Blood cell separating instruments are of great interest in many biomedical applications to discover a wealth of information about an individual's state of health. Selective isolation of cells by property or type from a heterogeneous mixture is the key enabler for a range of useful analysis including clinical diagnostics, monitoring, and therapeutics. Modern biomedicine also depends on the process of separating and isolating subpopulations of cells from a heterogeneous group. These diverse applications of selective cell isolation require high accuracy and reproducibility. The growing need of platelets and plasma attributing to rising blood-related disorders is promoting the demand for cell separators using high-performance technologies.
While technology is a driving force for the development of new techniques for clinical practice, it is not the only market force. For technology introduction, several other important issues need to be considered. Regulations at the local and, most importantly, the federal level impact the timing for new technology introduction. Reimbursement by healthcare payers is critically important from the initiation of the development of a technology through its clinical use. Clinical trials are critically important to show the safety and clinical- and cost-effectiveness of the technology in order for payers to provide reimbursement for its use, but these trials are sometimes long and costly. Research funding availability at the governmental and commercial levels critically impacts new technology investigation and its introduction. Apheresis technology developments offer new hopes and promises for the clinical team; however, their development, introduction, and utilization will be influenced by the prevailing market forces.
The global apheresis equipment market size was USD 1.89 billion in 2016 and is expected to exceed USD 4.5 billion by 2024, reflecting a CAGR of 11.4 percent, estimates Global Market Insights. The apheresis equipment industry is expected to be impacted by factors such as rising demand for plasma, platelets and other blood components, increasing incidence of chronic illnesses, presence and development of ideal reimbursement policies across various regions, and supportive government initiatives.
The US Federal Government has been very involved in the funding of apheresis research through its benefit programs such as Medicare, Medicaid, and veterans' health administration military and employee insurance programs. Medicare provides coverage for apheresis regardless of whether the procedure is performed in a hospital or a blood center. In addition, private insurers have recently begun to closely examine apheresis procedures and issue policy statements pertaining to coverage.
Growing incidence of blood-related disorders leading to the rise in demand for platelets and plasma is expected to serve the market as a high, impact rendering driver. The industry is also expected to be driven by technology innovations aimed at delivering relatively more effective and faster results. Healthcare practitioners and researchers are now in the need for devices requiring minimum human intervention and introduction of fully automatic apheresis equipment with enhanced displays is expected to improve usage rates.
Disposable apheresis kits are anticipated to dominate the product segment by 2024. Bulk volume purchase associated with these products is predicted to govern their growth. A single cycle of apheresis procedure consumes multiple disposable sub parts which is responsible for comparatively larger market volume as compared to apheresis machines.
The photopheresis procedure is anticipated to witness lucrative growth owing to its rising demand in treatment. The procedure is approved for treatment of solid organ transplant rejection, scleroderma, Type-I diabetes, pemphigus vulgaris, lichen planus and atopic dermatitis, and cutaneous T-cell lymphoma.
Another procedure expected to gain lucrative share is erythrocytapheresis. The procedure also finds application in blood donation procedures where it is widely used for separating two units of blood, known as double red cell apheresis. Rising incidence rates of genetic disorders such as sickle cell anemia is expected to drive market growth by widening the patient base.
Asia-Pacific is anticipated to witness the fastest growth over the next 8 years. Presence of high unmet needs and rapidly increasing demand for platelets in the emerging
Asia-Pacific and Latin American markets is expected to serve this market as future growth opportunities.
Key players include Fresenius Kabi; Haemonetics; Terumo BCT; Therakos, Inc.; Asahi Kasei Kuraray Medical Co Ltd; and B. Braun Melsungen AG. Strategies promoting faster distribution and development of efficient supply chain are being incorporated by the players.
The threat of new entrants in the apheresis equipment industry should be moderately high, due to a number of entry barriers such as high capital investment, licensing requirements, and sophisticated technical expertise for product development. Moreover, presence of unmet needs in emerging markets will encourage manufacturers to exploit these lucrative regions.
Understanding cellular heterogeneity has been a major thrust of technological development over the past decade, resulting in an increasingly powerful suite of instrumentation, protocols, and methods for isolating and separating cells. The new technologies and equipment enable selective isolation of cells using various cell properties like size, density, electrical properties, magnetic properties and acoustic properties, and have led to the development of efficient separation.
