METHOD FOR PREPARING A BLOOD SAMPLE FOR HEMATOLOGY

The present disclosure relates generally to improvements of hematology analysis, such as for patient care.

BACKGROUND

Hematology is a branch of medicine covering diseases related to the blood and its components, including methods of treatment, diagnosis, analysis, etc. Hematology encompasses a number of different assessments that can be performed on blood and/or components of the blood. One or more of the assessments could require preparation of a blood sample prior to the actual assessment.

Typical hematology analysis is performed in a laboratory setting, and requires transportation of a blood sample to the laboratory. Thus, there is significant time delay between receiving a blood sample and providing analysis, which can slow down necessary patient care.

SUMMARY

Accordingly, there is a need for accurate and fast hematology analysis in order to quickly assess and analyze components of a patient’s blood. In particular, there is a need for accurate and fast point-of-care hematology analysis.

Disclosed herein is a method of preparation of a blood sample with a reagent for hematology, the method comprising obtaining a first blood parameter of a first blood component of the blood sample, determining a preparation scheme based on the first blood parameter, and preparing the blood sample with a reagent according to the preparation scheme.

Further disclosed herein is a system for adaptive preparation of a blood sample for point of care hematology, the system including a controller, a reservoir for accommodating a reagent, and a cell measurement component for accommodating a blood sample, wherein the system is configured to perform any one of the methods disclosed herein.

It is an important advantage of the present disclosure to be able to provide properly prepared blood samples prior to a full analysis for determining certain hematological parameters. This can avoid failed testing due to improperly prepared blood samples, which can significantly delay results and thus patient care. Accordingly, it is an important advantage to provide accurate final hematological results based on a blood sample. Further, it is an important advantage to provide point-of-care hematological results, rather than having to transport the blood to a laboratory setting. Moreover, it is an important advantage of the present disclosure to be able to reduce changing consumables.

The present disclosure allows for improved preparation of blood samples for hematological analysis, in particular through the use of adjustable proper dosing of the blood sample with reagent. This can further improve the final results of the analysis, such as providing an accurate complete blood cell count. Further, advantageously the preparation, and eventual analysis, can all be done at a point-of-care facility, such as an emergency room. Additionally, the present disclosure allows for low mixing ratios of blood to reagent as compared to traditional ratios of about 1 : 10000 to 1 :50000. Thus, the disclosure can reduce the consumption of reagent per analysis, and accordingly a larger number of tests may be attained without having to increase the of reagent available to the analyzer, this further may reduce the need for changing consumables, enabling a smaller footprint.

BRIEF DESCRIPTION OF THE DRAWINGS

The above and other features and advantages of the present disclosure will become readily apparent to those skilled in the art by the following detailed description of example embodiments thereof with reference to the attached drawings, in which:

Fig. 1 illustrates a method as disclosed herein,

Fig. 2 illustrates a process as disclosed herein,

Figs. 3A-3B illustrate a schematic of a system utilizing methods disclosed herein, and

Fig. 4 illustrates a schematic of a system utilizing methods disclosed herein.

DETAILED DESCRIPTION

Various example embodiments and details are described hereinafter, with reference to the figures when relevant. It should be noted that the figures may or may not be drawn to scale and that elements of similar structures or functions are represented by like reference numerals throughout the figures. It should also be noted that the figures are only intended to facilitate the description of the embodiments. They are not intended as an exhaustive description of the invention or as a limitation on the scope of the invention. In addition, an illustrated embodiment needs not have all the aspects or advantages shown. An aspect or an advantage described in conjunction with a particular embodiment is not necessarily limited to that embodiment and can be practiced in any other embodiments even if not so illustrated, or if not so explicitly described.

A method of preparing a blood sample is disclosed. The method can be used to prepare a blood sample for hematology, e.g., blood analysis, blood component analysis, hematology analysis, hematological analysis, hematological assessment. In particular, the method can be used to prepare a blood sample for white blood cell differential, or white blood cell count, (WBC DIFF), e.g. including 3-part or 5-part white blood cell differential, or white blood cell count, (WBC DIFF). In particular, the method can be used to prepare a blood sample for complete-blood-counting (CBC), e.g. including 3-part or 5-part CBC. As discussed herein, CBC may include a 3-part or 5-part WBC DIFF, or the terms may be used interchangeably. Other components of CBC analysis may be used as well, such as for the measurement, e.g. counting, of platelets. The blood sample can be from a patient. The blood sample can be from a human or animal.

In one or more example methods, the blood sample is prepared prior to hematology analysis. For example, reagent may be added into the blood sample and/or the blood sample may be added into the reagent. As discussed, the reagent may lyse and/or stain components of the blood sample. Further, mixing could be performed to the blood sample. Also, incubation could be performed on the blood sample. In one or more example methods, pH of the blood sample can be adjusted. Other preparations could be performed as well, and the disclosure should not be so limited. Certain preparations are discussed as examples in more detail below.

Typically, preparations are designed for “standard” (e.g., normal) blood samples having particular properties (e.g., lipid/blood cell/platelet concentration, pH). However, more often than not the blood sample may not fit within the “standard” properties for one or more reasons, for instance, due to hereditary or environmental conditions. For example, the blood sample may have higher or lower red blood cell count outside of the “standard”, higher or lower cholesterol or other lipid content outside of the “standard”, among other parameters.

Accordingly, it may be advantageous to adjust the preparation of the blood sample prior to any hematology in order to properly prepare the non-standard blood sample to achieve accurate hematology assessment (e.g., vary a preparation scheme). If the standard preparation was used for a non-standard blood sample, accurate hematology assessment may not be achieved. Thus, additional adjustments may not need to be made, greatly speeding up the process. Further, by properly preparing the blood sample early in the process, the number of wasted samples may be reduced, along with the reduction of preparations needed during the procedure.

For example, the hematology can analyze one or more parameters of the blood sample. In one or more example methods, the method of preparing a blood sample can be used for a complete blood count (CBC) analysis. In one or more example methods, the method of preparing a blood sample can be used for a basic metabolic panel (BMP) analysis.

Advantageously, the disclosed methods can be used for point-of-care hematology testing (e.g., at the time and place of patient care). Thus, the method can be performed quickly and easily, such as in a patient’s room or in an emergency room. In one or more example methods, a blood sample can be taken directly from the patient to a system within the same room. For example, the method can be performed in a diagnostic room and/or testing room and/or hospital room and/or surgery room and/or operating room. Accordingly, blood sample can be taken from a patient and tested in the same area without transporting the blood sample. This can advantageously lead to the avoidance of transportation mix-ups or damage to the blood sample. Further, the methods can provide for significantly faster hematological analysis and results, thereby leading to improved patient care. Thus, the blood sample need not be taken to a laboratory, and the preparation and analysis can be performed in a single room, such as with the patient in it.

