Instrument-free 3D molecular imaging with the VOLumetric UMI-Network EXplorer

Introduction

Current molecular imaging and spatial transcriptomics methods are limited in throughput and affordability, and are constrained by inherent 2-dimensionality. We propose the Volumetric UMI Network Explorer (VOLUMINEX), a 3D implementation of sequencing-based microscopy.

Project Overview

This radical alternative to optical imaging builds spatial molecular maps by sequencing DNA barcode networks where:

• Each node is a clonally amplified DNA patch.
• Each edge indicates inter-node proximity.

The resulting network reveals gene identities along with their locations without a reference map.

Methodology

We propose an end-to-end pipeline starting with a tissue, followed by enzymatic processing steps, and ending with sequencing and a computational reconstruction to form a molecular image.

We envision this procedure as an off-the-shelf commercial kit, offering an inexpensive alternative to advanced imaging instrumentation, expanding access to more researchers and potentially even clinical diagnostic settings.

Team Composition

We are led by a Stockholm-based tech-dev team with seminal contributions to the field of sequencing-based microscopy, and a Stockholm-based company, Single Technologies AB, with a proprietary 3D sequencing device uniquely suited for validating our technology.

We have partnered with an Utrecht-based team of life scientists to develop and deploy our technology on organoids, a rich controllable model tissue-like system perfect for exploring 3D biological imaging.

Theoretical Foundations

Finally, at the heart of the project are undiscovered laws and physical principles which we aim to uncover and exploit with our Paris-based team of theoreticians. They will develop optimization, graph theory, and machine learning algorithms to tackle the challenging computational problem of spatial reconstruction presented by sequencing-based microscopy.

Conclusion

Through VOLUMINEX, we aim to kick off a new era of molecular imaging where comprehensive spatial and transcriptomic data is accessible, affordable, and 3-dimensional.