Blood separators-Solving the diagnostic mystery

Rapid technological advancements are leading to the development of next-generation apheresis devices that promise to reduce human intervention and provide results faster and more effectively.

The first introduction of equipment to perform apheresis procedures was in blood transfusion centers as they held responsibility for supplying blood products for transfusion to patients, and the development of apheresis equipment was primarily to obtain blood components for transfusion. The collection of blood components for transfusion led to development of apheresis units outside the blood transfusion center to meet demands for blood components. Blood also contains massive information about the functioning and status of the body, making separation of blood cells a requisite and critical step in many research applications and therapeutics. Current methods for blood cell separation require complex and expensive equipment. Centrifugation, the gold standard and the most common method for blood cell separation, is labor-, energy-, and time-intensive and relies on well-trained operators. To address the limitations of conventional, centrifugation-based blood processing, several groups have explored alternative technologies, such as hollow fiber filtration that is capable of extracting RBC products from whole blood, with minimal labor or equipment requirements, but requires relatively expensive membranes; single-stage microfluidic arrays have typically been able to handle very dilute blood samples; and devices employing fluorescence-activated cell sorting (FACS) or magnetic separation (MACS) can sort up to 50,000 cells per second, with higher rates achievable at the cost of purity.

Market players are presenting shrewd stage plans that fuse, for example, particular hemoperfusion, twofold filtration with adsorption, plasma trade, and twofold filtration which helps blood refinement solutions. Additionally, players are making propelled gadgets that have mechanization features and are outlining propelled equipment that have computerization highlights, and these apparatuses have broad request in national blood transfusion focuses. The developing acknowledgment of dispensable apheresis packs because of their generally low costs has made bounteous open doors for little producers.

Indian scenario
With several road accidents occurring every day, millions of surgeries and major operations being performed every year, rising cancer-related procedures like chemotherapy, and increasing pregnancy complications, all require a serious call for transfusion of blood and blood products. Thus, a well-organized blood transfusion service (BTS) is a vital component of any healthcare delivery system, and ensuring the safety and availability of blood and blood products is an essential public health responsibility. The BTS in India is highly decentralized and lacks many vital resources like skilled manpower, adequate infrastructure, and a strong financial base. The blood component production/availability and utilization is extremely limited. For quality, safety, and efficacy of blood and blood products, well-equipped blood centers with adequate infrastructure and trained manpower is an essential requirement. A major problem plaguing blood banks in India is poor monitoring and control because of the multiplicity of agencies involved. Consistent quality and safety in the provision and administration of blood and blood products cannot be achieved without a coordinated service with an appropriate national blood policy.

National Blood Transfusion Council (NBTC), the apex policy-making body for issues pertaining to blood and plasma is a part of the National AIDS Control Organization (NACO). NACO supports a network of over 1100 blood banks across the country and strives to achieve accessibility to an adequate quantity of safe, quality, and affordable blood and blood components to the needy. NACO, through different phases of National AIDS Control Program (NACP), supports the establishment of component-separation facilities and also funds modernization of all major government and charitable blood banks at state and district levels. In order to promote rational use of blood, blood component separation units (BCSU) are being established and NACO support is extended to several BCSUs across the country. These BCSUs are working in their respective states and the proportion of blood units processed for component separation has risen since the launch of NACP.

New principles of safe handling, cost, and administration of blood components have an impact on blood safety with the growing concern for apt utilization of blood products. Without blood or blood-products transfusion, effective management of severe trauma, major elective surgery, and serious obstetric complications, is not possible, as it is an essential part of the infrastructure. NACO is working hard to improve BTS in the country, but there is still no national blood law. In the absence of a legal authority empowered by the national blood law, optimal quality of BTS will remain a mirage in the country.

Global market
The global apheresis equipment market is projected to reach USD 3.1 billion by 2025, driven by the growth in global blood demand as well as supply against a backdrop of aging population and rising prevalence of diseases requiring blood transfusion. The life-saving importance of blood can be put into perspective by the fact that it is the only biological product of ubiquitous importance in surgical theaters and ICUs.

The global demand for blood continues to increase, the magnitude of which can be best illustrated by the fact that cancer treatment needs 8 units of blood per patient per procedure, coronary artery bypass surgery requires 5 units of blood, while organ transplants need 10 units of blood. With 18 million new cancer cases diagnosed worldwide every year, with North America alone expected to witness over 470,000 cardiovascular surgeries by 2021 and global CVD mortality rising to 17 million each year and with over 100,000 solid organ transplants are performed each year worldwide, the importance of global need for safe blood cannot be undermined.

The rising demand for plasma, platelets, and other blood components is throwing the focus on equipment designed for selective isolation of blood components. The scenario provides a fertile environment for the growth of blood collection and processing equipment. Growing concerns over contaminated blood with HIV & Hepatitis is driving investment resources into the development of automated apheresis equipment which requires minimal human contact and intervention.

With the increasing number of surgeries and surgical techniques, advanced treatments have led to a global demand for blood and blood components. The need for blood components is significantly growing and contributing to healthcare spending. Apheresis has also recently witnessed a high demand due to an increased number of patients suffering from various ailments related to kidney, metabolic diseases, and neurological disorders. Therefore, apheresis technology is used to reduce the number of white cells, until other medications can control them. With the steady increase in the number of patients suffering from these diseases, ailments, and the technical ease of using these devices in the treatment of these diseases, requiring a minimal hospital stay, the global apheresis market is poised to experience growth during 2019–2023. The use of apheresis in clinically ill patients is increasing day by day, and it has been widely used as the primary therapy or as an adjunct to other treatments for various diseases, such as thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, drug toxicities, autoimmune disease, sepsis, and fulminant hepatic failure.

