Celloscope automated cell counter was developed in the 50s for enumeration of erythrocytes, leukocytes, and thrombocytes in blood samples. [1] Together with the Coulter counter, the Celloscope analyzer can be considered one of the predecessors of today's automated hematology analyzers, as the principle of the electrical impedance method is still utilized in cell counters installed in clinical laboratories around the world. [2] [3]
The Celloscope was developed for the Swedish company AB Lars Ljungberg & Co under the direction of engineer Erik Öhlin at Linson Instrument AB. [4] In an interview published in the Clinical Biochemistry in the Nordics, a membership magazine for the Nordic Association for Clinical Chemistry, Lars Ljungberg explains that he and his coworkers had been considering different solutions for counting blood cells for some time when they came across a method presented by the American Navy on how particles could be counted when allowed to pass a capillary hole through which a weak direct current was passed simultaneously. [5] [6] The Celloscope method exploits the feature of blood cells not being conductive and therefore make interruptions (pulses) to the current, which then can be counted. [7] What Ljungberg and coworkers did not know was that Wallace H. Coulter in Chicago had applied for and received a patent on the particle count principle in 1953. [8] When presented at a German tradeshow in September 1957, the Celloscope counter was examined by Dr. George Brecher, the first author of one of the NIH evaluations of the Coulter counter. [9] In a letter to Coulter, Brecher reported about what he thought was a close functional copy of the Coulter counter, yet with simpler electronics and an integrated sample stand, creating a both smaller and less costly instrument for use in clinical applications. [9] When the Celloscope was introduced to the market in the early 60s, a lawsuit was filed by Coulter Electronics Inc against AB Lars Ljungberg & Co for alleged infringement of the American patent. [10] After many and long negotiations, the companies came to the agreement to compensate Coulter for the sales that had been made in USA and some European countries where he had the patent and that AB Lars Ljungberg & Co was free to sell their analyzer in other regions. [9] [6]
Before the introduction of the first automated cell counters, hematologists were referred to manual cell count under the microscope. [2] [11] The Celloscope method for automated counting of blood cells was described in an article by Öhlin in 1958. [1] [12] In the described method, cells in a saline (conductive) solution are allowed to pass through a capillary with a length and diameter corresponding to the size of blood cells. At the same time, an electric current passes the capillary, and each cell then gives rise to an electric pulse through the increase in resistance that it causes in the electric circuit. The number of pulses is recorded and corresponds to the number of cells in a certain volume. Diluting the blood sample to a sufficient extent for the distance between the cells when passing through the capillary to be greater than the dimension of the cells and capillary ensures that each cell is counted individually. As cells are counted in an absolute volume of the suspension, the number of cells in mm3 of whole blood can be calculated using the dilution factor. The described automated Celloscope cell count method enabled an improved accuracy compared with manual examination by microscopy, while decreasing manual work for the operator. The method allows 50 000 cells to be counted in about 45 seconds, with high accuracy. The Celloscope counter was also equipped with a discriminator, or electrical threshold, which allows only pulses above a certain size to be counted, enabling different blood cells to be counted. For example, set to a threshold of 3 μm, all cells are counted. A re-count at a threshold of 4 μm allows calculation of the number of cells of a size between 3 and 4 μm from the total counts. Diluting the blood sample 1/80 000 in a physiological saline solution allows enumeration of the erythrocytes, as the number of leukocytes does not affect the result more than by about 1/1 000 000. For the leukocyte count, cells in the same sample are hemolyzed with saponin or cetrimide so that only the nuclei of the leukocytes are counted. [6] [13] [14] For platelet count, a smaller capillary diameter is used. To identify cell morphologies and variants that the counter cannot detect, microscopy remains an essential complement to the automated cell count method. [15]
The impedance method used in the Celloscope analyzer has been further developed to allow counting also of leukocyte subgroups. [2] [3] In addition to the cell counts, modern hematology analyzers are also capable of reporting parameters related to cell size, hemoglobin concentration, as well as a range of calculated parameters, for a complete blood count (CBC). These analyzers were initially intended to be used in hospital laboratories, as they required a skilled staff and a high sample load to justify their relatively high cost, however, with the increasing need for decentralized healthcare, the demand for simpler analyzers emerged and prompted the development of benchtop cell counters that could be used in a near-patient clinical setting with a minimum of training. [2] [16] [17] In 1969, Erik Öhlin founded Swelab Instrument AB (today, Boule Medical AB [18] ), and later, the Swelab AutoCounter AC-series was launched to meet the needs of the smaller clinical laboratories.