Alternatively or additionally, the disclosed methods may be used outside of point-of care hematology testing, such as laboratory hematology testing. Thus, the blood sample may be sent away from the patient.

Generally, one or more example methods of the disclosure can be configured to properly prepare, e.g., treat, modify, pretreat, a blood sample for hematological testing (e.g., analysis, assessment). The blood sample may be taken directly from a patient. The blood sample may be from a storage. The blood sample may be an aspirated blood sample. The blood sample discussed herein may be understood as an aspirated blood sample.

Different preparation schemes can be used based on ascertained blood parameter(s) of the blood sample. In one or more example methods, the preparation scheme can vary based on red blood cell count of the blood sample. In one or more example methods, the preparation scheme can vary based on cholesterol content/count of the blood sample. In one or more example methods, the preparation scheme can vary based on white blood cell count. In one or more example methods, the preparation scheme can vary based on lipid content/count of the blood sample. In one or more example methods, the preparation scheme can vary based on platelet count of the blood sample. In one or more example methods, the preparation scheme can vary based on pH. In one or more example methods, the preparation scheme can vary based on an electrical property, such as impedance (resistance and/or capacitance/inductance) and/or conductivity, e.g. at one or more frequencies, of the blood sample. In one or more example methods, the preparation scheme can vary based on an optical property, such as absorbance and/or transmittance, e.g., at one or more wavelengths, of the blood sample. In one or more example methods, the preparation scheme can vary based on refractive index or a change in refractive index of a plasma phase of the blood sample. The refractive index or change in refractive index could be indicative of lipids and/or lipid content.

In one or more example methods, the hematological analysis may be a complete blood cell count. Of course, other analysis may be performed on the blood sample, and this is only one example. In one or more example methods, the complete blood cell count may be performed via an image capture device, e.g., image capturer, image capturing software. Accordingly, it can be advantageous to lyse, e.g., remove, destroy, eliminate, red blood cells. Further, it can be advantageous to stain, e.g., dye, make optically visible, white blood cells and/or platelets. Thus, the white blood cells and/or platelets can be counted from the complete blood cell count hematological analysis. Accordingly, one or more example methods can prepare a blood sample by staining and/or lysing the blood sample based on parameter(s), such as the first blood parameter, of the blood sample. The preparing can be adjusted via different preparation schemes based on the parameter(s) including the first blood parameter of the blood sample.

For example, if a blood sample has an increased or decreased amount of red blood cells over a “standard” amount of red blood cells, it may be advantageous to add more of a lysing reagent to the blood sample to remove the red blood cells. Low concentration of red blood cells can dilute the reagent and reduce lysing activity, and high concentration of red blood cells can require more and/or less reagent to lyse. This can be determined before any hematological analysis is performed, which can greatly speed up the process and eliminate faulty blood samples. By properly preparing the blood sample prior to any hematological analysis, a faster and more accurate analysis can be performed.

As another example, if a blood sample has an increased amount of lipids and/or cholesterol over a “standard” amount of lipids and/or cholesterol, it may be advantageous to add more of a lysing reagent to the blood sample to remove the red blood cells. This can be determined before any hematological analysis is performed, which can greatly speed up the process and eliminate faulty blood samples. By properly preparing the blood sample prior to any hematological analysis, a faster and more accurate analysis can be performed.

The preparation can occur in a device (e.g., module, machine, housing, system, module, analyzer) separate from the hematological analysis device (e.g., module, machine, housing, system, module, analyzer). For example, the preparing device may be physically separate from the hematological analysis device (e.g., physical separated, not physically connected, close by). Alternatively, the preparation can occur in a device (e.g., module, machine, housing, system, module, analyzer) combined or integrated with the hematological analysis device (e.g., module, machine, housing, system, module, analyzer).

In one or more example methods, the method is performed by a blood analyzer or hematological analysis device. Thus, once a blood sample is inserted into the device, the preparation and hematological analysis can all occur without any user touching the blood sample again. Alternatively, a user can move the prepared blood sample to the hematological analysis device. In this instance, the preparation device can be separate, e.g., may not be in fluid communication, from the hematological analysis device.

In one or more example methods, a blood sample (e.g., blood) can be received (e.g., obtained, provided). The blood sample can be from a patient. For example, a blood sample can be withdrawn from a patient. Alternatively, the blood sample may already have been withdrawn from the patient prior to the hematology. The patient may be directly connected to the device.

The blood sample, such as the aspirated blood sample, may be 5, 10, 15, 20, 25, 30, 35, 40, 45, or 50mL. The blood sample, such as the aspirated blood sample, may be greater than 5, 10, 15, 20, 25, 30, 35, 40, 45, or 50mL. The blood sample, such as the aspirated blood sample, may be less than 5, 10, 15, 20, 25, 30, 35, 40, 45, or 50mL.

The blood sample, such as the aspirated blood sample, may be 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, or 70 pL. The blood sample, such as the aspirated blood sample, may be greater than 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, or 70 pL. The blood sample, such as the aspirated blood sample, may be less than 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, or 70 pL. The blood sample, such as the aspirated blood sample, may be between 10 pL and 120pL. In one or more example methods, the blood sample may be mixed (e.g., pretreated) with an anticoagulant, e.g., blood thinner. The anticoagulant may include, but is not limited to EDTA, coumarins, heparins, synthetic pentasaccharides, citrate, lloprost, MgSO4 tubes, and their derivatives/alternatives and combinations. The anticoagulant may be added into the blood sample prior to any hematological testing. In one or more example methods, the anticoagulant can be in a container receiving the blood sample from the patient. In alternative methods, the blood sample is not mixed with an anticoagulant. The inclusion of the anticoagulant can be part of the preparation. The anticoagulant may be part of the blood sample itself.

The blood sample with anticoagulant, such as the aspirated blood sample with anticoagulant, may be 5, 10, 15, 20, 25, 30, 35, 40, 45, or 50mL. The blood sample with anticoagulant, such as the aspirated blood sample with anticoagulant, may be greater than 5, 10, 15, 20, 25, 30, 35, 40, 45, or 50mL. The blood sample with anticoagulant, such as the aspirated blood sample with anticoagulant, may be less than 5, 10, 15, 20, 25, 30, 35, 40, 45, or 50mL.

The blood sample with anticoagulant, such as the aspirated blood sample with anticoagulant, may be 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, or 70 pL. The blood sample with anticoagulant, such as the aspirated blood sample with anticoagulant, may be greater than 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, or 70 pL. The blood sample with anticoagulant, such as the aspirated blood sample with anticoagulant, may be less than 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, or 70 pL. The blood sample, such as the aspirated blood sample, may be between 10 pL and 120pL.