Continuous flow centrifuges. Conventional centrifuges involve a number of repeated tedious steps for processing large volumes of samples. They are labor-intensive and take up a significant amount of time. However, continuous-flow centrifuges allow processing of large volumes of material at high centrifugal forces without having to fill and decant a large number of centrifuge tubes or frequently stop and start the rotor, hence reducing material processing time. The combination of high throughput and high centrifugal force makes continuous flow processing useful for several applications.
FACS. Since its inception, remarkable advances have been made in the FACS instrumentation and the availability of a large number of highly specific antibodies. The capability of FACS technology has improved significantly from measuring 1–2 fluorescent species per cell to 10–15. Many fluorescence cell sorters now come with features such as temperature control, automated startup and cleanup, multiple lasers, and options for biosafety.
MACS. Rapidly growing demands for better cell separation methods in cell biology and clinical laboratories propelled magnetic cell separation to the forefront of laboratory preparative separation techniques. Magnetic cell-sorting instruments have become widely used, especially in separating and isolating cells from blood samples. They allow automated and parallel processing for better productivity and reproducibility. Their advantages include relative simplicity of operation, low capital investment, rapidly expanding selection of targeting antibodies, and magnetic tagging nanoparticles.
Microfluidics lab-on-chip devices. These devices circumvent several limitations of FACS through miniaturization such as high capital investment, high reagent consumption, binary separation, lysing of red blood cells to enhance capture efficiency, easy-handling of nanoliter samples, and cross contamination. Today, microfluidics can be combined with different separation methods, such as filtration and sedimentation or affinity-based technologies like FACS and MACS. Recently, microfluidic chips have been fabricated from silicon or glass, elastomer, thermosets, hydrogel, thermoplastics, and paper.
DACS. Dielectrophoretic (DEP) force has been used as a striking tool for biological particle manipulation or separation for the last few decades. Since a DACS does not require a specific bio-marker, it is able to function as a sorting tool with numerous configurations for various cells like RBCs, WBCs, circulating tumor cells, leukemia cells, and breast cancer cells. Over the years, DEP has finally made the transition to commercialization; there are now products becoming available to researchers that use DEP separation at their core, so that the use of DEP separation is no longer limited to those who understand how to build their own separator device. DEP devices so far failed to obtain throughputs comparable to existing, non-DEP cell separation technologies such as FACS and MACS. To overcome this, electrode designs have re-incorporated ideas with the reintroduction of electrodes extending into the 3rd dimension.
Challenges and Opportunities
In the present day scenario, apheresis procedures are preferred more over the traditional whole-blood collection and therapeutic methods. Growing concerns regarding blood safety and blood shortage, increased awareness regarding apheresis blood collection, growing aging population, increasing number of surgical procedures and emergency treatments, and rising demand for source plasma from biopharmaceutical companies are the key factors driving the worldwide apheresis market toward growth. In addition, penetration of apheresis in the unexplored pediatric sector and increasing investments from governments and leading market players, especially from emerging economies are expected to prospective growth opportunities for this market.
High costs of apheresis devices and procedures, lack of skilled and qualified doctors, and lack of knowledge regarding the apheresis process in the emerging and developing nations are the main reasons that may hamper the growth of this market. Also, lack of awareness and challenges in donor recruitment remains a key challenge being faced by the leading companies involved in this market.
There has been progressive improvement in apheresis equipment; still there is often competing tradeoffs between recovery rate, purity, throughput, and viability for approaches targeting a cell's property. Hybrid devices combining two or more principles for separating cells may be mutually complementary and overcome limitations of individual techniques. Hybrids are a promising approach to isolate multiple cell types by exploiting the benefits of multiple cellular properties in a single pass process.
Cell separation is only beginning to face the measurement challenges of cellular heterogeneity. There is still more room for improvement in enabling new modes of analysis and improving the sensitivity, precision, speed, and throughput of the separators. Considering the rapid progress in the development of cell separation, many of the problems currently being faced by the users will be solved in the near future.
Currently licensed automated apheresis equipment separates blood components by either centrifugation or filtration. The efficiency and the therapeutic applications of cell separator devices depend on the design of the equipment and the methodology used.
Differential centrifugation. This makes use of differences in density of various blood components. Mature red blood cells have the greatest density, while plasma has the least. The donor or patient blood is mixed with an anticoagulant and then pumped into a rotating bowl, chamber, or tubular rotor, and then whole blood is separated into layers of components based on density detected by sensors. In the intermittent-flow method, the centrifuge container is filled and emptied and the same venous line is used for both withdrawal and return of blood. This constitutes one cycle. The cycles are repeated till the desired quantity of the product is obtained.The major advantage is that it is one, arm procedure, hence convenient. In the continuous-flow method, two venous access sites are used, one for removal of the whole blood and the other for return of the unwanted portion back to the donor. The advantage of continuous-flow method is its speed and small extracorporeal volume.
