Spatial biology is among the smaller segments of the broader life sciences market. One estimate issued in August by Research And Markets, has the market growing from 2021-2028 at a 10% compound annual growth rate $484.22 million, which would put its value this year at just under $250 million.

The field made its way into the mainstream of genomic science when, under the term spatially resolved transcriptomics, it was unanimously recognized in January by editors of Nature as Method of the Year 2020: “This maintenance of spatial context is crucial for understanding key aspects of cell biology, developmental biology, neurobiology, tumor biology and more, as specialized cell types and their specific organization are crucially tied to biological activity and remain poorly explored on the scale of whole tissues and organisms.

Spatially resolved transcriptomics technology is being applied by large consortia, such as the Human Cell Atlas and Brain Initiative Cell Census Network (BICCN), with the ultimate goal of generating complete maps of large and complex tissues like the human brain, Nature also noted.

But to professionals in the specialty, the thrill of spatial biology is less about the numbers, or the recognition from a top-tier journal, than about the discoveries its technologies have made possible.

Two professionals discussed spatial biology at a September 2021 GEN Keynote Webinar, “Spatial Biology Redefines the Multiomics Approach”: Joe Beechem, PhD, Chief Scientific Officer and Senior Vice President of Research and Development at NanoString Technologies; and Arutha Kulasinghe, PhD, a Research Fellow and Leader of the spatial biology and liquid biopsy group at the University of Queensland’s Diamantina Institute in Australia.

Yoni Bock
Yoni Bock, PhD
Associate VP of Reagents R&D, Vizgen

“If you’re looking at an immune response, are those immune cells actually attacking a tumor cell or attacking a cell that is infected with coronavirus? These are things that you can figure out from spatial technologies that you could not figure out from previous technologies,” Yoni Bock, PhD, Associate VP of Reagents R&D with Vizgen, said June 16 on “GEN Live,” GEN’s monthly live-streaming video discussion series.

Vizgen is among companies appearing below in GEN’s first-ever top-10 A-List for spatial biology—the five largest public companies and five largest private companies—updated as of April 8. The public companies are ranked by their 2021 revenues as disclosed in regulatory filings, including sales of products or services, as well as revenue from collaborations and R&D activity. Private companies are ranked by the total capital they have raised, as disclosed by the companies themselves, either in press statements or in responses to GEN queries verifying figures compiled by other sources.

Also included in this list are eight “up-and-comers” that have either raised significant capital in recent months, shown positive data for their technologies, and/or launched significant new collaborations with partners.

Each company is listed with a short explanation of their recent activity.

 

TOP PUBLIC COMPANIES

5. Akoya Biosciences
Revenue: $54.917 million in 2021; $42.443 million in 2020

Akoya Biosciences went public in April 2021, raising approximately $138.2 million in net proceeds via IPO. Since then, Akoya—which calls itself “The Spatial Biology Company™—has joined microscope providers Nikon, CrestOptics, and Andor Technology to develop new spatial biology applications, and broaden access to Akoya’s PhenoCycler™ (Formerly CODEX®) single-cell multiplexed imaging solution through the the company’s Imaging Innovator’s (I2) Network of customer collaborators. Akoya also began partnering with AstraZeneca to advance new multiplex immunofluorescence (mIF) workflows and spatial biomarker signatures based on Akoya’s PhenoImager™ HT (formerly Phenoptics®) platform, aiming to elucidate the immune biology of cancer. PhenoImager HT was highlighted in the MITRE study, published in July 2021, in the Journal for ImmunoTherapy of Cancer, the first multi-institutional analytical demonstration of a spatial biology workflow. On March 14, 2022, Akoya reported a 29% year-over-year 2021 revenue jump, to $54.917 million, though its net loss more than doubled, to $42.935 million from $16.706 million in 2020.

breast cancer
A representative image of a breast cancer sample where the spatial proximity of two of the six biomarkers were analyzed in the tissue as part of the MITRE study, which demonstrated and validated an automated end-to-end workflow that characterized PD-1/PD-L1 immune checkpoint signaling in tumor tissue samples, using Akoya Biosciences’ PhenoImager HT multiplex immunofluorescence (mIF) platform. Measuring the proximity of PD-1+ and PD-L1+ cells in the tumor microenvironment, in addition to other spatial parameters, can enhance the predictive value of immunotherapy biomarkers. [Akoya Biosciences]
4. Fluidigm
Revenue: $130.581 million in 2021; $138.144 million in 2020