In one or more example methods, saline can be added into the blood sample. This can dilute the sample. The dilution may be taken in consideration for one or more of the methods detailed below. In alternative embodiments, no saline is added to the blood sample. Thus, the blood sample may not be diluted with saline.

The blood sample can be received in a container. The container could be a tube. The container could be a capillary tube. The container could be a cylinder. The container could be a vacuum tube. The container could be a cuvette. The container can be a syringe. The container can be sized and configured to fit within an inlet (e.g., inlet module, opening, aperture, gap, slot, receiver) in a system (e.g., housing, system, machine, tester, multicomponent system) for providing hematological analysis on the blood sample. The container may provide a fluid connection between a blood sample and the inlet. The container can be a multi-use container. The inlet may be in a housing or other system. Thus, the blood sample can be received by the device and/or system to perform one or more example methods. Once the blood sample is received, it may follow one or more fluid pathways. These fluid pathways can be, for example, tubes, pipes, capillaries, conduits, hoses, ducts, etc. The method steps discussed herein may all occur on the fluid pathway.

In one or more example methods, the fluid pathway may end at a waste module. The blood sample may be disposed in the waste module.

Once received by the system, the method can be a method of preparation of a blood sample with a reagent for hematology.

In one or more example methods, the method can include obtaining a first blood parameter. The first blood parameter can be obtained from the blood sample. Specifically, the first blood parameter can be obtained from a first blood component of the blood sample. Thus, in one or more example methods, the first blood parameter can be obtained from a first blood component, and not from the blood sample as a whole. For example, this may not include a volume of the blood sample. Though in alternate embodiments this may include the volume of the blood sample.

The first blood parameter may be any number of parameters of the first blood component. In one or more example methods, the first blood parameter may be a red blood cell content. In one or more example methods, the first blood parameter may be a plasma content. In one or more example methods, the first blood parameter may be a lipid content. For example, the lipid content may be from a sample quality index, such as a HIL index. In one or more example methods, the first blood parameter may be a white blood cell content. In one or more example methods, the first blood parameter may be a blood gas content. In one or more example methods, the first blood parameter may be a platelet content. In one or more example methods, the first blood parameter may be a protein content. In one or more example methods, the first blood parameter may be a cholesterol content. In one or more example methods, the first blood parameter may be total cholesterol content. In one or more example methods, the first blood parameter may be LDL content. In one or more example methods, the first blood parameter may be HDL content. In one or more example methods, the first blood parameter may be a ratio between LDL and HDL. In one or more example methods, the first blood parameter may be triglyceride content. In one or more example methods, the first blood parameter may be a hematocrit content. The first blood parameter may be more than one of the parameters discussed herein (e.g., a combination of two or more). Other first blood parameters can be used as well, and the particular blood parameter is not limiting. In one or more example methods, the first blood parameter can be obtained during aspiration of the blood sample. The first blood parameter can be obtained after aspiration of the blood sample.

In one or more example methods, the first blood parameter may be a red blood cell content indicative of certain contents of the first blood component. For example, the red blood cell content may be indicative of a plasma content of the blood sample. The red blood cell content may be indicative of a lipid content of the blood sample. In one or more example methods, the first blood parameter may be a glucose content. In one or more example methods, the first blood parameter may be an electrolyte content. The red blood cell content may be indicative of both a lipid content and a plasma content of the blood sample.

The obtaining may be performed via a number of different methods. In one or more example methods, the obtaining the first blood parameter of the first blood component of the blood sample comprises obtaining image data of the blood sample. In one or more example methods, the obtaining the first blood parameter of the first blood component of the blood sample comprises obtaining sensor data of the blood sample. In one or more example methods, the obtaining the first blood parameter of the first blood component of the blood sample comprises obtaining image data and/or sensor data of the blood sample.

In one or more example methods, the first blood parameter may be obtained directly. In one or more example methods, the first blood parameter may be obtained indirectly. For example, a sum of electrolytes and similar analytes of the osmolality may be measured, which can affect the ability to lyse and stain cells.

The first blood parameter can be determined from the image data. The first blood parameter can be determined from the sensor data. The sensor data may be or comprise optical sensor data from one or more optical sensors. The first blood parameter can be determined from the image data and/or the sensor data, such as optical sensor data.

Obtaining the image data may be performed via taking photographs, e.g. images. For example, the images can be taken from one or more cameras. Alternatively, other imaging systems (e.g., image capturing systems, image capturer) can perform the obtaining the image data. The image capturing system may be associated with a fluid pathway of the blood sample. The image capturing system may output data indicative of the first blood parameter.

Obtaining the sensor data may be performed via one or more sensors, e.g., detectors, electronics. The sensor(s) may be along the fluid pathway in order to obtain the sensor data while the blood sample passes through the system. The sensors may output data indicative of the first blood parameter.

In one or more example methods, the sensor may be an absorbance sensor and/or a transmittance sensor and/or a refractive index sensor and/or a liquid sensor and/or a hematocrit sensor. In one or more example methods, the sensor may be an optical sensor.

As mentioned, the sensor may be an impedance sensor. The impedance sensor may provide sensor data, which may be indicative of the first blood parameter. The impedance sensor may provide a first blood parameter indicative of electrolyte content. The impedance sensor may provide a first blood parameter indicative of lipid content. The impedance sensor may provide a first blood parameter indicative of hematocrit content. The impedance sensor may provide a first blood parameter indicative of electrolyte content and/or lipid content and/or hematocrit content.

In one or more example methods, the obtaining the first blood parameter comprises performing a blood gas (BG) analysis. In one or more example methods, the obtaining the first blood parameter comprises performing a basic metabolic panel (BMP) analysis. In one or more example methods, the obtaining the first blood parameter comprises performing the BG analysis and/or the BMP analysis. A BG analyzer and/or BMP analyzer may be used, and they may be in fluid communication with the blood sample with or without the reagent. The BG analyzer and/or the BMP analyzer may be on a separate fluid pathway, and thus the blood sample with or without the reagent may be divided to the BG analyzer and/or the BMP analyzer, while the remainder continues through the discussed path.

Further, the determining the first blood parameter can be based on the blood gas (BG) analysis. The determining the first blood parameter can be based on the basic metabolic panel (BMP) analysis. The determining the first blood parameter can be based on the blood gas (BG) and/or the basic metabolic panel (BMP) analysis. The blood gas analysis may include one or more of blood gas, e.g., pH, pCO?, pO?, electrolytes, metabolites, and oximetry (CO-OX).

In one or more example methods, the obtaining the first blood parameter comprises hemolysis detection. The hemolysis detection can be sensitive to refraction index changes from lipids.

In one or more example methods, the obtaining the first blood parameter comprises sensing one or more electrical and/or optical properties of the blood sample. In other words, the first blood parameter, and optionally further blood parameters may be indicative of an electrical and/or optical property of the blood sample.

