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Massively Multiparametric Flow Cytometer Analyzer

New Technology Development
Genome Centre(s):
Ontario Genomics
Project Leader(s):
Scott Tanner (University of Toronto)
Fiscal Year Project Launched: 
Project Description: 

Diagnosing a disease is most difficult at the early stages, where therapeutic intervention is most effective and least devastating. A patient’s sample contains many different cells, each of which can be distinguished and identified by the biomarkers (proteins, genes and small molecules) that comprise the cell’s biochemical signature.

Groundbreaking research in leukemia has advanced the belief that a particular disease may be sustained by only a small fraction of the diseased cells (“cancer stem cells” in the case of cancer), and is thus particularly difficult to detect and treat. The biomarker signature also reflects biochemical processes within the cells that determine cell activity and fate. Accordingly, the capability to measure the full signature of biomarkers at the same time for individual cells provides an opportunity for improved understanding of cell genesis and for the development of drugs to treat the disease.

Enormous progress is being made on the identification of diagnostic biomarker signatures and the understanding of biomarker interactions. Unfortunately, there are few analytical tools capable of recognizing these signatures, and these have serious limitations for detecting many biomarkers in a single analysis. Current single cell diagnostic technologies are based on the detection of fluorescent emission from tagged reagents that specifically recognize the biomarkers. While up to 10 detection channels can be monitored simultaneously, the approach is limited by poor resolution. This results in signal overlap and large errors when biomarkers are present over a wide range of concentrations.

There is a clear need for a new technology that will provide for the simultaneous quantitative and independent determination of many (up to 100) biomarkers in individual cells, especially where that analysis can be performed at high speed so that 1000 or more cells can be analyzed per second. The applicants are developing an innovative solution to this challenge that is receiving considerable enthusiasm from the scientific community. The approach takes advantage of the high resolution of mass spectrometry to distinguish biologically-rare metal atoms that replace the fluorescent dyes in current use. A new generation of diagnostic reagents that bind different metals to biomarkers is being developed. These “tagging metals” are detected with high sensitivity and resolution, and in a quantitative manner, by a prototype flow cytometer. This instrument introduces individual cells at a rapid rate, up to 1000 cells per second, to a multichannel mass spectrometer analyzer. In our current Genome Canada Applied Human Health (AHH) project, we were able to demonstrate the feasibility of this new technology.

The present proposal seeks to transform the complex research prototype instrument (and the reagents required for its operation) into an engineering prototype that will be made available to other Genome Canada researchers and that will subsequently be converted to a commercial instrument for widespread diagnostic and research use.

In addition to enabling genomics and proteomics researchers to achieve a vast improvement in the depth and range of cellular analysis, this project will provide a diagnostic tool that will define the new standard-of-care benchmark in hospitals, clinics and research departments world-wide.

The applicants bring long experience in the development of commercially successful analytical tools, and are ideally positioned to realize the project’s ambitious goals. The success of this project will lead to healthcare savings for Canadians and others worldwide, resulting from first-time-correct diagnosis and reduction in adverse drug reactions. It will advance international awareness of Canada as a leader in bioanalytical research. The commercial development of this mass spectrometer-based flow cytometer with its unprecedented multiplexing capabilities, along with its associated reagents technology development, will lead to many new highly-skilled jobs for Canadians and create millions of dollars of new revenue, much of it derived from export sales.


The technology developed in this project is expected to be transformative for the clinic. Personalized medicine relies on detailed genomic and proteomic information about each individual patient. Massively multiparametric biomarker analysis will provide improved personalized diagnosis leading to more targeted treatment, and hence a quicker and more effective therapeutic response. The result will be improved survival and recovery rates, and significantly reduced costs associated with adverse drug effects. Further, the technology will allow improved understanding of the molecular basis and control of disease, and will find important application in pharmaceutical drug development, leading to improved – and perhaps personalized – drugs.

DVS Sciences Inc. is commercializing the CyTOF™ instrument and MAXPAR™ reagent kits. The current business model anticipates selling 4 CyTOF™ instruments by the end of 2010, ramping up to sell 11 in 2011, and 30 in 2012. These instruments “read” the stable isotope tags provided in the MAXPAR™ reagent kits. By 2015, total sales of $112M are projected, approximately distributed as 58% instruments and 42% aftermarket (reagents and services). Efficiently addressing the world market requires the participation of an appropriate sales and marketing organization. At the end of the project (April 2010), DVS Sciences is negotiating with two potential distribution partners and two potential investors.

DVS Sciences intends to become a significant employer of highly skilled technical people. Depending on the financing achieved (i.e., the success in the negotiations mentioned above), the company expects to directly provide up to 48 new jobs in 2011, including 19 R&D positions. Continued success leads to projections of up to 226 employees in 2015, with 45 R&D, 66 production and 115 sales, marketing and administration positions, having a payroll of $20M. In addition, the company will outsource the manufacture of product components, much of it to Canadian suppliers resulting in approximately as many new indirect manufacturing jobs. The company expects to show a positive EBITDA in 2013, and strong sustained profitability in 2014, yielding a consequent substantial employment and corporate tax return.

The international flow cytometry business in 2010 is estimated to be $1.5B in 2010, according to reports by Strategic Directions International and Biocompare. That market segment is projected to grow to $3,7B in 2015. Today’s market share by function is approximately 60% Research & Development, 17% Clinical and 23% other. Consequently, DVS intends to focus initially on the research market segment, including clinical researchers who will develop the methods for specific clinical applications. Current regulations do not require rigorous clinical trials for analytical instrumentation, but equivalence to existing methods must be verified (typically through an FDA 510(k) application for a specific application). Early product placement will enable both clinical application development and method validation, and will lead to a focus on clinical diagnostics when feasible – anticipated for 2013