Fluidigm said April 1 that its shareholders had approved a $250 million strategic capital infusion from investors Casdin Capital and Viking Global Investors, which according to the company will help identify growth and cost opportunities for the company following the rebound of its base business during 2021. That rebound was driven by early customer orders for its new fourth-generation CyTOF® XT mass cytometry product. Two other Fluidigm technologies—Imaging Mass Cytometry™ (IMC™) and the Maxpar® Direct™ Immune Profiling Assay™—will be applied by the Abu Dhabi Stem Cells Center (ADSCC) for development of targeted stem cell therapies and research applications through a collaboration announced in February. In August 2021, Fluidigm inked a co-marketing agreement with privately-held Ultivue, through which the companies will offer imaging solutions for biomarker discovery and drug development.

A sagittal section of a normal adult mouse brain
A sagittal section of a normal adult mouse brain, imaged on NanoString Technologies’ Digital Spatial Profiler, is stained for neuronal protein alpha-synuclein (green) and DNA (blue) to illuminate intricate morphological structures for further expression profiling. Alpha-synuclein plays a crucial role in synaptic vesicle trafficking and neurotransmitter release. Accumulation and aggregation of alpha-synuclein is a hallmark of Parkinson’s disease and a therapeutic target of interest. [NanoString Technologies]
3. NanoString Technologies
Revenue: $145.085 million in 2021; $117.316 million in 2020

NanoString marked a milestone in the fourth quarter, as its nCounter instrument business grew its installed base to approximately 1,050 as of December 31, 2021, up 11% year-over-year. NanoString ended 2021 with a $115.254 million GAAP net loss (about $5 million more than 2020) on revenues that climbed 24% year-over-year, to $145.085 million in March. Another bright spot: NanoString recorded $18 million of GeoMx® Digital Spatial Profiler (DSP) instrument revenue, 48% year-over-year growth. The GeoMx installed base grew to approximately 255 GeoMx DSP Systems at December 31, 2021, representing 96% growth over 2020. The Whole Transcriptome Atlas (WTA) has driven a steady increase in demand for GeoMx consumables since its launch last year at the Third Annual Spatial Genomics Summit, reflected in 226% year-over-year growth to $17.1 million in 2021 consumables revenue.

2. 10x Genomics
Revenue: $490.490 million in 2021; $298.8 million in 2020

10x Genomics maintained its torrid growth pace in the fourth quarter, with revenues jumping 64% year-over-year to $490.490 million, and net losses narrowing to $58.223 million (from $542.731 million in 2020). In October 2021, 10x celebrated the grand opening of its Singapore manufacturing facility and commercial hub. In July, 10x launched its next-generation Chromium X Series for single cell analysis, enabling routine million cell experiments to run at 2 cents per cell. 10x has since announced plans to launch Chromium Fixed RNA Profiling and Chromium Nuclei Isolation products in mid-2022, as well as Chromium BEAM (Barcode Enabled Antigen Mapping) late this year. In June, 10x began shipping its new Visium Spatial Gene Expression for FFPE (formalin-fixed and paraffin-embedded) assay, giving researchers access to the whole transcriptome across their entire tissue.

1. Bruker
Revenue: $2.418 billion in 2021; $1.988 billion in 2020

Bruker has established a spatial biology beachhead over the past year, in part through a majority investment in Acuity Spatial Genomics, formed in March to advance spatial 3D genomics and multiomic analyses for discovery. Bruker invested $4.5 million, it disclosed in a regulatory filing. Acuity exclusively licenses from Harvard University its technology platform, designed to enable genome-wide visualization of spatially resolved 3D chromatin architecture in individual cells and cell populations in situ. In September 2020, Bruker acquired Canopy Biosciences, whose products and services include spatial biology. On August 5, the University of Pittsburgh added Canopy’s ChipCytometry™ to its Unified Flow Core in the Department of Immunology, to advance high-plex single-cell spatial biology research by quantifying cell phenotypes and their spatial relationships within the native tissue microenvironment.

 

TOP PRIVATE COMPANIES

5. Nucleai
Total Capital Raised: “Close to” $50 million

Nucleai said March 22 that it completed a $33 million Series B financing round jointly led by Section 32 and Sanofi Ventures, with participation by existing investors that included Debiopharm, Fosun RZ Capital, Vertex Ventures, and Grove Ventures. The company said it plans to use the new funding to further develop its platform and expand its commercial footprint across biopharmaceutical companies and contract research organizations (CROs), which are applying its technology throughout translational research, clinical trials, and novel applications for drug discovery. Founded four years ago, Nucleai has raised “close to” $50 million. Last September, it launched a strategic collaboration with Jefferson Health to discover spatial immunotherapy biomarkers, leveraging Nucleai’s ATOM platform and Jefferson’s repository of pathology and clinical data.