In one or more example methods, the obtaining the first blood parameter comprises performing a conductivity analysis of the blood sample. In one or more example methods, the obtaining the first blood parameter comprises performing a conductivity analysis. The conductivity analysis can determine the hematocrit of a blood sample (e.g., the volume percentage of red blood cells). For example, electrodes can be used to measure the conductivity. Osmolality can be measured/determined/estimated from the conductivity. The electrodes can span the fluid pathway in order to obtain sensor data of the blood sample. The electrodes can be incorporated into the fluid pathway.

In one or more example methods, the obtaining the first blood parameter comprises performing a light intensity analysis of the blood sample. In one or more example methods, the obtaining the first blood parameter comprises performing a light intensity analysis, e.g., at one or more different wavelengths. For example, an optical sensor can be used. The optical sensor and/or light source can be at 509, 522, 549, 569, 587, 650, 660, 670, 680, or 690nm.

In one or more example methods, the obtaining the first blood parameter comprises performing a viscosity analysis of the blood sample. In one or more example methods, the obtaining the first blood parameter comprises performing a viscosity analysis.

In one or more example methods, the obtaining the first blood parameter comprises performing a pH analysis of the blood sample. In one or more example methods, the obtaining the first blood parameter comprises performing a pH analysis.

In one or more example methods, the obtaining the first blood parameter can include using a hemolysis detector to analyze a plasma phase of the blood sample, e.g. for detecting lipids or lipid levels in the blood sample. In one or more example methods, multiple sensors, such as optical sensors, and/or image capturers may be used. Thus, multiple different parameters can be obtained from the blood sample prior to preparing the blood sample with reagent. Alternatively, multiple sensors and/or image capturers may be used to obtain and verify the same blood parameter.

The obtaining either the sensor data and/or the image data may be performed via a controller. For example, a user may activate the system to obtain the data. Alternatively, the obtaining either the sensor data and/or the image data may be performed automatically, e.g., as a part of a full CBC cycle. A computer system may determine a particular time, such as an optimal time, to obtain the first blood parameter. Thus, the computer system may be in electronic communication with the sensors and/or image capturer. The computer system may further include a processor to process the obtained sensor and/or image data. The computer system may be able to output the processed data.

After determining the first blood parameter, one or more example methods can include determining a preparation scheme. The preparation scheme can be based on the first blood parameter. The preparation scheme can be one or more preparations schemes. The preparation scheme can be selected (e.g., determined) from a list (e.g., group, table) of different preparation schemes. For example, the preparation scheme can be selected from the list based on the particular first blood parameter.

In one or more example methods, the list can include a plurality, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, or 100 different preparation schemes. In one or more example methods, the list can include greater than 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, or 100 different preparation schemes. In one or more example methods, the list can include less than 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, or 100 different preparation schemes. In one or more example methods, the list can include from 3-5 different preparation schemes.

In one or more example methods, the preparation scheme can vary depending on the first blood parameters. Thus, different preparation schemes may be relevant to different blood sample parameters. For example, if the blood sample has a high lipid level, the preparation scheme relevant to a blood sample with high lipid content can be selected. Another preparation scheme may be relevant to blood samples with high or low red blood cell content and/or high platelet content. Another preparation scheme may be relevant to low red blood cell content and high protein content. Other iterations of preparation schemes can be used as well. This can allow for different schemes to be used depending on the first blood parameter, providing for more accurate results.

Further, the method can include preparing the blood sample according to the preparation scheme. Different preparation schemes can include different preparation settings as discussed below, which may be relevant to the first blood parameter. Thus, advantageously, one or more of the example methods can focus the preparation settings to properly adjust the preparation settings for the particular parameter(s) of the blood sample. This can lead to accurate and fast hematological results.

For example, the method can include preparing the blood sample with a reagent according to the preparation scheme. In other words, determining a preparation scheme may comprise selecting one or more reagents from a set of reagents for the preparation scheme.

The reagent can be one or more reagents that can be mixed with, e.g., incorporated into, combined with, added into, the blood sample. The reagent can be configured to affect one or more properties of the blood sample. For example, the reagent can be a staining reagent (e.g., stain the blood sample). This can make certain components of the blood, such as white blood cells and platelets, optically visible for analysis. The reagent can be a lysing reagent (e.g., to lyse the blood sample). The lysing can affect the red blood cells. A single reagent can be a lysing reagent and a staining reagent. Multiple reagents could be used as well, with one reagent being a lysing reagent and another being a staining reagent.

In one or more example methods, the reagent could be added to the blood sample along a fluid pathway from the inlet. For example, the system can include a reagent inlet in fluid communication with the pathway. This can be at a T-junction. The reagent inlet can be in fluid communication with a reservoir (e.g., housing, container, storage) for accommodating the reagent. Thus, the reagent can be in fluid communication with the fluid pathway that the blood sample is held within. In one or more example methods, the reagent inlet can include a dose valve for proper addition of reagent to the blood sample. The valve can be controlled by a user, or electronically such as through a computer system or controller as disclosed herein.

In one or more example methods, the method can further include mixing. For example, reagent can be mixed with the blood sample. While adding the reagent to the fluid pathway with the blood sample some mixing may be performed, and it may be advantageous to further mix the blood sample and the reagent to form a mixture. Thus, the system can include a mixer. The mixer may be in fluid communication with or form a part of the fluid pathway. Thus, the blood sample and reagent can pass through the mixer. The mixer can be a helical mixer. For example, the mixer can use a helix principle. The mixer can be a centrifuging mixer and/or a static mixer and/or a high shear mixer and/or a drum mixer. Preferably, the mixer does not activate any components of the blood sample, such as causing consolidation of platelets and thereby causing clotting. The mixer can provide a shear force onto the blood sample and reagent. Increasing certain settings of the mixer, such as discussed below, can increase the likelihood of red blood cell lysis, thus providing for improved hematological analysis. For example, by increasing mixing cycles or mixing speeds, shear forces on the cells are increased, thereby improving red blood cell lysis.

By passing through the mixer, the mixer may mix the reagent with the blood sample. This can form a prepared blood sample and/or a mixture. The mixture may pass through the mixer one or more times, such as back and forth. For example, the blood and reagent may pass through the mixer in a first direction to form the mixture. The mixture then may reverse to a second direction and pass through the mixer again, thereby further mixing the mixture. The mixture may then reverse to the first direction to pass through the mixer a third time. Each pass through the mixer may be known as a cycle.

In one or more example methods, the method can further include incubating, e.g., heating the blood sample and/or reagent. The incubator may be configured to heat a portion of the fluid pathway, thus heating the fluid pathway. The incubator may be located after the mixer. The incubator may be located prior to the mixer.