Specialized procedures like photopheresis use buffy coat leucocytes treated with 8-methoxypsoralene and ultraviolet A radiation to be re-infused into the patient. This technique has been traditionally used in the treatment of cutaneous T cell lymphoma.
Filtration. Membrane-based blood separators are based on the differences in the actual size of particles. Platelets are the smallest particles while granulocytes are the largest. Filtration techniques have been developed for removal of a plasma constituent.Removal of low-density lipoproteins in familial hypercholesterolemia uses filtration technique.
Dr Swarupa Bhagwat,
Assistant Prof. in Blood Transfusion,
KEM Hospital Blood Bank, Mumbai
Current Apheresis Instruments Overview
The basic steps in any apheresis machine are separation of blood and removal of the desired components. This can be accomplished by filtration, centrifugation, or both. There are continuous flow centrifugation (CFC) and intermittent flow centrifugation (IFC) apheresis equipment. The current instruments available in The market are HeamoneticsMCS plus/ MCS, PCS PCS 2, Fenwal Amicus, Autoperesis C, Caridian BTC Cobe Spectra, Trima, Fresenious A104 and Comtec. Most of the instruments are CFC while Heamonetics, instruments are mostly IFC. Most of them can perform both single as well double needle.
Heamonetics apheresis equipment collects plasma, platelet, and red cell by IFC. The advantage of MCS and MCS Plus is its portability; disadvantage includes large extra corporeal volume, and long procedural time.
The FenwalAmicus advantage include reliable anticoagulant delivery, short collection time, low extra corporeal volume, easy loading, and short collection time.
Caridian BCT instruments have leukoreduction system; plate pheresis can be performed by both single and double needle and the operator communicates with the instrument through the control panel. Fresenius AS 104 and Comtec advantage include low extra corporeal volume, battery backup, and help program.
The current trend in deciding procurement of blood cell separator depends upon type of components your hospital generally requires, whether it is being required for plasma exchange or stem cell collection, low ECV, and portability.
Each instrument has advantage and disadvantages; however, due to market competition there are significant advances in blood cell separators.
Dr DS Rawat,
HOD Department of Transfusion Medicine,
Pushpawati Singhania Multi-specialty Hospital,
Sheikh Sarsai New Delhi,
Formerly Head Transfusion Medicine VMMC & Safdarjang Hospital, New Delhi
Use and Technology Selection
Aphaeresis is a term derived from Greek, meaning to carry away. This is the technique in which whole blood is taken away and separated extracorporealy, separating the portion desired from the remaining blood. This allows the desired portion plasma/platelets to be removed and the remainder returned to the donor.
Plateletpheresis. Platelet is separated from the whole blood, leaving behind the adequate number of platelets.
Plasmapheresis. Plasma is separated and removed (less than 15 percent of total plasma volume) without the use of replacement solution, such as colloid or combination of colloid/crystalloid. The replacement maintains intravascular volume, restoration of important plasma proteins, maintenance of colloid osmotic pressure, and maintenance of electrolyte balance.
Mechanism of action. A large-bore intravascular catheter/needle is connected to a spinning bowl. The whole blood is drawn from the donor into the centrifuge bowl. The high-density products like red cells settle at the bottom with less dense elements such as WBC, platelets overlying the RBC layer, and finally plasma at the top. The separate components are based on density with removal of desired components, the density of different blood components being platelets (1040), lymphocytes (1050–1061), monocytes (1065–1069), and granulocytes (1087–1092).
Technology. Automated centrifugal cell separator allows large volume of blood to be processed in a short period of time.
Use of apheresis procedure. The aphaeresis procedure is useful for donor program as it facilitates collection of blood components from allogeneic donor. It is also useful as a therapeutic mode in removing undesired substances like anti bodies (myasthenia gravis, good pastures syndrome) and lipids, reduce excess WBC, platelets, and automated exchange of sickled RBC. The frequency and number of procedures depends on disease being treated, patient's signs and symptoms, and lab reports.
Complications include hypotension, vasovagal syncope, hypocalcaemia, allergic reaction, hematoma, phlebitis, infection at venipuncture site, and air embolism.