4. Vizgen
Total Capital raised: $51 million

Vizgen in January launched the broad commercial availability of its MERSCOPE™ Platform across the U.S., and released a second, open-access data set, the MERFISH Mouse Liver Map, along with an interactive web-based data visualization platform. MERSCOPE is designed to offer researchers insights into tissue-scale basic research and translational medicine in oncology, immunology, neuroscience, infectious disease, developmental biology, cell therapy, and gene therapy. In May 2021, Vizgen released the Vizgen MERFISH Mouse Brain Receptor Map, the first of a series of datasets made available through Vizgen’s Data Release Program. Also last year, Vizgen established a Scientific and Technical Advisory Board and named to it Susan Tousi, Illumina’s Chief Commercial Officer.

3. Lunaphore Technologies
Total Capital Raised: CHF 60 million ($65 million)

Bringing spatial technology into mainstream labs studying cancer and other diseases is the goal of Lunaphore Technologies. In February, Lunaphore announced the successful installation of its COMET™ PA instrument at Sweden’s SciLifeLab. As part of Lunaphore’s commercial strategy in 2022, both a new COMET™ PA and a LabSat® were installed at SciLifeLab—products integrated into the facility’s research infrastructure service offering, as well as ongoing research on colon and lung cancer. Also in February, Lunaphore partnered with Massachusetts General Hospital to develop an in vitro diagnostic (IVD) that evaluates sensitivity of solid tumors to poly-ADP ribose polymerase (PARP) inhibitors, with an initial focus on ovarian, breast and prostate cancers.

2. RareCyte
Total Capital Raised: $99.3 million

RareCyte’s sales business enjoyed more than 100% sales growth during 2021, a year during which the company completed a $24 million financing from new and existing investors. RareCyte says its Precision Biology™ solutions offer multiplexed analysis of cells and tissue for customers performing single cell applications in oncology and disease research to bring new therapeutics and diagnostic assays to market. In June, RareCyte announced a biomarker liquid biopsy assay for the neuroendocrine marker synaptophysin (SYP), designed to help customers evaluate SYP expression on circulating tumor cells (CTCs). The assay entails processing blood to slides with the AccuCyte® Sample Preparation System followed by staining with the RarePlex® 0920-VB Synaptophysin CTC Panel Kit, enabling blood-based investigation of a prominent mechanism by which tumors become resistant to second-line endocrine therapies.

1. Ultivue
Total Capital Raised: Over $100 million

With the addition of new executive team members in 2021 and over $100 million of funding raised to date, Ultivue has targeted spatial biology innovation to support much-needed biological insights from solid tumors. Its customers address the challenge of therapeutic response rates in patients undergoing immunotherapy using a bespoke kit-based approach that enables multiplex biomarker assays for tissue phenotyping and digital pathology. The company’s proprietary InSituPlex® technology is designed for quick and comprehensive exploration of biologically relevant markers combined with same slide-H&E analysis to provide more data from precious tissue samples. The entire assay can be run manually or on multiple different commercially available hardware platforms to support academic, biopharma, and CRO customers. In March, Ultivue and Aignostics launched a partnership to co-develop artificial intelligence (AI)-powered spatial multiplexed immunophenotype solutions for translational research groups and biopharma companies.

 

UP & COMERS

Advanced Cell Diagnostics (ACD)
When Bio-Techne acquired Advanced Cell Diagnostics (ACD) in 2016 for up to $325 million, it envisioned expanding into genomics technology and within clinical labs. One way ACD has helped Bio-Techne fulfill those goals has been through spatial biology, where the company in July 2021 expanded its RNAscope™ HiPlex platform, an advanced, in situ hybridization (ISH) tool created to understand vital gene expression patterns at single cell resolution. A month later, ACD announced that the U.S. Centers for Disease Control and Prevention (CDC) used RNAscope to visualize SARS-CoV-2 RNA directly in the autopsied tissues of suspected COVID-19 patients. RNAscope HiPlex v2 is designed to generate precise gene expression data, enabling comprehensive spatial studies from 12 targets in FFPE samples and up to 48 targets in Fresh and Fixed Frozen sample types.