In one or more example methods, the mixer may also be an incubator. The incubator can be a component of the mixer. Thus, the mixer can be configured to incubate and mix the blood sample and reagent at the same time.

As mentioned above, a preparation scheme may be determined based on the first blood parameter. The preparation scheme may include one or more settings. As discussed below, the preparation scheme may include a volume setting and/or a mixing setting and/or an incubation setting. The preparation scheme may include a volume setting and a mixing setting. The preparation scheme may include a volume setting and an incubation setting. The preparation scheme may include a mixing setting and an incubation setting. The preparation scheme can include any number of settings for different modules and/or components and/or methodologies as would be advantageous in preparing a blood sample for hematological analysis.

In one or more example methods, the preparation scheme may include a volume setting, such as a first volume setting and/or a second volume setting and/or a third volume setting, etc. Thus, the preparation scheme can include a first volume setting. In one or more example methods, the first volume setting can be indicative of a volume of the reagent. In one or more example methods, the first volume setting can be indicative of a total volume of the reagent. In one or more example methods, the first volume setting can be indicative of a volume of the reagent as compared to a volume of the blood sample, such as a first volume ratio. Thus, the preparing the blood sample according to the preparation scheme includes adding the reagent to the blood sample in a volume according to the first volume setting.

The volume of the reagent added to the blood sample can vary based on the blood parameter. For example, the blood sample to reagent ratio can be 1 :1 , 1 :2, 1 :3, 1 :4, or 1 :5. Accordingly, 20mL of a blood sample can have 20, 30, 40, 50, 60, 70, 80, 90, or 100mL of reagent added. In one or more example methods, the blood sample to reagent ratio can be greater than 1 :1 , 1 :2, 1 :3, 1 :4, or 1 :5. In one or more example methods, the blood sample to reagent ratio can be less than 1 :1 , 1 :2, 1 :3, 1 :4, or 1 :5. In particular, the ratio of blood sample to reagent can be significantly below 1 :10000, 1 :200, 1 :100, and 1 :50 as typically required in laboratory settings. In one or more example methods, the blood sample to reagent ratio can be in the range from 1 :1 to 1 :4.

The volume of the reagent added to the blood sample can vary based on the blood parameter. For example, the blood sample to reagent ratio can be 1 :1 , 1 :2, 1 :3, 1 :4, or 1 :5. Accordingly, 20pL of a blood sample can have 20, 30, 40, 50, 60, 70, 80, 90, or 100pL of reagent added. In one or more example methods, the blood sample to reagent ratio can be greater than 1 :1 , 1 :2, 1 :3, 1 :4, or 1 :5. In one or more example methods, the blood sample to reagent ratio can be less than 1 :1 , 1 :2, 1 :3, 1 :4, or 1 :5. In particular, the ratio of blood sample to reagent can be significantly below 1 :10000, 1 :200, 1 :100, and 1 :50 as typically required in laboratory settings.

In one or more example methods, the volume of reagent can be 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100mL. In one or more example methods, the volume of reagent can be less than 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100mL. In one or more example methods, the volume of reagent can be greater than 10, 20, 30, 40, 50, 60, 70, 80, 90, or 10OmL. In one or more example methods, the volume of reagent can be 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100pL. In one or more example methods, the volume of reagent can be less than 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100pL. In one or more example methods, the volume of reagent can be greater than 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100pL.

In one or more example methods, the preparation scheme may include a mixing setting, such as a first mixing setting and/or a second mixing setting and/or a third mixing setting, etc. Thus, the preparation scheme can include a first mixing setting. In one or more example methods, the first mixing setting can be indicative of a mixing configuration. For example, it can be indicative of a mixing configuration for a mixing of the blood sample and the reagent. Thus, the preparing the blood sample according to the preparation scheme includes mixing the blood sample and the reagent according to the first mixing setting.

The mixing setting can include one or more parameters of a mixer. For example, this can include number of mixing cycles (e.g., times that the reagent and blood sample pass through the mixer). In one or more example methods, the mixing setting can be 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10 cycles. In one or more example methods, the mixing setting can be less than 2, 3, 4, 5, 6, 7, 8, 9, or 10 cycles. In one or more example methods, the mixing setting can be greater than 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10 cycles.

The mixing setting can include a flow velocity of the reagent and blood sample through the mixer. In one or more example methods, the flow velocity can be 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100mL/second. In one or more example methods, the flow velocity can be greater than 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100mL/second. In one or more example methods, the flow velocity can be less than 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100mL/second.

The mixing setting can include a flow velocity of the reagent and blood sample through the mixer. In one or more example methods, the flow velocity can be 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100pL/second. In one or more example methods, the flow velocity can be greater than 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100pL/second. In one or more example methods, the flow velocity can be less than 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100pL/second. The mixing setting can include a mixing time in the mixer. In one or more example methods, the mixing time can be 5, 10, 15, 20, 25, 30, 35, or 50 seconds. In one or more example methods, the mixing time can be greater than 5, 10, 15, 20, 25, 30, 35, or 50 seconds. In one or more example methods, the mixing time can be less than 5, 10, 15, 20, 25, 30, 35, or 50 seconds.

The mixing setting can include one of the mentioned mixing settings, among others. In alternatives, the mixing setting can include two or all of the mentioned mixing settings, among others.

In one or more example methods, the preparation scheme may include an incubation setting, such as a first incubation setting and/or a second incubation setting and/or a third incubation setting, etc. Thus, the preparation scheme can include a first incubation setting. In one or more example methods, the first incubation setting can be indicative of an incubation configuration. For example, it can be indicative of an incubation configuration for the blood sample. Thus, the preparing the blood sample according to the preparation scheme includes incubating the blood sample according to the first incubation setting. In one or more example methods, the preparing the blood sample according to the preparation scheme includes incubating the blood sample and the reagent according to the first incubation setting.

The incubation setting can include one or more parameters of an incubator. For example, this can include an incubation temperature. In one or more example methods, the blood sample and reagent may be incubated at a temperature of 30, 40, 45, 46, 47, 48, 49, 50, or 55°C. In one or more example methods, the blood sample and reagent may be incubated at a temperature of greater than 30, 40, 45, 46, 47, 48, 49, 50, or 55°C. In one or more example methods, the blood sample and reagent may be incubated at a temperature of less than 30, 40, 45, 46, 47, 48, 49, 50, or 55°C.

It can include an incubation time. In one or more example methods, the blood sample and reagent may be incubated for 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, or 25 seconds. In one or more example methods, the blood sample and reagent may be incubated for greater than 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, or 25 seconds. In one or more example methods, the blood sample and reagent may be incubated for less than 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, or 25 seconds. In one or more example methods, the blood and reagent may not be mixing (e.g., may remain stationary) during the incubation. Alternatively, the blood and reagent may be moving during incubation. The incubation time may vary based on the incubation temperature.

