Interference of bovine hemoglobin-based oxygen carrier-201 (Hemopure) on four hematology analyzers

Introduction: Hemoglobin-based oxygen carriers, for example HBOC-201 (Hemopure), are aimed to bridge acute anemia when blood transfusion is not available or refused by the patient. However, since HBOC-201 appears free in plasma, it interferes with laboratory tests. This study presents an overview of HBOC-201 interference on four commonly used hematology analyzers and suggests treatment monitoring possibilities. Methods: Blood samples were spiked with therapeutic doses of HBOC-201 and nine hematology parameters were measured with the Sysmex XN-20, Siemens Advia 2120i, Abbott Alinity Hq and Abbot Cell Dyn Sapphire hematology analyzers. The results were compared to control samples and the bias was determined. Results: Most parameters, including all cell counts, hematocrit and MCV, showed a non-significant bias compared to control. However, the standard, total hemoglobin (Hb) measurement as well as MCH and MCHC showed poor agreement with control, as HBOC-201 was included in this measurement. Yet, the flow cytometry-based Hb method quantified intracellular Hb in spiked samples, excluding HBOC-201. Conclusion: Of all included hematology parameters, only total Hb and the associated MCH and MCHC suffered from interference. In contrast, the flow cytometry-based Hb measurement provided an accurate measure of intracellular Hb. The difference between total Hb and cellular Hb represents the HBOC-201 concentration and can be used to monitor HBOC-201 treatment.</p

Interference of bovine hemoglobin-based oxygen carrier-201 (Hemopure) on four hematology analyzers

Introduction: Hemoglobin-based oxygen carriers, for example HBOC-201 (Hemopure), are aimed to bridge acute anemia when blood transfusion is not available or refused by the patient. However, since HBOC-201 appears free in plasma, it interferes with laboratory tests. This study presents an overview of HBOC-201 interference on four commonly used hematology analyzers and suggests treatment monitoring possibilities. Methods: Blood samples were spiked with therapeutic doses of HBOC-201 and nine hematology parameters were measured with the Sysmex XN-20, Siemens Advia 2120i, Abbott Alinity Hq and Abbot Cell Dyn Sapphire hematology analyzers. The results were compared to control samples and the bias was determined. Results: Most parameters, including all cell counts, hematocrit and MCV, showed a non-significant bias compared to control. However, the standard, total hemoglobin (Hb) measurement as well as MCH and MCHC showed poor agreement with control, as HBOC-201 was included in this measurement. Yet, the flow cytometry-based Hb method quantified intracellular Hb in spiked samples, excluding HBOC-201. Conclusion: Of all included hematology parameters, only total Hb and the associated MCH and MCHC suffered from interference. In contrast, the flow cytometry-based Hb measurement provided an accurate measure of intracellular Hb. The difference between total Hb and cellular Hb represents the HBOC-201 concentration and can be used to monitor HBOC-201 treatment

Microfluidic organ-on-chip technology for blood-brain barrier research

Organs-on-chips are a new class of microengineered laboratory models that combine several of the advantages of current in vivo and in vitro models. In this review, we summarize the advances that have been made in the development of organ-on-chip models of the blood-brain barrier (BBBs-on-chips) and the challenges that are still ahead. The BBB is formed by specialized e3ndothelial cells and separates blood from brain tissue. It protects the brain from harmful compounds from the blood and provides homeostasis for optimal neuronal function. Studying BBB function and dysfunction is important for drug development and biomedical research. Microfluidic BBBs-on-chips enable real-time study of (human) cells in an engineered physiological microenvironment, for example incorporating small geometries and fluid flow as well as sensors. Examples of BBBs-on-chips in literature already show the potential of more realistic microenvironments and the study of organ-level functions. A key challenge in the field of BBB-on-chip development is the current lack of standardized quantification of parameters such as barrier permeability and shear stress. This limits the potential for direct comparison of the performance of different BBB-on-chip models to each other and existing models. We give recommendations for further standardization in model characterization and conclude that the rapidly emerging field of BBB-on-chip models holds great promise for further studies in BBB biology and drug development

Barriers-on-chips: Measurement of barrier function of tissues in organs-on-chips

Disruption of tissue barriers formed by cells is an integral part of the pathophysiology of many diseases. Therefore, a thorough understanding of tissue barrier function is essential when studying the causes and mechanisms of disease as well as when developing novel treatments. In vitro methods play an integral role in understanding tissue barrier function, and several techniques have been developed in order to evaluate barrier integrity of cultured cell layers, from microscopy imaging of cell-cell adhesion proteins to measuring ionic currents, to flux of water or transport of molecules across cellular barriers. Unfortunately, many of the current in vitro methods suffer from not fully recapitulating the microenvironment of tissues and organs. Recently, organ-on-chip devices have emerged to overcome this challenge. Organs-on-chips are microfluidic cell culture devices with continuously perfused microchannels inhabited by living cells. Freedom of changing the design of device architecture offers the opportunity of recapitulating the in vivo physiological environment while measuring barrier function. Assessment of barriers in organs-on-chips can be challenging as they may require dedicated setups and have smaller volumes that are more sensitive to environmental conditions. But they do provide the option of continuous, non-invasive sensing of barrier quality, which enables better investigation of important aspects of pathophysiology, biological processes, and development of therapies that target barrier tissues. Here, we discuss several techniques to assess barrier function of tissues in organs-on-chips, highlighting advantages and technical challenges