Flow cytometry tools are now smaller, more powerful, and more affordable

The origins of flow cytometry date back to the late 1940s with electrical engineer Wallace H. Coulter’s development of a technology that could count, classify, detect, and analyze the chemical and physical characteristics of cells and particles in fluid as they moved. It was a breakthrough that prompted Wolfgang Göhde, a researcher at the University of Münster (Germany), to establish flow cytometry by creating the first fluorescence-based flow cytometry device in the late 1960s. It was a game-changer.

Initially, flow cytometry – originally termed pulse cytophotometry – could count and analyze a small amount of cells with just a few parameters. Today, this technology can analyze thousands of cells (measured with more than 20 parameters) rapidly in real time, producing highly accurate data. It is ideal for applications in biomedical research – specifically, where accuracy is crucial.

Global market dynamics
The global flow cytometry market size was valued at USD 5 billion in 2022, and is expected to grow at a compound annual growth rate (CAGR) of 7.07 percent from 2022 to 2030. The growing prevalence of cancer, immunodeficiency disorders, and infectious diseases is driving industry growth. Moreover, rising R&D investments in biotechnology, life science, and biopharmaceutical research activities have also led to high demand for flow cytometry instruments. In addition, technological advancements in the technique are introducing new and improved analytical tools, which include the development of microfluidic flow cytometry for point-of-care (POC) testing.

Product insights. The instrument segment dominated the global industry in 2022 and accounted for the largest share of more than 35.2 percent owing to the higher penetration coupled with technological advancements. In January 2022, Sony Biotechnology, Inc. introduced its CGX10, a new closed-cell isolation system for use in GMP-compliant cell-sorting applications. The initiative was expected to open new growth opportunities for the company. Such advancements in technology result in cost-effectiveness, enhanced accuracy, portability, and are likely to create future growth opportunities.

Small-sized high-throughput cytometers are likely to gain acceptance in the coming years. This is due to allied advantages, such as user-friendliness and cost-effectiveness. The software segment is expected to witness a significant growth rate over the next 8 years. The software in flow cytometry is used to control and acquire data generated by cytometers, analyze the information, and provide statistical analysis of the outcomes. For research purposes, the software is used for cell acquisition and data analysis, while in clinical diagnosis, it is used for disease diagnosis by analyzing patients’ samples.

Such wide applications are projected to boost the industry in near future. Moreover, new product developments by key companies are among other significant factors driving the segment growth. In September 2022, BD announced the launch of a BD software solution specifically designed for flow cytometry workflow. This software enables higher-quality experiments with faster time to insight for scientists working in various disciplines, such as oncology, virology, immunology, and infectious disease monitoring.

Technology insights. The cell-based flow cytometry technology segment dominated the industry in 2022 and accounted for the maximum share of more than 77.25 percent of the overall revenue. Increasing awareness about the benefits associated with cell-based assays and rising demand for early diagnosis are factors contributing to its dominance. Furthermore, technological advancements in cell-based assays, such as innovation in software, instruments, algorithms, affinity reagents, and labels, are expected to drive the adoption in the coming years. The bead-based assay segment is estimated to grow at a significant CAGR in coming years.

Bead-based flow cytometry is used to measure various intracellular soluble proteins, including growth factors, cytokines, chemokines, and phosphorylated cell signaling proteins. High-throughput flow cytometry technique is considered an optimal tool for conducting multiplex bead-based assays. Multiplex bead-based technique has high growth potential in the field of research, diagnosis, and treatment of infectious diseases. The need for these assays is expected to show lucrative growth in the coming years owing to advancements in monoclonal antibody production and molecular engineering and the accompanying advantages, such as cost-efficiency, short turnaround time, and micro-sampling capabilities.