The mixing incubation can include one of an incubation temperature and an incubation time, among others. In alternatives, the incubation setting can include both of an incubation time and an incubation temperature, among others.

In one or more example methods, the preparation scheme may include a reagent identifier of the reagent from a set of available reagent identifiers. Thus, in one or more example methods, the preparing the blood sample with a reagent according to the preparation scheme includes selecting the reagent according to the reagent identifier. For example, a first reagent may have stronger lysing properties than a second reagent. Thus, if stronger lysing may be advantageous, the first reagent may be identified in the preparation scheme.

Advantageously, the preparation scheme can allow for improved hematological analysis. For example, the preparation scheme is configured to achieve full, e.g. sufficient, blood cell lysis and strong white blood cell and/or platelet staining.

Full, e.g. sufficient, blood cell lysis can be achieved when 95, 96, 97, 98, 99, 99.5, 99.6, 99.7, 99.8, 99.9, or 100% of red blood cells are lysed. Full, e.g. sufficient, blood cell lysis can be achieved when less than 95, 96, 97, 98, 99, 99.5, 99.6, 99.7, 99.8, 99.9, or 100% of red blood cells are lysed. Full, e.g. sufficient, blood cell lysis can be achieved when greater than 95, 96, 97, 98, 99, 99.5, 99.6, 99.7, 99.8, or 99.9% of red blood cells are lysed.

Advantageously, the disclosed methods can achieve minimal white blood cell and/or platelet lysing. In one or more example methods, 5, 4, 3, 2, 1 , 0.5, 0.4, 0.3, 0.2, 0.1 , or 0.0% of white blood cells and/or platelets are lysed. In one or more example methods, less than 5, 4, 3, 2, 1 , 0.5, 0.4, 0.3, 0.2, or 0.1 % of white blood cells and/or platelets are lysed. In one or more example methods, greater than 5, 4, 3, 2, 1 , 0.5, 0.4, 0.3, 0.2, 0.1 , or 0.0% of white blood cells and/or platelets are lysed.

Strong white blood cell and/or platelet staining can be achieved when 95, 96, 97, 98, 99, 99.5, 99.6, 99.7, 99.8, 99.9, or 100% of white blood cells and/or platelets are stained.

Strong white blood cell and/or platelet staining can be achieved when less than95, 96, 97, 98, 99, 99.5, 99.6, 99.7, 99.8, 99.9, or 100% of white blood cells and/or platelets are stained. Strong white blood cell and/or platelet staining can be achieved when greater than 95, 96, 97, 98, 99, 99.5, 99.6, 99.7, 99.8, or 99.9% of white blood cells and/or platelets are stained.

Thus, in one or more example methods, the method can include performing a complete blood count (CBC) analysis of the blood sample. This can be done after preparing the blood sample, adding the reagent, and incubating the blood sample and/or mixing the blood sample. The analysis can be performed via a cell measurement component for accommodating the blood sample. The analysis can be performed via artificial intelligence and/or image analysis. The analysis can be performed via a computer system. The analysis can be performed via counting of the white blood cells and/or platelets.

In one or more example methods, the method can further include obtaining a second blood parameter. The second blood parameter can be of a second blood component of the blood sample. The second blood parameter can be of the first blood component of the blood sample. The second parameter may be of the blood sample. Thus, the determining the preparation scheme can be based on the first blood parameter and the second blood parameter. Alternatively, the preparation scheme can be based on the first blood parameter or the second blood parameter.

In one or more example methods, the first blood parameter and the second blood parameter can be different parameters. For example, the first blood parameter can be indicative of a red blood cell content of the blood sample (e.g., hematocrit). The second blood parameter can be indicative of a lipid content of the blood sample. However, any of the above-discussed blood parameters can be used for each of the first blood parameter and the second blood parameter.

In one or more example methods, the method can further include obtaining a third, fourth, fifth, etc. blood parameter. Therefore, the preparation scheme may be based on the first, second, third, fourth, fifth, etc. blood parameter. In one or more example embodiments, the different blood parameters may be ranked. Thus, one parameter may be ranked higher than another parameter. If the two parameters require competing preparation schemes, the preparation scheme associated with the higher ranked parameter may be determined and used for the preparation of the blood sample.

In one or more example methods, the preparing the blood sample with a reagent according to the preparation scheme comprises outputting a preparation indicator indicative of the preparation scheme. The preparation indicator can be output to a computer system in order to make any adjustments to the blood sample as discussed in detail above. Further, the preparation indicator can be output to a user who can manually adjust the blood sample, such as according to the above disclosure. The preparation indicator can be electronically communicated, such as through a wireless or wired connector. In one or more example methods, the preparation indicator can be output to a visual device, such as a monitor and/or screen and/or laptop and/or table and/or phone.

After preparing the blood sample, the prepared blood sample can be analyzed. In one or more example methods, the prepared blood sample can be introduced to a container (e.g., cuvette), which can then be analyzed. For example, the prepared blood sample can be image analyzed and/or sensor analyzed. The container can be a multi-use container. Alternatively, the container can be single use.

Advantageously, one or more example methods can provide advantages for hematological analysis. For example, the overall preparation time before the analysis can be greatly reduced. In one or more example methods, the preparation time can be less than 60 seconds, 55 seconds, 50 seconds, 45 seconds, 40 seconds, 35 seconds, 30 seconds, 25 seconds, 20 seconds, 15 seconds, 10 seconds, or 5 seconds. In one or more example methods, the preparation time can be greater than 60 seconds, 55 seconds, 50 seconds, 45 seconds, 40 seconds, 35 seconds, 30 seconds, 25 seconds, 20 seconds, 15 seconds, 10 seconds, or 5 seconds. Further, the need for mixing and/or incubation may be reduced in turn reducing the risk of damaging or otherwise destroying the blood sample, e.g., by activating platelets in the blood sample.

In one or more example methods, the method may initiate the preparation scheme. As the method is proceeding through the preparations discussed above, such as adding reagent and/or mixing and/or incubation, a new first blood parameter may be received. Alternatively, the method may initiate certain preparations, such as adding reagent and/or mixing and/or incubation, prior to obtaining the first blood parameter, or while partially obtaining the first blood parameter. The first blood parameter and/or the new first blood parameter may indicate that the blood sample is out of scope or cannot be analysed, for example too far outside of a standard blood sample, and/or damaged, such as at least partly clotted, and/or unusable so that the method can further include aborting, e.g. stopping, cancelling, ending, the preparation scheme, and thus the preparation of the blood sample, prior to completing the preparation. The method may further include discarding the blood sample after the aborting, e.g. in accordance with a determination that the blood sample is damaged or unusable. The aborting may be performed automatically. The aborting may be indicated to user, such as at the output. The aborting may be performed manually.