The cell counters of that time used LED screens for result review. In 1982, Medonic AB, another Swedish company with focus on hematology, was founded. [19] The founders, Ingemar Berndtsson and Abraham Bottema, both had a long history and experience in hematology, clinical chemistry, and blood banking engineering. [20] [21] [22] In 1985, Medonic AB launched the Cellanalyzer CA 480 system, its first own-developed cell counter with a built-in display that also showed the cell histograms. [23] When computers began to be incorporated into the analyzers, other brands, like the Swelab analyzers, also came with a display. Both targeting the smaller clinical laboratories, Swelab Instrument AB and Medonic AB were competitors on the decentralized hematology testing market. [24] [25] [26] In the late 90s, both Swelab Instrument AB and Medonic AB were acquired by Boule Diagnostics AB. [27] [28] The company has kept the parallel brands and the analyzers are still manufactured from its facilities in Stockholm, Sweden and supplied under the Swelab and Medonic trademarks for the decentralized hematology testing market. [29] [30] [31] [32] [33] [34]
When Coulter was acquired by Beckman, former Coulter employees Dr. Harold R Crews, Andrew C Swanson, and Donald Grantham founded Clinical Diagnostic Solutions, Inc. (CDS) in 1997, focusing on the development and production of generic reagents and control material. In 2004, CDS was acquired by Boule. By this acquisition, Boule came to master the skills of the development and production of both instruments and the consumables included in a complete hematology system.
Microfluidics refers to a system that manipulates a small amount of fluids using small channels with sizes of ten to hundreds of micrometres. It is a multidisciplinary field that involves molecular analysis, molecular biology, and microelectronics. It has practical applications in the design of systems that process low volumes of fluids to achieve multiplexing, automation, and high-throughput screening. Microfluidics emerged in the beginning of the 1980s and is used in the development of inkjet printheads, DNA chips, lab-on-a-chip technology, micro-propulsion, and micro-thermal technologies.
Clinical chemistry is a division in medical laboratory sciences focusing on qualitative tests of important compounds, referred to as analytes or markers, in bodily fluids and tissues using analytical techniques and specialized instruments. This interdisciplinary field includes knowledge from medicine, biology, chemistry, biomedical engineering, informatics, and an applied form of biochemistry.
A blood cell is a cell produced through hematopoiesis and found mainly in the blood. Major types of blood cells include red blood cells (erythrocytes), white blood cells (leukocytes), and platelets (thrombocytes). Together, these three kinds of blood cells add up to a total 45% of the blood tissue by volume, with the remaining 55% of the volume composed of plasma, the liquid component of blood.
Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but which contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. It is the intravascular part of extracellular fluid. It is mostly water, and contains important dissolved proteins, glucose, clotting factors, electrolytes, hormones, carbon dioxide, and oxygen. It plays a vital role in an intravascular osmotic effect that keeps electrolyte concentration balanced and protects the body from infection and other blood-related disorders.
A complete blood count (CBC), also known as a full blood count (FBC), is a set of medical laboratory tests that provide information about the cells in a person's blood. The CBC indicates the counts of white blood cells, red blood cells and platelets, the concentration of hemoglobin, and the hematocrit. The red blood cell indices, which indicate the average size and hemoglobin content of red blood cells, are also reported, and a white blood cell differential, which counts the different types of white blood cells, may be included.
An automated analyser is a medical laboratory instrument designed to measure various substances and other characteristics in a number of biological samples quickly, with minimal human assistance. These measured properties of blood and other fluids may be useful in the diagnosis of disease.
The hematocrit, also known by several other names, is the volume percentage (vol%) of red blood cells (RBCs) in blood, measured as part of a blood test. The measurement depends on the number and size of red blood cells. It is normally 40.7–50.3% for males and 36.1–44.3% for females. It is a part of a person's complete blood count results, along with hemoglobin concentration, white blood cell count and platelet count.
A blood smear, peripheral blood smear or blood film is a thin layer of blood smeared on a glass microscope slide and then stained in such a way as to allow the various blood cells to be examined microscopically. Blood smears are examined in the investigation of hematological (blood) disorders and are routinely employed to look for blood parasites, such as those of malaria and filariasis.
An assay is an investigative (analytic) procedure in laboratory medicine, mining, pharmacology, environmental biology and molecular biology for qualitatively assessing or quantitatively measuring the presence, amount, or functional activity of a target entity. The measured entity is often called the analyte, the measurand, or the target of the assay. The analyte can be a drug, biochemical substance, chemical element or compound, or cell in an organism or organic sample. An assay usually aims to measure an analyte's intensive property and express it in the relevant measurement unit.