Application insights. The clinical segment accounted for the largest share of more than 45.9 percent in 2022. This high share can be attributed to increasing research and development activities pertaining to cancer and infectious diseases, including Covid-19. Furthermore, rising R&D investments in the biotechnology and pharmaceutical industry are likely to create a conducive environment for market growth. In addition, unceasing growth strategies by key players in the industry and the launch of novel flow cytometry solutions for clinical applications are also anticipated to significantly support the segment growth. In March 2022, Beckman Coulter launched CellMek SPS, which is a powerful solution for data management and manual sample preparation bottlenecks in clinical flow cytometry. The industrial segment is expected to register the fastest CAGR over the next 8 years.

This is due to the increasing applications of flow cytometry in cell culture. The technique finds applications in the pharmaceutical industry, such as drug development process including, target identification, drug characteristics, and compound screening, non-clinical safety and toxicity evaluation, and clinical research. Flow cytometry offers a high throughput and rapidity for large-scale drug development and testing detects multiple parameters on the cell surface, coupled with data analysis generates complex and sufficient data by excluding false positives in single-parameter tests. The associated advantages of using flow cytometry in large-scale bioprocessing operations for drug development are expected to fuel market growth in coming years.

End-use insights. The academic institutes segment accounted for the highest revenue share of more than the market in 2022. The technique is used in cell biology and molecular diagnostic studies to measure cell parameters, such as the physical properties of cells and recognition of biomarkers through specific antibodies, cell type, cell lineage, and maturation stage. This technology has applications in several educational fields, including molecular biology, immunology, pathology, plant biology, and marine biology. With rising R&D activities, the segment is expected to exhibit significant growth.

The clinical testing labs segment is anticipated to register the fastest CAGR from 2022 to 2030. This is due to the growing need for cost-effective diagnosis of target diseases, such as cancer. It is a widely used tool in the diagnosis and treatment of cancers and immunodeficiency diseases. The rising prevalence of cancer and chronic diseases has resulted in a high demand for diagnostic tests, which is expected to drive the demand for the technique in clinical testing laboratories over the few years.

Regional insights. North America dominated the overall industry and accounted for the largest share of more than 40.85 percent of the revenue in 2022. This dominance is due to the high implementation of scientifically advanced flow cytometry solutions, high healthcare expenditure, and well-established healthcare infrastructure in the US. In addition, widespread research activities by research universities and the presence of established pharmaceutical companies have generated a huge demand for flow cytometry workflow for research needs. In addition, the high prevalence of infectious and chronic diseases, including the outbreak of Covid-19, has led to an increase in the demand for the technique for research and diagnosis purposes.

Asia-Pacific is anticipated to witness significant growth as a result of the growing pharmaceutical and biotechnology industries in emerging economies, such as China and India. The industry is driven by the growing incidence of chronic diseases and the increasing use of cytometry devices in various applications in the region. Moreover, ongoing innovations in the fields of cancer and infectious illnesses, such as Covid-19, are expected to drive the regional market. In addition, extensive research activities by regional players for the improvement or development of innovative flow cytometry solutions are expected to support market growth in the region.

Some of the prominent players operating in this market are Becton, Dickinson and Company, Danaher Corporation, Thermo Fisher Scientific, Inc., Luminex Corporation, Agilent Technologies, Inc., Sony Group Corporation, Bio-Rad Laboratories, Inc., Miltenyi Biotec GmbH, Apogee Flow Systems Ltd., BioMérieux S.A., Cytek Biosciences, Inc., NanoCellect Biomedical, Inc., among others.

A complex tool
Flow cytometers are complex optical tools that have benefited from miniaturized solid-state lasers and affordable CCD, CMOS, and p-i-n detectors. The solid-state lasers used today require much less power and space, and less complex optics, and they are altogether more compact and robust.

One of the main drivers of the shift from gas lasers to solid-state lasers in flow cytometry was the technology used in CD players. As CD player sales soared into the millions and the CD-ROM made its debut, laser diodes became affordable for medical tools as well.