The method then may include receiving a second blood sample and performing one or more of the disclosed methods on the second blood sample. The preparation scheme for the second blood sample may be adjusted based on the first blood parameter and/or the updated first blood parameter received from the original blood sample. The preparation scheme for the second blood sample may not be adjusted based on the first blood parameter and/or the updated first blood parameter received from the original blood sample.

Also disclosed herein is a system for performing (e.g., operating) any one of the methods disclosed herein. The system can include one or more modules (e.g., devices, systems) for the above components. For example, the system can include an inlet module. The system can include a reagent module. The system can include a mixer module. The system can include an incubation module. The mixer module and the incubation module may be the same. The system can include a hematological analysis module. The system can include one or more sensors or sensor modules. The system can include one or more optical sensors or optical sensor modules.

As discussed, the different modules may be operated manually or automatically. For example, the modules may be interconnected electronically, such as to a computer system or controller. The computer system may include wired or wireless connections to the different modules. The computer system may include a processer. The computer system may include one or more controllers. The computer system may control the different modules according to the preparation scheme. Thus, in one or more example methods, a user may input the blood sample and receive the hematological results without needing to take any further action.

In one or more example methods, the computer system can include a computer program product. The computer program product can include a non-transitory computer readable medium. The non-transitory computer readable medium can have thereon a computer program. The computer program can include program instructions. The computer program can be loadable into a data processing unit. The computer program can be configured to cause execution of the steps, processes, and/or modules discussed above. For example, when the computer program is run by a data processing unit. Fig. 1 illustrates an example method of the disclosure. As shown, the method 100 is for preparing a blood sample. The method 100 can be used for hematological analysis, as discussed above. Further, the method 100 can be used at a point-of-care for a patient.

As shown, the method 100 can include obtaining a first blood parameter 102. This can be done from a first blood component of a blood sample. Thus, a blood sample can be received, and from a first blood component of the blood sample, the first blood parameter can be obtained. The first blood parameter can be any number of parameters as discussed herein, such as a red blood cell content, indicative of a plasma content of the blood sample and/or a lipid content of the blood sample.

Following, the method 100 can include determining a preparation scheme 104. The preparation scheme can be based on the first blood parameter received from the obtaining the first blood parameter 102. The preparation scheme may be selected from a number of different preparation schemes, such as shown in Fig. 2. The proper preparation scheme can prepare the blood sample in a way that fast and accurate hematological analysis can be performed.

Based on the preparation scheme, the method 100 can then include preparing a blood sample 106. The blood sample can be prepared in many different ways, such as discussed in detail above. This can include reagent levels, incubation settings, mixing settings, etc.

Optionally, after the preparing the sample 106, the method 100 can include analyzing the blood sample 108. Specifically, hematological analysis can be performed on the blood sample. As an example, a complete blood count (CBC) analysis of the blood sample can be performed after preparing the blood sample, adding the reagent, and incubating the blood sample and/or mixing the blood sample. Advantageously, following method 100, full red blood cell lysis and strong white blood cell and/or platelet staining can be achieved.

Also optionally, the method 100 further includes obtaining a second blood parameter 110 of a second blood component of the blood sample. Thus, the determining the preparation scheme 204 is based on the first blood parameter and the second blood parameter. The first blood parameter can be indicative of a red blood cell content of the blood sample and the second blood parameter can be indicative of a lipid content of the blood sample.

Fig. 2 illustrates a process that can be encompassed within method 100. As shown, the process 200 can start with a first blood parameter 202, such as obtained in step 102. Based on the first blood parameter, a particular preparation scheme can be determined. For example, a preparation scheme can be selected from a list of preparation schemes 201 . The list of preparation schemes 201 can include preparation scheme A 204 and a preparation scheme B 206. Of course, the list of preparation schemes 201 may include significantly more preparation schemes than shown in Fig. 2.

As shown, each of the preparation schemes 204/206 can include different settings, such as a first mixing setting 208, a first incubation setting 210, and/or a first volume setting 212. For example, the first incubation setting 210 of preparation scheme A 204 may include a longer incubation time than the first incubation setting 210 of preparation scheme B 206. Thus, if a longer incubation time may be advantageous for preparing the blood sample based on the first blood parameter, preparation scheme A 204 may be determined and selected. This can provide proper preparing of the blood sample 214, allowing for improved hematological analysis.

In particular, the preparation schemes 204/206 include a first volume setting 212 indicative of a volume of the reagent, and the preparing the blood sample 214 can include adding the reagent to the blood sample in a volume according to the first volume setting 212. The reagent can be a staining and/or lysing reagent.

Further, the preparation schemes 204/206 include a first mixing setting 208 indicative of a mixing configuration for a mixing of the blood sample and the reagent, and the preparing the blood sample 214 includes mixing the blood sample and the reagent according to the first mixing setting 208. The first mixing setting 208 includes one or more of a number of mixing cycles, a flow velocity, and a mixing time.

Additionally, the preparation schemes 204/206 include a first incubation setting 210 indicative of an incubation configuration, such as incubation time and/or incubation temperature, for the blood sample, and the preparing the blood sample 214 includes incubating the blood sample according to the first incubation setting 210. The first incubation setting 210 includes one or both of an incubation temperature and an incubation time.

Fig. 3A illustrates a schematic of a system that can utilize any or all of the abovedisclosed methods herein. As shown, the system 300 can include an inlet (e.g., inlet module) 302. The inlet 302 can be configured to receive a blood sample. The inlet 302 can be connected to a fluid pathway for providing the blood sample through the system 300. As shown, the blood sample may pass through a first sensor 306. The first sensor 306 may be any number of sensors, such as a conductivity/impedance sensor or an absorbance/transmittance/refractive index sensor. The first sensor 306 may obtain image data and/or sensor data of the blood sample. The first sensor 306 may be used to obtain the first blood parameter discussed herein. The first sensor 306 may perform a blood gas analysis and/or a basic metabolic panel analysis. The first sensor 306 may be an optical sensor.

In the system shown in Fig. 3A, the first sensor 306 may include an electrical connection 308 to a computer system 310, such as including a controller. The computer system 310 may then determine a preparation scheme that can be used for preparing the sample. The computer system than may be connected to provide data to a reservoir 312 for accommodating a reagent, and a mixer-incubator 314. Further, the computer system 310 may output 316 the data, such as a first blood parameter and/or a selected preparation scheme. For example, the output 316 may include a preparation indicator indicative of the preparation scheme. This may be output to a display, such as a monitor and/or tablet and/or phone, either through a wireless or wired connection.

