omniture

Single Cell Sequencing – the Current Players

2022-08-10 10:42

Normally, a mix of millions of cells is analyzed using traditional DNA or RNA sequencing methods via Sanger sequencing or high-throughput synthesis. But now, with single cell sequencing, we can investigate DNA and RNA from a single cell, unraveling cellular functions one base pair at a time. The single cell method is unlike traditional sequencings, which only provide an average expression of multiple cells, single cell sequencing brings a more precise assessment of each cell’s transcriptome.

Emerging as a powerful cancer research tool, single-cell analysis performs high-throughput sequencing on each cancer cell, enabling exploration of heterogeneity, microenvironment composition, and cell state transitions that affect therapeutic responses, particularly for immunotherapy. With ever-growing cancer diagnosis rate and research, the demand for single-cell analysis products is projected to grow. The global single-cell genomics manufacturer market reached $630M in 2019 and will grow at 23% annually to $1.5B in 2023.

Related article: How Single Cell Sequencing is Advancing Biomedical Research

From established names to promising disruptors, below is our curated list of players to keep tabs on:

10x Genomics

  • HQ: Pleasanton, California
  • Core Technology: Gel Bead-in-emulsion platform
  • Application: Single-cell gene expression, assay for transposase accessible chromatin (ATAC), immune profiling

Single cell genomics benefited from rapid growth mainly driven by 10x Genomics’ push on its Gel Bead-in-emulsion (GEM) platform to be the first commercially available high throughput single-cell analysis system for single-cell RNA sequencing. 10x first debuted its Chromium Single Cell Controller platform in March 2016 followed by commercial launch later that year. Since then, the company has generated revenue of $27M in 2016, $71M in 2017, $146M in 2018, and $246M in 2019, showing a staggering growth over 3 years.

While the first pandemic-related lockdowns brought non-COVID research to a standstill, 10x’s revenue since recovered to $114.5M as of Q1 2022, representing an 8% increase over the corresponding period of 2021.

Fluidigm

  • HQ: South San Francisco, California
  • Core Technology: Integrated microfluidic platform, cytometry
  • Application: mRNA sequencing, miRNA expression profiling, multi-omic single-cell assays

Fluidigm, now renamed to Standard BioTools, pioneered the single-cell field with its C1 platform, being the first tool to enable automated single-cell isolation (96 cells) and nucleic acid preparation based on microfluidics technology released in 2012. The end-to-end C1 system lets researchers prepare single-cell templates for mRNA sequencing, DNA sequencing, epigenetics, or miRNA expression and analyze them in under 4 hours.

In April 2022, the company secured a $250M capital infusion from leading life science investors Casdin Capital, LLC, and Viking Global Investors LP.

PacBio

  • HQ: Menlo Park, California
  • Core Technology: HIFI sequencing, Nanobind extraction, sequencing by binding
  • Application: Whole genome/targeted sequencing, metagenomics

PacBio specializes in long-read technology, a sequencing method optimal for larger DNA strands, at up to 50,000 bases. In the single cell space, the company’s HiFi technology delivers high accuracy and long reads needed to capture intact isoform information without assembly or complicated algorithms, at the single cell level. The Sequel II or IIe systems can generate 3 million full-length single-cell molecules from one of its SMRT Cell 8M kits to obtain 1,000 UMIs for 3,000 single cells. 

This May, PacBio announced a team up with iLAC and the Robotic Biology Institute to develop end-to-end automated workflows for its sequencing platforms, the Robotic Biology Institute is looking for ways to integrate its LabDroid humanoid robot into sequencing flows to achieve 24/7 uninterrupted high throughput capabilities. PacBio reported stable growth throughout the year; it saw revenue of $36.0 million in 2021, a 33% increase compared with $27.1 million in 2020.

Mission Bio

  • HQ: South San Francisco, California
  • Core Technology: Single-cell nucleotide variants (SNVs) and copy number variants (CNVs) analysis, simultaneous genotyping and phenotyping
  • Application: Oncology research, cell and gene therapy

Mission Bio offers a platform offering targeted DNA (co-occurrence of SNVs and CNVs), and recently multi-omics (DNA and protein) analysis. SNVs and CNVs are well tailored for translational oncology use, an area that is not 10x’s primary focus. Launching with targeted panels for acute myeloid leukemia (AML), the company expanded from a niche and demanded sector with more oncology research lineups to follow. Recently, it announced the Tapestri Platform updates for solid tumor research, utilizing the company’s variants core technologies for “unprecedented” clonal architecture, mutation co-occurrence, rare mutations, and therapy resistance tumor profile evaluations. 

Oxford Nanopore

  • HQ: Oxford, UK
  • Core Technology: Short to ultra long DNA/RNA sequencing, real-time direct sequencing
  • Application: Biomedical research, environmental genomics

Founded in 2005 as a spin-out from the University of Oxford, Oxford Nanopore based its sequence analysis technologies around the scaleable, real-time nanopore flow cells. The company’s sequencers range from the pocket-sized MinION to the larger PromethION adapted for clinical use. Long nanopore sequencing reads enable end-to-end sequencing of large genomic regions in single reads, effectively addressing limitations such as the inability to identify transcript abundance at the isoform level for single-cell transcriptome studies. The method is also useful for researching phenomena such as isoform switching observed during cell development.

In 2021, the company reached a value of about £4.95 billion at the session’s high after opening 28% above its initial public offering (IPO) price of 0.425. 2021 full-year total revenue was £133.7 million, compared to £113.9 million for 2020. Oxford Nanopore also beta-released Remora, a tool to enable high-accuracy, real-time methylation analysis with nanopore sequencing, to further differentiate itself from competitors.

Celsius Therapeutics

  • HQ: Cambridge, Massachusetts
  • Core Technology: Human tissue-focused single-cell RNA sequencing, automated machine learning pipeline
  • Application: Cancer and autoimmune disease precision medicines

This Cambridge-based biotech is running ongoing programs on in-depth single-cell RNA-sequencing of tissue samples from patients to understand molecular mechanisms relevant to human biology and to identify disease-causing genes. Leveraging its unique tissue-based discovery process, Celsius scaled its SCOPE (Single Cell Observations for Precision Effect) platform in 2021 to allow discovery of therapeutic targets of high interest in inflammatory bowel disease (IBD) and solid tumors, which in turn boosted its antibody-drug developments.

Celsius also announced that it raised another $83M in financing, consisting of a Series A extension and a Series B financing. The Series B financing was led by Casdin Capital, with participation from original investors Alexandria Venture Investments, GV, Heritage Provider Network and Third Rock Ventures and new investors Amgen Ventures, Amplitude Ventures, and Catalio Capital etc.

Illumina

  • HQ: San Diego, California 
  • Core Technology: Single-cell genomics analysis
  • Application: Downstream processing services

While players in the sample isolation and preparation market segment are facing intense competition, Illumina has enjoyed little to no threats in the downstream analysis market. Even though single-cell revenues may only be a fraction of Illumina’s revenue, it acknowledges the growth opportunities by positioning the NextSeq 1000 and 2000 systems for key single-cell processes. To capture this rapidly advancing market, the company markets diverse platforms targeting different needs, from high-throughput single-cell sequencing to multi-omics analysis suites. 

With the global single-cell analysis market valued at $2.2B in 2020, and an expected 15% CAGR from 2021 to 2028, we may expect the market to compete fiercely and major sector growth due to significant research and development activities. 

The single cell sequencing space is growing rapidly with huge potential in research, development, and clinical applications, please read the article titled How Single Cell Sequencing is Advancing Biomedical Research to learn more about the technology’s role in pushing the boundaries of medical sciences. 

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