Smart palm-size optofluidic hematology analyzer for automated imaging-based leukocyte concentration detection

A critical function of flow cytometry is to count the concentration of blood cells,which helps in the diagnosis of certain diseases.However,the bulky nature of commercial flow cytometers makes such tests only available in hospitals or laboratories,hindering the spread of point-of-care testing(POCT),especially in underdeveloped areas.Here,we propose a smart Palm-size Optofluidic Hematology Analyzer based on a miniature fluorescence microscope and a microfluidic platform to lighten the device to improve its portability.This gadget has a dimension of 35×30×80 mm and a mass of 39 g,less than 5%of the weight of commercially available flow cytometers.Additionally,automatic leukocyte concentration detection has been realized through the integration of image processing and leukocyte counting algorithms.We compared the leukocyte concentration measurement between our approach and a hemocytometer using the Passing-Bablok analysis and achieved a correlation coefficient of 0.979.Through Bland-Altman analysis,we obtained the relationship between their differences and mean measurement values and established 95%limits of agreement,ranging from−0.93×10^(3)to 0.94×10^(3)cells/μL.We anticipate that this device can be used widely for monitoring and treating diseases such as HIV and tumors beyond hospitals.

Development of the personalized criteria for microscopic review following four different series of hematology analyzer in a Chinese large scale hospital

Background A generally accepted guideline （＂41 rules＂） published by the International Consensus Group for Hematology Review （ICGHR） can not be suitable for all the laboratories because the facility type, laboratory requirements, sample volume, review rate, turn around time, instrument model and characters etc. are quite different from each other, which may cause a higher workload for microscopy review or lead to false or misleading results. Therefore, we decided to develop the personalized review criteria for 4 series of hematology analyzers in the same hospital, and describe all the implement procedures in detail. Methods The total 1770 blood samples were collected from Peking Union Medical College Hospital. Referring to the suggested criteria by international consensus group for hematology review （＂41 rules＂）, the personalized review criteria for 4 series of hematology analyzers including Siemens Advia 2120, Sysmex XE-2100, Sysmex XT-1800i and Sysmex XS-800i were established and validated by adjusting the rules in order to reduce the false positive rate and keep the false negative acceptable by clinical. Results Using the ＂41 rules＂, high review rates of 37.94%, 35.56%, 33.44% and 37.94% were got respectively in Siemens Advia 2120, Sysmex XE-2100, Sysmex XT-1800i and Sysmex XS-800i. Three false positive rules mainly were observed in all of 4 analyzers： white blood cell 〈3×10^9/L or 〉30×10^9/L, platelet 〈100×10^9/L or 〉1000×10^9/L and immature granulocyte. Specialized rules were observed in different series of analyzers, atypicaVvariant lymphs flag were found mainly in Sysmex XE-2100, Aniso-RBC were found mainly in Sysmex XT-1800i, flag of ＂immature granulocyte＂ mainly in Sysmex XS-800i, Micro-RBC, Macro-RBC and Aniso-RBC mainly in Siemens Advia 2120. Rules of immature granulocyte blast, and NRBC flag would be mainly triggered by hematology malignant tumor. We could not delete these rules due to the risk of false negative of serious disease, other rules were deleted or revised. After continually optimizing to the rules, we finalized the criteria suitable for Siemens Advia 2120, Sysmex XE-2100, Sysmex XT-1800i and Sysmex XS-800i in our laboratory. The false negative rates were 2.94%, 2.86%, 3.10% and 2.78%, the review rates were 31.07%, 30.00%, 30.01% and 30.09%, and there was no hematology malignant tumor missed. Validated by 547 samples, the false negative rates of our optimized rules were 0.37%, 0.55%, 0.55%, and 0.91% respectively. Conclusion The criteria can be based on the criteria established by International Consensus Group for Hematology Review but must be optimized according to the different requirements.