Dovetail Genomics
Dovetail Genomics, an EdenRoc Sciences company that specializes in high-quality de novo genome assembly, announced a partnership of undisclosed value February 24 with Element Biosciences, developer of a new and disruptive DNA sequencing platform. The partnership is designed to demonstrate the value and performance of Dovetail’s proximity ligation-based next-generation sequencing (NGS) library prep solutions on Element’s AVITI System. Dovetail Genomics’ products and services are designed to capture 3D genome architecture alongside primary sequence information using NGS approaches. In January, Dovetail began partnering with Singular Genomics, developer of the G4 sequencing platform, to validate Dovetail’s proximity ligation kit portfolio in order to unlock access to 3-D genome architecture at the nucleosome level, which according to the company is critical for understanding the regulation of gene expression.

Ionpath
Ionpath survived a legal challenge from Fluidigm in March when, by joint motion of the companies, the US District Court for the Northern District of California dismissed a Fluidigm appeal of an earlier decision that Ionpath’s MIBIscope™ technology did not infringe on Fluidigm patents. Also in March, Australia’s Walter and Eliza Hall Institute of Medical Research said it would purchase a MIBIscope using a A$3.5 million ($2.6 million) Australian Cancer Research Foundation grant designed to fund creation of a multidisciplinary cancer research team focused on improving patient treatment options and investigating the cause of drug resistance. In January, Ionpath highlighted a paper published in Cell detailing how researchers deployed MIBI-TOP (multiplexed ion beam imaging by time of flight) to resolve precise cell locations, compositions, and functions using 37 proteins of interest.

Single Technologies
Single Technologies, whose 3-D sequencing technology is designed to enable both spatial and next-generation sequencing, brought its total capital raised to €5 million (about $6 million) in December 2020 by completing a heavily oversubscribed financing. Single was founded in 2014 following research in single-molecule imaging and biotechnology applications at Stockholm’s Royal Institute of Technology (KTH) combined with R&D in fiberoptic grating by founders of Proximion. Single raised a SEK15 million ($1.7 million) convertible loan in 2020. CEO Johan Strömqvist has said Single aims to open its first data sequencing production site in Stockholm by 2022.

Singular Genomics
Singular Genomics Systems launched its G4 benchtop sequencing platform in December 2021, promising to mount a serious challenge to longtime next-generation sequencing (NGS) leader Illumina by competing with two of Illumina’s top systems and appealing to customers seeking an alternative. Singular asserts that the G4 lives up to the company’s name in several ways, starting with its power output ranging from of 15 to 400 gigabases (Gb)—delivering at the high end up to 3x more data output per hour than other benchtop instruments—with run times for typical NGS applications starting at about five hours, up to between 16 and 19 hours for four complete human genomes. Singular said in March it was on track to begin shipping G4 instruments and F2 flow cell kits in the second quarter.

S2 Genomics
A manufacturer of automated tissue sample preparation systems, launched the Singulator™ 100 System, designed to automate the processing of solid tissue samples into suspensions of single cells or nuclei with high yields and from small samples for a wide range of single-cell biology and genomic analyses. The company followed up on its launch through distribution agreements with partners in Asia-Pacific, Canada, and Europe. In February, S2 entered into a collaborative marketing agreement of undisclosed value with S2 Genomics to co-promote Singulator 100 with Applied Cells’ MARS® Acoustics and Magnetic technologies as a complete workflow for tissue sample preparation.

Veranome Biosystems
Veranome Biosystems, an Applied Materials company, entered a collaboration and licensing agreement of undisclosed value with Cold Spring Harbor Laboratory (CSHL) in January that expanded the company’s spatial omics intellectual property portfolio into unbiased in-situ sequencing to address a broader set of applications with the Veranome Spatial Analyzer. The licensed portfolio includes BARseq in-situ sequencing assays and associated data analytics. Veranome and CSHL are developing a range of new applications using BARseq technology, particularly in neuroscience for highly multiplexed long-range neuro-mapping assays.

Visikol, a BICO Company
Visikol provides biopharmas with contract research services that include 3D cell culture, 3D tissue imaging, multiplex imaging, and digital pathology services. NJ-based Visikol was acquired in May 2021 for $7.5 million cash and stock by Swedish-based CELLINK (since rebranded BICO), the parent of 14 companies encompassing “bioconvergence” of biology, engineering, big data and AI. On March 14, Visikol said it is partnering with Molecular Instruments (MI) to offer HCR-based RNA FISH and IHC multiplex tissue imaging to its existing multiplex imaging service offering, enabling researchers to survey both multiplex protein expression and gene expression on the same slide.

 

*This table was updated – April 8, 2022.

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