Recommendation. The equipment should be fully automatic microprocessor controlled. It should have minimal extracorporeal volume. It should be easy to use for the staff and comfortable to the donor in a tertiary care hospital. It should have plasma exchange and mononuclear cell and PBS cell collection protocol.
Dr Bharat Singh ,
Consultant Pathologist and Head,
Regional Blood Transfusion Centre,
GTB Hospital and University College of Medical Sciences,
A Progressive Technology
An automated blood cell separator is a device that uses a centrifugal separation principle to automatically withdraw whole blood from a donor, separate it into blood components, collect the required blood components, and return the rest to the donor. The centrifugation method can be divided into two basic categories:
Continuous flow centrifugation. Continuous flow centrifugation require two venipunctures. Newer systems can use a single venipuncture. The main advantage of this system is the low extracorporeal used in the procedure, which may be advantageous in the elderly and for children.
Intermittent flow centrifugation. Intermittent flow centrifugation works in cycles, taking blood, processing it, and then giving back the unused parts to the donor. The main advantage is a single venipuncture site. To stop the blood from coagulating, anticoagulant is automatically mixed with the blood as it is pumped from the body into the apheresis machine.
On blood component collection
Plasmapheresis is useful in collecting plasma. Erythrocytapheresis is the separation of red blood cells from whole blood. Method of centrifugal sedimentation is used for this process. Plateletpheresis is collection of platelets. The yield is 3.01011 in number and it is equivalent of between six and ten random platelet concentrates. The shelf life is 5 days. Leukapheresis is the removal of white cells, and transfusing into patients who lack these cells. They have a very short shelf life (24 hours at 20
On therapeutic use
Whenever any constituent is causing severe symptoms of disease.
Plasma exchange – removal of plasma to remove harmful substances.
LDL apheresis – removal of low density lipoprotein in patients with familial hypercholesterolemia.
Photopheresis – to treat graft-versus-host disease, cutaneous T-cell lymphoma, and rejection in heart transplantation.
Immunoadsorbtion– removal of antibodies (in autoimmune diseases, transplant rejection, hemophilia)
Leukocytapheresis – removal of malignant white blood cells in people with leukemia and very high white blood cell counts causing symptoms.
Erythrocytapheresis – removal of red blood cells in people with iron overload.
Thrombocytapheresis – removal of platelets in people with symptoms from extreme elevations in platelet count.
Cell separation for any indication is done using single-use kits hence no risk of infection.
Chief Medical Officer,
Rotary Blood Bank, New Delhi
Transfusion Technology Trends
Cell separators are used for apheresis procedures wherein single or more than one component is collected and rest are returned back. The working principle is centrifugation (most commonly used) or filtration. They can be continuous flow centrifuge or intermittent flow. There are three areas of application Donate blood cells for transfusion eg. for treating coagulation dysfunctions or leukemia patients; Remove cancer cells eg. leukemia or autoimmune disease patients; and collect patient's cells eg. patient's own blood for re-infusion prior to operation.
On technology trends
Today product development continues to focus on innovative technologies and automation. Apheresis procedures available are plateletpheresis, plasmapheresis, erythrocytapheresis, leukapheresis, stem cell harvesting, LDL apheresis, and photogpheresis. New-generation cell separators have the option of single-or double-venous access.
On buyer's perspective
A buyer looks for reliability, ease of use, low maintenance/operating costs, price, safety features, accuracy, service support and ease of installation. Buyer chooses a model that suits the need not only today but for years to come and also gives full comfort reliability and hassle free experience for blood donors.
On key growth drivers
Growing population, increasing rate of sickness, blood demand, public awareness, advantages of apheresis over whole blood donation, advancing and improving healthcare infrastructure, and government support are major drivers that propel the market.
On challenges and opportunities
Technology and international entrants in the Indian market, motivation to be at par, consolidation among end-users, high purchasing power, awareness toward product innovation, pricing policies, and judicious use of components are major challenges.
Emerging, pathogens, increasing population after-sales-service trained staff provided by manufacturer and researcher provide opportunities for growth.
On future outlook
A significant outlook lies in future resulting from stringent regulations, public awareness, advances in diagnostics, IT engineering systems, automation, and competition. Interaction between blood bankers and clinicians and government support give promise for movement toward goal for a safe blood supply.
We at our hospital look forward to invest in the best of instruments making use of latest technology, follow regulatory and quality protocols, and strive to strengthen the donors' and patients' confidence in blood transfusion services.
Dr Puja Pandey,
Blood Bank Incharge,
The B.D.Petit Parsee General Hospital, Mumbai