Single-Cell Sequencing in 2024: High-Throughput, Lower Costs, and What’s Coming Next
My last blog post at The Single-Cell World Substack
This year brought a lot of exciting new developments in single-cell sequencing technology. I know there are still two months left in 2024, and we’re likely to see even more advancements. However, due to work commitments, I won’t be able to continue with this project much longer. I’ll explain why at the end of this post.
For now, let’s dive into single-cell sequencing technology: where we started in 2024, where we’re ending, and my predictions 🔮 for what’s coming in 2025.
1. 📈 High-Throughput Redefined
Just a few years ago, when explaining single-cell sequencing technology, I described 2 main options: low-throughput and high-throughput assays. Low-throughput typically refers to plate-based assays, allowing for the analysis of anywhere from a single cell to a few thousand cells in a cost-effective way. High-throughput meant analyzing tens of thousands to hundreds of thousands of cells per experiment, with these methods generally based on micro-, pico-, and nano-well technologies or droplet-based systems, which efficiently processed large cell numbers.
Starting in 2021, the concept of high-throughput began to shift. Parse Biosciences introduced scRNA-seq technology capable of analyzing 1 million cells in a single experiment. By 2024, Scale Biosciences had joined with similar technology, completely redefining high-throughput in the field. Now, I consider low-throughput to cover experiments with up to a few thousand cells, medium-throughput to range in the tens of thousands, and high-throughput to involve experiments with millions of cells.
🔮 Future Prediction
Looking ahead, throughput capabilities are set to keep expanding. The latest technologies and projects suggest a future where even larger datasets can be generated from a single experiment. For instance, Scale Bio’s 100 Million Cell Challenge with the Quantum Scale and the newly launched ParseGigaLab, which allows for the analysis of up to 10 million cells in one experiment, are pushing these limits. Takara, 10x Genomics, and BD Biosciences also have solutions now that allow increasing experiment throughput from medium to high.
These advances mean that today’s "high-throughput" standards will soon be overpassed, making ultra-high-throughput experiments more accessible and expanding the possibilities of single-cell research.
2. 💵 Making Single-Cell Affordable
A few years ago, more affordable single-cell RNA sequencing solutions started emerging from companies like Parse Biosciences, Fluent Biosciences, Scipio Biosciences, Singleron, Scale Biosciences, Honeycomb Biotechnologies, or SeekGene. This year, established players like BD Biosciences and 10x Genomics have also introduced more affordable options, accelerating the drop in prices.
A strong indicator that the science community needs lower prices comes also from Martelotto’s lab, which recently published a paper demonstrating how spatial imaging-based transcriptomics platforms can be used to study single-cell RNA at significantly lower prices. This approach, called STAMP, is well-suited for large projects like cell atlases and collaborative consortium efforts. Compared to the standard single-cell sequencing technology, STAMP enables at least a 10-fold reduction in cost per cell.
🔮 Future Prediction
In the coming years, I expect and hope scRNA-seq to become even more affordable. With competition and technological progress, the cost of analyzing millions of cells per experiment should continue dropping, making scRNA-seq feasible for more labs that currently lack access to this technology.
It would also be nice to see cost reductions for other single-cell sequencing technologies, like epigenetic, genetic, and multiomic approaches.
3. ➡️ The Next Wave of MultiOmic Approaches
At the start of 2024, “true single-cell multiomics” was predicted to be the next big trend. I’ll admit I was hoping for more technological breakthroughs in this area.
True multiomic assays have immense potential as the future of single-cell research—what could be better than capturing multiple layers of information from the same individual cell in one experiment (true multiomics) to understand how these layers interact and reveal more about cell behavior?
Currently, these assays haven’t yet been widely adopted on a large scale due to their high costs and complex workflows, which increase the risk of experimental failures and discourage some researchers from using them. Nonetheless, it’s promising to see companies like BD Biosciences focusing on developing new and more robust multiomic solutions.
🔮 Future Prediction
Looking ahead, I expect to see an increase in the variety of single-cell multiomics assays. If not within single-cell sequencing, I hope to see this growth in spatial omics approaches. Affordable multiomic assays would open up new possibilities for research, enabling more comprehensive studies.
4. ⬆️ The Rise of Long-Read Sequencing
While short-read sequencing remains the standard in single-cell sequencing experiments, 2024 has seen a shift toward long-read sequencing. Researchers have been repurposing 3’ end-biased cDNA to build libraries compatible with long-read platforms like PacBio and Nanopore, even though this workaround wasn’t ideal. To address this gap, this year ArgenTag introduced a ready-to-go (real) full-length sequencing kit, set to transform the field by providing complete transcript information for a more in-depth understanding of cellular diversity.
🔮 Future Prediction
As long-read sequencing gains momentum in single-cell RNA sequencing, I expect continued advancements and more kits to become available. The move toward full-length transcript sequencing is likely to become the new standard, offering comprehensive insights into isoforms and rare transcripts—essential elements for deeper understanding about cell function.
5. 📊 Data Analysis Made Easy for Biologists
One bottleneck in single-cell sequencing experiments is data analysis. Biologists, like me, usually lack the expertise to build data analysis pipelines. Besides, the ones that have a hybrid profile are overwhelmed with so much work.
To tackle this challenge, technology companies have made valuable progress by developing user-friendly software tailored for biologists, which has been a tremendous help. However, let’s be honest—this alone isn’t enough. These tools still fall short when it comes to enabling “deep analysis.”.
🔮 Future Prediction
As single-cell sequencing technology becomes more common in labs, software is evolving to make analysis more intuitive and accessible. New tools, like the one from Nygen, are enabling easy and reliable analysis without requiring extensive computational expertise.
6. 📸 Moving Beyond Snapshots to Cell Interactions and Functions
The future of single-cell technology is moving away from static snapshots and toward a dynamic understanding of how cells interact and function together. New technologies like Lightcast Bio, Partillion and Atrandi are enabling us to examine cellular interactions in real-time, revealing how cells influence each other in complex environments. This shift is essential for gaining insights into processes like immune responses, tissue regeneration, and tumor behavior.
🔮 Future Prediction
These tools will provide unprecedented insights into how cells interact with each other. If I were to write a new grant proposal, I would absolutely include them.
Conclusion
2024 has been an important year for single-cell sequencing technology. High-throughput capabilities have expanded, multiomic and long-read sequencing are gaining momentum, and costs are dropping. New user-friendly software has made data analysis easier for more scientists, though there’s still work to be done. What’s next?
🔮 Tools to see how single cells interact and function in real time, leading to new scientific discoveries.
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Why This Will Be My Last Blog Post at The Single-Cell World Substack?
For years, The Single-Cell World has been my passion project ❤️. I’ve loved sharing insights and helping researchers, and it’s been incredibly rewarding to connect with so many of you.
I explored ways to make the project sustainable, but it didn’t work out. So, I shifted to freelance science content creation, work that has continued to grow—a fun fact, mostly with companies outside of single-cell research. Since my day only has 24 hours, I’ve decided to focus on these types of projects.
Thank you to everyone who’s supported this journey—it’s been amazing to share it with you!
Cátia
Do you know Cellavision? I am wondering if this is a good company (investment opportunity). Thanks for sharing your knowledge :)