The critical shift to single-cell formats in functional analyses of living cells

Projektinformationen

Cellularity

ID Finanzhilfevereinbarung: 190144395

DOI

10.3030/190144395

Projekt abgeschlossen

EK-Unterschriftsdatum 14 Juli 2023

Startdatum 1 August 2023

Enddatum 31 Juli 2025

Finanziert unter

• The European Innovation Council (EIC)

Gesamtkosten

€ 4 926 042,50

EU-Beitrag

€ 2 500 000,00

Koordiniert durch

SAMPLIX ApS
Denmark

Periodic Reporting for period 2 - Cellularity (The critical shift to single-cell formats in functional analyses of living cells)

Berichtszeitraum: 2024-08-01 bis 2025-07-31

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

The development of new medicines is often hindered by a lack of data, despite data being essential to understanding the complex behavior of biological systems. To address this, scientists are increasingly applying large datasets to train and implement AI across many aspects of drug development.

However, current methods for generating data typically rely on cells grown in bulk populations, a process that is slow, costly, provides an insufficient amount of data, and obscures the biological heterogeneity that exists between individual cells.

Samplix has therefore developed Xdrop® Plus, a single-cell platform that enables functional analysis at true single-cell resolution. Instead of building a complicated and expensive system, Samplix has created a solution that prepares single cells for analysis on standard laboratory instruments, making the technology accessible to most laboratories.

The Xdrop Plus platform integrates instruments, microfluidic cartridges, reagents, other consumables, and software tools to support both experimental setup and data analysis.

The platform has already been proven, in peer-reviewed publications, to enhance the analysis of immune cells for immunotherapies such as tumour-infiltrating lymphocyte (TIL) treatments and CAR-T therapies.

It has also demonstrated significant value in the discovery and development of new antibodies, including therapeutics. With Xdrop Plus, millions of antibody-producing cells can be screened, allowing those with the desired functionality to be identified and further characterised.

Looking ahead, future applications of the technology include enzyme engineering to replace chemical processes with sustainable solutions, rapid vaccine development in response to pandemics, and high-throughput screening of molecular libraries for medical purposes.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

From a technical perspective, Xdrop® Plus encapsulates single cells, or pairs of cells, into tiny droplets that function as miniature vessels for single-cell functional analysis. Through co-encapsulation and the use of relevant functional dyes, specific cellular activities can be detected, such as:
• Release of granzyme B, a key molecule involved in killing cancer cells
• Release of cytokines, inflammatory signalling molecules
• Secretion of antibodies

The platform also enables co-encapsulation of immune cells together with cancer cells to directly assess the immune cells’ ability to exert their killing potential.

Cell behaviour within droplets can be visualised by imaging, analysed via flow cytometry, or sorted based on functionality using a fluorescence-activated cell sorter (FACS). Droplets containing cells of interest can then be opened, and the cellular content analysed by sequencing, thus combining advanced single-cell functional profiling with molecular profiling.

Key technical advancements during the project include:
• Development of a new droplet-encapsulation instrument, Xdrop Plus
• Introduction of two specialised microfluidic cartridges: DE20 for microbiology applications and DE50 for mammalian cell analysis
• A streamlined process capable of processing 8 samples in only 5 minutes
• User-friendly protocols to guide researchers through each step
• Digital tools to support optimal experimental design and provide troubleshooting assistance when needed

The Xdrop® Plus is designed for clinical research involving precious samples, featuring an integrated barcode reader for experimental documentation and an automated system that ensures nearly 100% of critical cells are successfully encapsulated in droplets.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

Key trends in cell research include a shift from bulk analysis to single-cell analysis, the replacement of robotics with microfluidics, the transition from low-dimensional to multidimensional data, and the move from spreadsheet-based analysis to AI-driven insights. Samplix is at the forefront of this market transformation.

The Cellularity Project takes a unique approach, aiming to democratise single-cell analysis - a technology that has, until now, largely been accessible only to large companies due to high costs.

The Samplix solution delivers at least ten times the capacity of existing systems while reducing costs to roughly one-tenth of current alternatives.

To capture the commercial opportunity, the technology must first be adopted by key opinion leaders (KOLs) who will publish results in peer-reviewed journals. To that end, Samplix has established partnerships with leading research organisations in the US and North America.

Furthermore, applications beyond the initial focus on immunotherapy and antibody discovery need to be documented and widely disseminated to expand market reach.

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