In hematology, thrombocythemia is a condition of high platelet (thrombocyte) count in the blood. Normal count is in the range of 150×109 to 450×109 platelets per liter of blood, but investigation is typically only considered if the upper limit exceeds 750×109/L.
A Coulter counter is an apparatus for counting and sizing particles suspended in electrolytes. The Coulter counter is the commercial term for the technique known as resistive pulse sensing or electrical zone sensing. The apparatus is based on the Coulter principle named after its inventor, Wallace H. Coulter.
Clinical pathology is a medical specialty that is concerned with the diagnosis of disease based on the laboratory analysis of bodily fluids, such as blood, urine, and tissue homogenates or extracts using the tools of chemistry, microbiology, hematology, molecular pathology, and Immunohaematology. This specialty requires a medical residency.
Wallace H. Coulter was an American electrical engineer, inventor, and businessman. The best known of his 85 patents is the Coulter principle, which provides a method for counting and sizing microscopic particles suspended in fluid. His invention of the Coulter Counter made possible today's most common medical diagnostic test: the complete blood count (CBC). The Coulter principle is used in quality control of consumer products, such as chocolate and beer, paint and toners, and was even used to analyze Moon dust.
A medical laboratory or clinical laboratory is a laboratory where tests are conducted out on clinical specimens to obtain information about the health of a patient to aid in diagnosis, treatment, and prevention of disease. Clinical medical laboratories are an example of applied science, as opposed to research laboratories that focus on basic science, such as found in some academic institutions.
Cytometry is the measurement of number and characteristics of cells. Variables that can be measured by cytometric methods include cell size, cell count, cell morphology, cell cycle phase, DNA content, and the existence or absence of specific proteins on the cell surface or in the cytoplasm. Cytometry is used to characterize and count blood cells in common blood tests such as the complete blood count. In a similar fashion, cytometry is also used in cell biology research and in medical diagnostics to characterize cells in a wide range of applications associated with diseases such as cancer and AIDS.
In hematology, red cell agglutination or autoagglutination is a phenomenon in which red blood cells clump together, forming aggregates. It is caused by the surface of the red cells being coated with antibodies. This often occurs in cold agglutinin disease, a type of autoimmune hemolytic anemia in which people produce antibodies that bind to their red blood cells at cold temperatures and destroy them. People may develop cold agglutinins from lymphoproliferative disorders, from infection with Mycoplasma pneumoniae or Epstein–Barr virus, or idiopathically. Red cell agglutination can also occur in paroxysmal nocturnal hemoglobinuria and warm autoimmune hemolytic anemia. In cases of red cell agglutination, the direct antiglobulin test can be used to demonstrate the presence of antibodies bound to the red cells.
Cell counting is any of various methods for the counting or similar quantification of cells in the life sciences, including medical diagnosis and treatment. It is an important subset of cytometry, with applications in research and clinical practice. For example, the complete blood count can help a physician to determine why a patient feels unwell and what to do to help. Cell counts within liquid media are usually expressed as a number of cells per unit of volume, thus expressing a concentration.
Pseudothrombocytopenia (PTCP) or spurious thrombocytopenia is an in-vitro sampling problem which may mislead the diagnosis towards the more critical condition of thrombocytopenia. The phenomenon may occur when the anticoagulant used while testing the blood sample causes clumping of platelets which mimics a low platelet count. The phenomenon has first been reported in 1969.
Hematology analyzers are used to count and identify blood cells at high speed with accuracy. During the 1950s, laboratory technicians counted each individual blood cell underneath a microscope. Tedious and inconsistent, this was replaced with the first, very basic hematology analyzer, engineered by Wallace H. Coulter. The early hematology analyzers relied on Coulter's principle. However, they have evolved to encompass numerous techniques.
A white blood cell differential is a medical laboratory test that provides information about the types and amounts of white blood cells in a person's blood. The test, which is usually ordered as part of a complete blood count (CBC), measures the amounts of the five normal white blood cell types – neutrophils, lymphocytes, monocytes, eosinophils and basophils – as well as abnormal cell types if they are present. These results are reported as percentages and absolute values, and compared against reference ranges to determine whether the values are normal, low, or high. Changes in the amounts of white blood cells can aid in the diagnosis of many health conditions, including viral, bacterial, and parasitic infections and blood disorders such as leukemia.
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