By product segment, disposables and reagents segment generated the highest revenue in 2019 and is anticipated to maintain its dominance over the next 5 years. In addition, disposable segment is estimated to register the highest growth rate from 2020 to 2025, with extensive advancements that are taking place in the manufacturing of blood bags, tubing, and disposable kits. Disposable kits, which include filters, separators, tubing set, blood bags, and other disposables, are utilized on a large-scale during processing of blood. Other disposables include anticoagulants, reagents, and small components associated with tubing assemblies.

Centrifugation method accounted for the highest revenue in 2019, and is expected to maintain its dominance in coming years. This is attributed to the predominant use of centrifugation in the preparation of blood components such as packed red blood cells (PRBCs) and fresh frozen plasma (FFP) in a single-step heavy spin. Membrane separation is anticipated to register the highest CAGR, as membrane filters play a pivotal role in filtration of plasma from other cellular components to achieve specific cell separation.

Region wise, North America dominated the market in 2019, accounting for highest share, and is anticipated to maintain this trend. However, Asia-Pacific is projected to register the highest growth rate from 2020 to 2025.

The competition in global apheresis market is expected to grow notably due to the advent of leading players in the forthcoming years. To sustain their market position and improve their global reach, the firms are concentrating on strategies like mergers and acquisitions and collaborations. Some of the key players operating in the global apheresis market include Haemonetics Corporation, Fresenius Kabi, Terumo BCT, Inc., Asahi Kasei Medical Co., Ltd., HemaCare Corporation, Kaneka Corporation, Kawasumi Laboratories Inc., Cerus Corporation, B. Braun Melsungen AG, and Nikkiso Co., Ltd.

Technological advances
The new technologies in cell separation have evolved significantly from the cumbersome and crude age-old technologies. There are several centrifuge-free options of blood cell separators presently available in the market.

Dielectrophoresis (DEP) has been demonstrated as an effective mechanism for cell sorting in microfluidic settings. Many existing methods utilize sophisticated microfluidic designs that require complicated fabrication process and operations. Using a simple array of indium-tin oxide (ITO) electrodes to generate DEP force field, the cells of interest are hydrodynamically separated from the blood. It causes cell separation to be done 10,000 times faster. Improving the ability to separate particles and cells in a continuous flow pattern facilitates faster and incessant medical diagnosis. Thanks to the new design of these cell separators, they can be used in vital therapies for life-threatening diseases, can be carried out at a fraction of the usual cost, and can be used for therapeutic as well as research purposes.

Membrane filtration technology presents an attractive alternative to centrifugation-based cell separation since filtration systems are significantly simpler and less expensive. Recent developments in microfiltration utilize membranes for the absorption of unwanted solutes and cells present in the blood. Filtration using spinning membrane is another method used for blood cell fractionation. Spinning membrane separators provide excellent filtration rates by generating Taylor vortices in the gap between the membrane and the shell of the device. This unique flow pattern creates flow at the membrane, constantly sweeping the surface to prevent the cellular components from depositing on and clogging or fouling the membrane, while continually replenishing the medium to be filtered.

Acoustic cell separation device can manipulate thousands of cells, separating the tumor cells from the blood cells or specific blood cells from whole blood, based on their significant difference in size, compressibility, and other physical properties, by exposing them to sound waves while flowing through the microchannel. It offers a unique approach for researchers in bioengineering projects and clinical diagnosis. Separating the cells with sound offers a gentler alternative to the existing cell sorting techniques, which requires the labeling cells with antibodies or exposing them to stronger mechanical forces that may damage the cells. This platform uses an integration of three modules of microfluidic platforms, which consist of a high-throughput separation, cell spatial organization and cell staining, imaging, and quantification analysis. This platform combines the isolation and evaluation steps toward rare cancer cell sorting and identification.

Way forward
Latest advances in cell biology, disease diagnostics, and medicine have increased the demand in rapid, safe, and accurate cell sorting and manipulation devices. Microfluidic devices are at the center of attention due to low sample and reagent volume requirement, portability, ability to work on a single cell scale level, and self-contained nature allowing safer handling of hazardous liquids and materials. Despite the advantages of performing cell analysis, sorting, and manipulation in a microfluidic chip, they still have a number of limitations that prevent standardization for clinical use and wide commercialization. Among these are device throughput, lifespan, multipart manufacturing, and ease of handling.

Multimodal, parallel integration of microfluidics with active sorting and manipulation methods is a promising approach to overcoming these limitations. Magnetic, electric, acoustic, and optical forces can be harnessed to cater to a wide spectrum of applications.

Moreover, optical forces can be applied from the outside of the microfluidic device, thus allowing development of highly modular, multi-purpose systems for cell sorting and manipulation. Optical forces offer more interaction freedom, which can be adjusted in real-time. Further investigation and development of novel techniques utilizing optical forces might prove to be a stepping stone toward development of state-of-the-art lab-on-a-chip devices.

Rapid technological advancements are leading to the development of next-generation apheresis devices with automated interface systems, screen navigation, and graphical user interface displays that will reduce human intervention and provide results faster and more effectively. Technology vendors – specifically digital companies – can play a larger role in enhancing apheresis product features.