The purpose of transfusion diagnostics is to ensure the safety of the blood supply. It has two components, the screening of blood donations and patient samples to ensure compatibility of blood group before transfusion, and the screening of blood donations for known pathogens to prevent transmission of infectious agents. The global transfusion diagnostics market is large and established. Total annual product sales in this market amounted to $2.8 billion in 2011, of which $1.3 billion occurred within the United States. We believe nearly two-thirds of testing occurs in the highly concentrated donor testing market, while the remaining third occurs in the much more fragmented hospital setting.
We have designed MosaiQ™ leveraging our 30 years of transfusion diagnostics expertise. MosaiQ™ combines novel manufacturing techniques and well-characterized blood grouping and disease screening tests to create a multiplex testing consumable for use on a high-throughput instrument. Through miniaturization, we are combining a full portfolio of existing serological tests on two distinct consumables for use on MosaiQ™ – one for blood grouping and one for serological disease screening. Both consumables have been designed to run in parallel, utilizing the same donor sample and the same MosaiQ® instrument. Each consumable is designed to address the worldwide requirements for blood grouping or serological disease screening.
Specifically, we are developing MosaiQ™ to simultaneously:
- Determine the full antigen profile of patient and donor red blood cells and identify all clinically significant antibodies in patient and donor plasma (Blood Grouping); and
- Serologically screen donor blood for specific viruses (Disease Screening).
Prior to blood transfusion, or when there is likelihood that a blood transfusion might be required, extensive blood grouping procedures are undertaken on patient and donor blood using in vitro diagnostic products. These procedures ascertain the blood group of the patient and ensure the compatibility of donor blood. The testing regime is designed to prevent transfusion reactions, which can range from mild to fatal.
Red blood cells (the cellular portion) and plasma (the fluid portion) are the principal components of blood. On the exterior of red blood cells are antigens that determine an individual’s blood group (A, B, AB, O), or ABO group, and type (RhD positive or RhD negative), or Rh type. In addition, there are at least another 32 clinically significant blood-group antigens that may be present on patient and donor red blood cells. Plasma contains many different kinds of proteins, including: (i) naturally occurring blood-group antibodies; (ii) blood-group antibodies developed by the body in response to foreign red blood cell antigens introduced during transfusion (allo-antibodies); or (iii) blood-group antibodies developed following pregnancy. Blood-group antibodies mirror the antigen families that are present on red blood cells. In its normal state, blood does not contain antibodies that will react with its own red blood cell antigens (auto-antibodies).
Because of the potential for a reaction of blood-group antigens and antibodies, it is crucial that clinicians correctly identify the blood-group antigens or antibodies present in donor and patient blood before transfusion. If a donor’s red blood cells contain antigens that are recognized by and react with existing blood-group antibodies in the patient’s plasma, the transfused red blood cells could be destroyed in a potentially life-threatening reaction. The identification of blood-group antigens on donor and patient red blood cells is typically referred to as blood typing or basic antigen typing, with a more comprehensive characterization being referred to as extended antigen typing. The identification of blood group antibodies in plasma is typically referred to as antibody identification.
All patients potentially requiring a blood transfusion will generally be blood grouped, including pregnant women, cancer patients undergoing chemotherapy, patients undergoing surgery or patients suffering from chronic diseases that require regular blood transfusions, such as thalassemia or sickle cell disease.
Techniques used for Blood Grouping have remained relatively unchanged for many years. Instrument platforms allowing limited automation have been introduced, however they still require significant manual intervention in approximately 5-10% of cases to undertake extended Blood Typing (or phenotyping) or a full Antibody-ID. A significant proportion of the cost of Blood Grouping is accounted for by the ongoing requirement for manual testing.
With the importance of Blood Grouping and the limitations of existing instrument platforms, highly skilled and educated blood banking technologists are required to support the blood testing needs of hospitals, donor centers and reference laboratories. Additionally, with over 50 clinically significant antigens and antibodies to characterize, the liquid reagent requirements for blood grouping (whether performed on instruments or manually) are both complex and extensive. Conventional reagents also have limited shelf lives (as low as 28 days in the case of red cell products) and can, individually, be very expensive.
The importance of timely Blood Grouping and the limitations of existing instrument platforms (requiring significant manual intervention) has also restricted the use of existing instrument platforms in smaller patient testing settings.
