Hematology analyzer
A hematology analyzer is an automated instrument that counts and sorts the cells of a blood sample. It reports the numbers of red cells, white cells and platelets, the hemoglobin and the sizes of the red cells, which together are the complete blood count, and most models also divide the white cells into neutrophils, lymphocytes, monocytes, eosinophils and basophils. Many add reticulocytes, the young red cells, and nucleated red cells, which are not normally found in the blood of adults. The cells are measured one at a time by electrical impedance, by the scattering of light, by fluorescence or by a cytochemical stain, and the makers combine the methods in different ways. Before the machines, a technician counted cells under a microscope in a ruled chamber, a task that took 15 to 30 minutes.[1]
Methods
Impedance counting is the Coulter principle. Cells in a conductive diluent pass through a small aperture between two electrodes, each cell acts as an insulator and raises the resistance of the path for an instant, the number of pulses is the count and the height of a pulse is proportional to the volume of the cell. To turn a count into a concentration the instrument must know how much suspension crossed the aperture, so the vacuum that draws it through is held at a regulated volume. White cells are counted after a lytic reagent has destroyed the red cells and left the nuclei of the white cells intact, and the same lysed sample gives the hemoglobin by the absorbance of a pigment at 525 nm.[2]
Optical counting sends cells in single file through a laser beam. A sheath of cell-free liquid keeps them in line, a technique introduced by Crosland-Taylor in 1953, and detectors read the light scattered at several angles and, in some channels, the fluorescence of a dye that binds nucleic acids.[3] Red cells are biconcave discs whose scatter depends on their shape and on the refractive index that their hemoglobin gives them, which makes size hard to read by light.[3] One maker spheres the red cells with a reagent before they reach the beam. The principles that four makers state in filings with the U.S. Food and Drug Administration are these.
| Instrument | Red cells and platelets | Hemoglobin | White-cell differential |
|---|---|---|---|
| Sysmex XN-Series[4] | Sheath flow, direct-current detection (impedance) | SLS-hemoglobin method | Flow cytometry with a semiconductor laser: forward scatter, side scatter and side fluorescence |
| Beckman Coulter DxH 900[2] | Coulter principle | Photometry at 525 nm after lysis | VCSn: volume, conductivity, several angles of scatter and axial light loss, with a diode laser |
| Abbott Alinity hq[5] | Optical and fluorescence flow cytometry with hydrodynamic focusing, by multi-angle polarized scatter separation | Absorption spectrophotometry | The same flow cytometry |
| Siemens ADVIA 2120 and 2120i[6] | One optical cytometer after dilution, with the red cells sphered, and size from two scatter angles | Cyanide-free or cyanide-containing method | Peroxidase stain, and a basophil and lobularity channel read by two-angle laser scatter |
Impedance counts the red cells and platelets in two of the four, and light counts them in the other two. Molecular Reality's founder writes in his introduction to Epic Quest Bio that almost all instruments for the complete blood count "are still, essentially, Coulter Counters"; the statement holds for the aperture instruments and not for the others.[7] Sysmex describes the differential of its instruments as one in which cells "are differentiated in the flow cell according to their fluorescence signal, size and internal structure", and the chamber is described under Flow cell.[8] The Abbott filing adds reticulocyte and nucleated red cell counts to the list of quantities that the Alinity measures by flow cytometry.[5]
History
The first instruments were Coulter counters. The Model S of late 1968 printed seven parameters from one sample in under a minute.[9] The Hemalog-D of Technicon, introduced in 1974, combined light scatter with absorbance to produce a complete differential count, and in 1986 the VCS transducer of Beckman Coulter measured volume, conductivity and scatter.[3]
Checking the analyzers
An analyzer flags samples that it cannot classify, and a technician then looks at a smear. The International Council for Standardization in Haematology publishes guidelines for evaluating analyzers, including their differential and reticulocyte counts.[10] A comparison of five analyzers from four makers on 349 patient samples found good agreement on the basic counts and less on reticulocytes, nucleated red cells and differentials.[11] Between control runs a laboratory can also watch its patients. In 1974 Bull and colleagues studied estimators for quality-control procedures derived from the red-cell indices of patient samples.[12]
Because the machines keep a measurement for every cell, new parameters can be computed from the same pulses. Monocyte distribution width, a measure of the spread of monocyte size reported by Beckman Coulter instruments, was tested in 2,158 adults in three emergency departments in 2017 and 2018. By the Sepsis-2 criteria a value above 20.0 units separated sepsis from the other conditions with an area under the curve of 0.79.[13]
At Molecular Reality
The company's own first blood through a pore came in late 2018, when its founder "grabbed a razor blade and bled into the flow cell", in the episode it calls the rain of blood.[14] The company's pores measure by the principle that Wallace H. Coulter patented in 1953.
See also
References
- ^ M. D. Graham (November 18, 2020). "The Coulter Principle: For the Good of Humankind". University of Kentucky. Retrieved October 25, 2026.
- ^ a b "510(k) substantial equivalence determination decision summary K240252: UniCel DxH 900 Coulter cellular analysis system". U.S. Food and Drug Administration. Retrieved October 25, 2026.
- ^ a b c Daves, M.; et al. (2024). "Modern hematology analyzers: beyond the simple blood cells count (with focus on the red blood cells)". Journal of Laboratory and Precision Medicine 9: 4. doi:10.21037/jlpm-23-32.
- ^ "510(k) substantial equivalence determination decision summary K141681: Sysmex XN-Series (XN-11, XN-21)". U.S. Food and Drug Administration. Retrieved October 25, 2026.
- ^ a b "510(k) substantial equivalence determination decision summary K220031: Alinity h-series system". U.S. Food and Drug Administration. Retrieved October 25, 2026.
- ^ "510(k) substantial equivalence determination decision memorandum K162977: ADVIA 2120/2120i". U.S. Food and Drug Administration. Retrieved October 25, 2026.
- ^ Kemmishtree (March 2026). "Epic Quest Bio". Molecular Reality Corporation.
- ^ "Automated differential application". Sysmex. Retrieved October 25, 2026.
- ^ M. D. Graham (November 18, 2020). "The Coulter Principle: For the Good of Humankind, chapter 8, "Elaboration"". University of Kentucky. Retrieved October 25, 2026.
- ^ Briggs, C.; et al. (2014). "ICSH guidelines for the evaluation of blood cell analysers including those used for differential leucocyte and reticulocyte counting". International Journal of Laboratory Hematology 36 (6): 613-627. doi:10.1111/ijlh.12201.
- ^ Bruegel, M.; et al. (2015). "Comparison of five automated hematology analyzers in a university hospital setting: Abbott Cell-Dyn Sapphire, Beckman Coulter DxH 800, Siemens Advia 2120i, Sysmex XE-5000 and XN-2000". Clinical Chemistry and Laboratory Medicine 53 (7): 1057-1071. doi:10.1515/cclm-2014-0945.
- ^ Bull, B. S.; et al. (1974). "A study of various estimators for the derivation of quality control procedures from patient erythrocyte indices". American Journal of Clinical Pathology 61 (4): 473-481. doi:10.1093/ajcp/61.4.473.
- ^ Crouser, E. D.; et al. (2019). "Monocyte distribution width: a novel indicator of sepsis-2 and sepsis-3 in high-risk emergency department patients". Critical Care Medicine 47 (8): 1018-1025. doi:10.1097/CCM.0000000000003799.
- ^ Kemmishtree (March 29, 2026). "rain of blood". EQBio-OS.