping with EM is arduous, costly and destructive; it requires sectioning thousands of tissue layers for 2-D imaging and reassembling them as a composite. Second, without specific molecular labeling, tracing neurons and differentiating cells is even more challenging.
panluminate’s unique combination of ultrastructural detail at nanoscale and ability to precisely localize proteins in 3-D is a game changer in connectomics. Brain tissue processed with pan-ExSt reveals dendrites, axons, synaptic densities, and membrane boundaries with unmatched clarity. It is the only technology that can generate molecularly annotated neural circuits using light microscopy, realizing the dream of connectomics and improving quality, speed and costs by orders of magnitude.
Below are examples of brain tissue ultrastructural features revealed with pan-ExSt:
panluminate provides sample prep services for labs and companies that either conduct large-scale connectomics projects or develop neuronal tracing algorithms for connectomics analysis.