The safety of donor blood is ultimately the responsibility of donor collection agencies, with regulatory agencies in individual countries establishing safeguards and standards to ensure patient safety. In the developed world, donor blood is subject to mandatory screening for infectious diseases before it can be released to hospitals. Two different methods of testing have been adopted – a serological approach (testing for specific antigens or antibodies) and, for certain viruses, a molecular approach (testing for nucleic acid). The United States, many countries in Western Europe and Japan require both serological and molecular disease screening be performed on donor blood. In the United States, it is mandatory to screen donor blood using serological techniques for the following: Syphilis, Hepatitis B Surface Antigen, Hepatitis B Core Antibody, Hepatitis C Antibody, Human Immunodeficiency Viruses, or HIV, Type 1 and Type 2 Antibodies and Human T-Lymphotropic Antibodies. Most blood collection agencies will also screen for Cytomegalovirus, or CMV, using the same serological approach and the FDA recommends donor blood to be screened for Chagas disease. Molecular disease screening is required to be performed on donated blood to screen for Hepatitis B, Hepatitis C, HIV and West Nile virus. Other pathogens, such as Babesia Microti, Dengue and Malaria are transmissible by blood, but there is no test currently available, given cost or technology limitations.
Serological disease screening is already largely automated, with current testing typically performed on two separate instrument platforms offered by different vendors.
Donor & Patient Testing Environments
Blood grouping and disease screening techniques have remained generally unchanged for many years, with a handful of instrument platforms available for basic antigen typing, antibody screening and some additional antigen typing. However, significant manual intervention is still required to complete more complex blood grouping procedures, such as extended antigen typing and antibody identification. In many cases, it is also not possible to obtain a sufficient blood sample volume from patients (for example, from anemia patients and babies) for blood grouping using existing instrument platforms.
Limitations of Current Blood Grouping and Disease Screening Methods
A significant proportion of the overall cost of blood grouping is accounted for by the ongoing need for complex manual testing procedures. Additionally, with over 30 clinically significant blood-group antigens and antibodies to characterize, the required reagents for blood grouping (whether performed on instruments or manually) are both complex and extensive.
We believe both donor collection agencies and hospitals would prefer to fully characterize donor units through extended antigen typing prior to transfusion, although the time and expense required to undertake such procedures is generally prohibitive. As a consequence, extended antigen typing is only undertaken as needed (i.e., where the patient has a specific antibody) on a small percentage of donor units.
Existing blood grouping methods and instruments have a number of additional drawbacks, including:
- Extensive antigen typing is not widely undertaken pre-transfusion due to cost and complexity, resulting in more patients developing antibodies, which complicates future transfusions;
- Requirement for highly trained laboratory technicians;
- Extensive, complex and expensive reagent requirements, some with shelf lives under 30 days;
- Supply shortages of licensed antisera for some rare, but clinically significant blood-group antigens;
- Incremental supervision, technical training and quality assurance costs, given the lack of standardization resulting from complex manual testing procedures;
- Potential for testing or labeling errors given the large manual component;
- Lower red blood cell or plasma yields for donor collection agencies, given test volume requirements;
- Difficulty testing patients that can provide only low volumes of blood samples, including anemia patients and babies;
- Costly service and support infrastructure needed to maintain multiple instrument platforms in a donor testing environment; and
- Inability of existing instrument platforms to connect to laboratory automation (or track-based) systems.
Serological disease screening is already largely automated. However, it is typically undertaken using two separate instrument platforms, neither of which is integrated with commonly used blood grouping instruments. Automation platforms for serological disease screening have been on the market for many years but lack many of the attributes users benefit from in other diagnostic fields such as user-interface, remote diagnostics, ability to link to laboratory automation systems and software compatibility with laboratory information systems. Additionally, existing disease screening platforms lack the ability to easily add additional tests as the market and regulators dictate.
The MosaiQ Solution
We are developing MosaiQ™ to address the comprehensive needs of the global transfusion diagnostics market. We believe MosaiQ™ has the potential to transform transfusion diagnostics by substantially reducing costs and offering a range of operational efficiencies within donor and patient testing laboratories, while improving patient outcomes through a more complete characterization of donor and patient blood.