Infrared diode lasers (808 nm) were also developed in large quantities and used in diode-pumped solid-state (DPSS) lasers – emitting at 1064 nm and frequency doubled to 532 nm – the most common laser type used in flow cytometry today.

Further developments enabling affordable flow cytometry include new laser diode packaging technologies that improve manufacturing and package thermal resistance, as well as sub-millimeter proximity of various wavelength laser dies. The RGB lasers used as picoprojectors for head-up display and near-to-eye virtual and augmented reality require a tiny form factor. These same technologies could be applied to medical devices, and could enable pocket-sized flow cytometers that could be delivered to a sick patient in a remote area, or used for continuous monitoring of patients in ambulances. These potentially life-saving devices would require a multi-wavelength laser module that is integrated into a compact package.

Most flow cytometers use photomultiplier tubes for detecting the scattered light signal, because a much higher signal-to-noise ratio is required to detect very faint light scattered by single cells. In this part of the flow cytometer, substitutes for the bulky photomultiplier tubes include avalanche photodiodes (APDs), single-photon avalanche diodes (SPADs), and silicon photomultipliers (SiPMs). These semiconductor-based sensors are superior in performance and much more compact and robust than the photomultiplier tubes. Although APDs, SPADs, and SiPMs are lower in cost than the photomultiplier tubes, they are still relatively expensive because they are only found in low-volume, niche applications.

With advancements in lidar technology for autonomous vehicles and robotics, which need powerful 3D range and depth sensing, the market for very sensitive detectors with low intrinsic noise and high photocurrents is growing. APDs and SiPMs are the most likely choices for 905-nm pulsed lasers to extend the sensing range of the lidar system because of their high intrinsic gain. The growing market for autonomous vehicles and the large number of sensors required for one vehicle will ultimately not only drive technology improvements, but also reduce cost. So autonomous driving technology could indirectly help cure cancer by driving down the price of flow cytometers through the replacement of photomultiplier tubes with newer sensors.

These advancements are helping to make flow cytometry tools smaller, more powerful, and more affordable, leading to countless new research opportunities for scientists. The future of cancer therapy could include customized analysis using flow cytometry to diagnose cancer stages and treat specific cancer types. The heterogeneity of cancer cells and their antibody responses are substantial and the immune response is complex. In the future, flow cytometry use could occur at the point of care with a tabletop or portable tool. Small, semicomplex flow cytometry devices may also be possible, with a cloud data link and AI-driven suggestions for sample preparation and appropriate antigens and fluorochromes for optimized results.

Meaningfully interpreting the readings from a large amount of available laser excitation wavelengths can be challenging. Software solutions have become a large portion of the size of the flow cytometry market, which is estimated to reach USD 8 billion by 2025. Despite these large market numbers, most of the actual tools are being used for research and development and not for point-of-care patients.

The current advancements in medical research, and in the diagnostic capabilities provided by flow cytometric technology provoke a shift in the flow cytometric business landscape. Instead of the technology being used only for research (with cumbersome, expensive tools), the market can be revolutionized by less complex tools that rely on cloud computing and AI to assist medical personnel in making diagnostic and therapeutic decisions for patients.

Outlook
Flow cytometry is a very powerful technology to phenotype and characterize cells on a single-cell level. Recent advances in technology have made the collection of flow cytometry data a daily routine, but consistent high-quality analysis and interpretation are still challenging. Given the collection of hundreds of thousands of events in minutes, the choice of the measured parameters, the gating strategy, and statistical analysis gives incredible opportunities but also bears certain risks. Flow cytometry data have to be further considered in the appropriate clinical context. Especially human datasets have to be handled with care as in some cases the homeostatic conditions are not well-defined, and normal patterns are not at all static. In addition, antigen expression can easily change during different types of treatments so that parameters, such as time after treatment, dosage, and basic patient characteristics need to be critically considered. This makes it extremely challenging to evaluate and judge data in a clinical and/or therapeutic setting.