Evaluation of Atypical Lymphocyte Warnings of Sysmex XE-4000 in Outpatient Children

This study aimed to evaluate the atypical lymphocyte warnings of Sysmex XE-4000 in outpatient children. [Method] Randomly 280 specimens of outpatient children were selected to analyze atypical lymphocytes with Sysmex XE-4000 and artificial smear microscopy simultaneously. [Result] With artificial smear microscopy as the gold standard, the atypical lymphocyte warnings of Sysmex XE-4000 in outpatient children exhibited a sensitivity of 97.4%, specificity of 69.3%, positive predictive value （PPV） of 55%, and negative predictive value （NPV） of 98.5%. [Conclusion] Sysmex XE-4000 shows a high sensitivity in atypical lymphocyte warnings, which can reduce the number of blood smears, improve the specificity of microscopy, and decline the labor intensity of inspection personnel. However, there are stil certain false positives to be confirmed by artificial microscopy.

The exploration of cell population data in clinical use: Beyond infectious diseases

Cell population data(CPD)is regarded as the fingerprint of a blood cell at a given moment.CPD parameters harbor information associated with cell morphology and can be automatically generated using modern hematological analyzers.Various studies have revealed many unique clinical applications for CPD,especially for infectious diseases,such as sepsis.For example,one monocyte-related CPD parameter is the monocyte distribution width(MDW),which can be generated using a Beckman Coulter hematological analyzer.MDW has received FDA and CE approval for aiding in sepsis diagnosis in adult patients in the emergency department.Additionally,MDW can serve as a diagnostic biomarker in patients infected with SARS-CoV-2.CPD has also been widely explored for possible clinical applications beyond infectious dis-eases,such as for predicting myelodysplastic syndromes,screening for he-matological malignancies,and detecting sterile inflammation.CPD parameter measurements are easily obtained and quite cost-effective,making them practical for clinical use.However,there are some potential drawbacks of CPD parameters.Some pre-analytical conditions can affect CPD values.Further-more,CPD are specific to certain hematological analyzers and the result cannot be transferred between different analyzers.The practical usefulness of CPD reference intervals is also still questionable.In this review,wesummarize the current studies related to CPD and its clinical applications.Additional well-designed clinical studies related to CPD are still expected.

Clinical utility of automated platelet clump count in the screening for ethylene diamine tetraacetic acid-dependent pseudothrombocytopenia

Background Platelet （PLT） clumping occurring in pseudothrombocytopenia （PTCP） can result in inaccurate PLT. Automated platelet clump count （APCC） is a quantitative parameter of platelet aggregation. In this study, we evaluated the clinical utility of APCC in the screening for platelet aggregation related ethylene diamine tetraacetic acid （EDTA）-dependent PTCP （EDTA-PTCP）. Methods A total of 105 patients and 200 healthy individuals were enrolled in this study. Blood samples were collected with dipotassium EDTA and sodium citrate respectively. ADVIA 2120 hematology analyzer was used to perform complete blood count （CBC） and APCC. Blood smears of both EDTA- and citrate-anticoagulated samples were made for microscope observation and manual PLT counting. Results In 25 patients with EDTA-PTCP patients, for EDTA-2K anticoagulated-blood, PLT was （55±6）×10^9/L, significantly lower than citrate anticoagulated blood （（186±13）×10^9/L））. APCC was （905±694）×10^9/L, significantly higher than citrate anticoagulated blood （98±37）×10^9/L. In true thrombocytopenia and healthy control groups, APCC was （63±60）×10^9/L and （69±59）×10^9/L respectively and there was no significant difference between EDTA and citrate anticoagulants. Receiver operator characteristic （ROC） curve showed both sensitivity and specificity of APCC were 96% when the cutoff value of APCC was set as 182×10^9/L. Other platelet parameters had poor performance. Conclusion The APCC has a good sensitivity and specificity in differentiating EDTA-PTCP from true thrombocytopenia compared with other platelet parameters.