MosaiQ™ will comprise two separate consumables, one for blood grouping and one for serological disease screening, and initially, a high-throughput instrument. In a donor testing environment, MosaiQ™ is designed to conduct both blood grouping and disease screening tests simultaneously, while only blood grouping would be performed in a patient testing environment. The MosaiQ™ blood grouping consumable will consist of two protein microarrays: one printed with red blood cells and the other printed with antibodies. Our novel approach incorporates existing, well-characterized tests for all clinically significant blood-group antigens and antibodies onto a single, multiplex consumable for the global market. Using the same approach, we plan to incorporate all currently mandated serological disease screening tests onto a second disease screening consumable. Both consumables are designed to be processed using the same MosaiQ™ high-throughput instrument.
Blood Grouping Consumable
The MosaiQ™ blood grouping consumable is designed to fully characterize donor and patient blood, identifying all clinically significant blood-group antigens and antibodies. We believe MosaiQ™, when launched, will be the only commercially available automation platform capable of offering this scope of testing.
Click here to see the tests we plan to incorporate on the blood grouping consumable.
Disease Screening Consumable
The disease screening consumable is being designed to incorporate all tests required to meet current regulatory requirements in the markets in which we operate for serological disease screening of donor blood. We are including tests to screen serologically for Syphilis, Hepatitis B Surface Antigen, Hepatitis B Core Antibody, Hepatitis C Antibody, HIV Type 1 and Type 2 and Human T-Lymphotropic Antibodies Type I/II, along with a test for CMV. The disease screening consumable has been specifically designed with the capacity to include additional disease screening tests as may be mandated by regulatory requirements.
The MosaiQ™ instrument is designed to fully automate blood grouping and perform a simultaneous disease screen in a donor testing laboratory. Consistent with the typical workflow of donor or patient testing laboratories, centrifuged tubes of whole blood will be placed on the MosaiQ™ instrument for processing. The instrument will then complete a full blood group characterization of each blood sample, combined with a parallel disease screen in a donor testing environment, with the results being reported through existing laboratory information management systems (or LIMS).
We are developing a high-throughput, floor standing MosaiQ™ instrument for use by both donor collection agencies and medium to large-sized hospitals. This initial MosaiQ™ instrument is being designed to process 900 to 1,000 consumables per eight-hour shift, giving a capacity to test 450 to 500 donor samples (utilizing a blood-grouping consumable and a disease screening consumable) or 900 to 1,000 patient samples (blood grouping only).
We expect the use of MosaiQ™ for blood grouping and disease screening will offer both major cost saving opportunities and clinical benefits, including:
- Improved clinical decision making and better matching of donor and patient blood, with the potential to reduce the incidence of alloimmunization;
- Extended antigen typing for all donor blood;
- Comprehensive antibody identification, eliminating the need for an antibody screen and expensive manual testing;
- Significantly reduced need for complex, manual testing procedures, delivering major workflow efficiencies;
- Standardization of blood grouping, reducing the potential for testing or labeling errors;
- Consolidation of multiple instrument platforms and complicated manual testing procedures onto a single automated instrument;
- Significantly simplified consumable requirements, with one consumable for blood grouping and one consumable for disease screening;
- Substantially improved time to result for complex blood grouping procedures, such as antibody identification and extended antigen typing;
- Significantly lower donor testing volume requirements, increasing plasma and red blood cell yields per donation;
- Lower patient sample volume requirements, potentially eliminating the need for manual testing where sufficient sample volume proves difficult to obtain (for example, from babies and patients suffering from anemia);
- Significantly increased shelf life for red blood cell-derived tests;
- Reduced consumable waste;
- Lower sample logistics costs;
- Potential to electronically match donor and patient blood; and
- Ability to integrate onto existing laboratory automation (track-based) systems.
MosaiQ Validation To Date
We have conducted extensive feasibility work internally to demonstrate the performance of the MosaiQ™ methodology compared with predicate technologies for specific antigen typing and antibody identification tests to be included on the MosaiQ™ blood-grouping consumable. This work focused on demonstrating specificity of the antigen typing tests for key blood group systems (ABO, Rh and Kell) and the specificity and sensitivity of the antibody identification assay. We designed these studies to evaluate the MosaiQ™ methodology with a large data set and direct our future development efforts.
Click here for our latest testing results.
- ABO and Rh Antigen Typing of Red Blood Cells Using a Novel Serology-Based Multiplexed Protein Microarray Platform (Project MosaiQ). Robb, JS, Knowles, LK, and Robson, DC. AABB Annual Meeting 2013
- Evaluation of a Novel Serology-Based Platform for Irregular Blood Group Antibody Identification (Project MosaiQ). Robb, JS, Renault, NK, and Robson, DC. AABB Annual Meeting 2013