Thus, the computer system 310 may control how much reagent is added to the fluid pathway 304 to mix with the blood sample based on the preparation scheme. Further, the computer system 310 may control mixing settings and incubation settings of the mixerincubator 314. As shown, the blood sample may pass through the mixer-incubator 314, and optionally reverse flow direction and pass through the mixer-incubator 314 again.

Once the blood sample has been prepared according to the preparation scheme, the blood sample can pass on to the blood analyzer 318, which can perform hematological analysis on the blood sample. The blood sample can be added into a cell measurement component for use in the blood analyzer 318. After the blood sample has been analyzed, it can be discarded.

Fig. 3B illustrates an alternate configuration of the system 300 as shown in Fig. 3A. Thus, unless mentioned, any and/or all components discussed with respect to Fig. 3A can be included in Fig. 3B. As shown, instead of using the first sensor 306, the system 300 can include a separate flow channel to a blood gas analyzer 320. The blood gas analyzer 320 can provide the first blood parameter as discussed herein. Thus, the blood sample is split in two, and the blood gas analyzer 320 can communicate blood parameter(s) to the computer system 310 and/or the blood analyzer 318. Fig. 4 illustrates a more detailed example system. As shown, the system 400 can include blood sample aspiration and/or pre-heating 402. The blood sample can then pass through an inlet 404 to a fluid pathway 406. The blood sample can approach a T-junction with a first liquid sensor 408/410. The first liquid sensor 408/410 may be a first optical sensor. The T-junction 408 can be in fluid communication with a dosing pump 412, which can provide reagent. The first liquid sensor 410 can obtain the first blood parameter, and the preparation scheme can be determined. The first liquid sensor 410 may be located directly after inlet 404. The first liquid sensor 410 may be or comprise a hematocrit (Het) sensor. There may be an additional Het sensor. In another iteration, a first blood parameter can be obtained during blood sample aspiration and/or pre-heating 402.

Based on the preparation scheme, a particular volume of reagent can be added to the blood sample through the dosing pump 412. The combined reagent and blood sample can then move through the helical mixer 414 to mix the reagent and blood sample to form a mixer. As discussed, the mixture can pass through the helical mixer 414 one or more times. The helical mixer 414 may also incubate the mixture.

Once mixed and incubated according to the preparation scheme, the mixture may pass through a second liquid sensor 416. The second liquid sensor 416 may be a second optical sensor. The second liquid sensor 416 may confirm that the mixture has been properly prepared. The second liquid sensor may not be used in certain implementations.

The mixture can then be passed to a reusable cuvette 418, where it can be analyzed in a blood analyzer 420. This can be, for example, an optical microscope, and hematological analysis can be performed. Once the analysis is finished, the mixture can pass to a waste module 422.

Examples of methods for preparing a blood sample according to the disclosure are set out in the following items:

Item 1 . A method of preparation of a blood sample with a reagent for hematology, the method comprising: obtaining a first blood parameter of a first blood component of the blood sample; determining a preparation scheme based on the first blood parameter; and preparing the blood sample with a reagent according to the preparation scheme. Item 2. Method according to Item 1 , wherein the preparing the blood sample with a reagent according to the preparation scheme comprises outputting a preparation indicator indicative of the preparation scheme.

Item 3. Method according to any one of the preceding Items, wherein the obtaining the first blood parameter of the first blood component of the blood sample comprises obtaining image data and/or sensor data of the blood sample and determining the first blood parameter based on the image data and/or the sensor data.

Item 4. Method according to any one of the preceding Items, wherein the obtaining the first blood parameter comprises performing a blood gas (BG) analysis and/or a basic metabolic panel (BMP) analysis, and determining the first blood parameter based on the blood gas (BG) analysis and/or the basic metabolic panel (BMP) analysis.

Item 5. Method according to any one of the preceding Items, wherein the preparation scheme comprises a first volume setting indicative of a volume of the reagent, and wherein the preparing the blood sample according to the preparation scheme comprises adding the reagent to the blood sample in a volume according to the first volume setting.

Item 6. Method according to any one of the preceding Items, wherein the preparation scheme comprises a first mixing setting indicative of a mixing configuration for a mixing of the blood sample and the reagent, and wherein the preparing the blood sample according to the preparation scheme comprises mixing the blood sample and the reagent according to the first mixing setting.

Item 7. Method according to Item 6, wherein the first mixing setting comprises one or more of a number of mixing cycles, a flow velocity, and a mixing time.

Item 8. Method according to any one of the preceding Items, wherein the preparation scheme comprises a first incubation setting indicative of an incubation configuration for the blood sample, and wherein the preparing the blood sample according to the preparation scheme comprises incubating the blood sample according to the first incubation setting.

Item 9. Method according to Item 8, wherein the first incubation setting comprises one or both of an incubation temperature and an incubation time.

Item 10. Method according to any one of the preceding Items, wherein the reagent is a staining and/or lysing reagent. Item 11. Method according to any one of the preceding Items, wherein the first blood parameter is a red blood cell content, indicative of a plasma content of the blood sample and/or a lipid content of the blood sample.

Item 12. Method according to any one of the preceding Items, wherein the method further comprises obtaining a second blood parameter of a second blood component of the blood sample, wherein the determining the preparation scheme is based on the first blood parameter and the second blood parameter, and wherein the first blood parameter is indicative of a red blood cell content of the blood sample and the second blood parameter is indicative of a lipid content of the blood sample.

Item 13. Method according to any one of the preceding Items, wherein the method comprises performing a complete blood count (CBC) analysis of the blood sample after preparing the blood sample, adding the reagent, and incubating the blood sample and/or mixing the blood sample.

Item 14. Method according to any one of the preceding Items, wherein the preparation scheme is configured to achieve full red blood cell lysis and strong white blood cell and/or platelet staining.

Item 15. Method according to any one of the preceding Items, wherein the first blood parameter is obtained during aspiration of the blood sample.

Item 16. Method according to any one of the preceding Items, wherein the preparation scheme comprises a reagent identifier of the reagent from a set of available reagent identifiers, and wherein preparing the blood sample with a reagent according to the preparation scheme comprises selecting the reagent according to the reagent identifier.

Item 17. A system for adaptive preparation of a blood sample for point of care hematology, the system comprising: a controller; a reservoir for accommodating a reagent; and a cell measurement component for accommodating a blood sample; wherein the system is configured to perform the method according to any one of the preceding Items. Item 18. A computer program product comprising a non-transitory computer readable medium, having thereon a computer program comprising program instructions, the computer program being loadable into a data processing unit and configured to cause execution of the steps according to any of claims 1 through 14 when the computer program is run by the data processing unit.

In a first aspect of the invention, the blood analyzer disclosed in present disclosure is configured to analyze biological fluids, such as, e.g., human, animal, mammalian blood, and/or cell cultures. Moreover, in said further aspect the blood analyzer is substituted by and/or comprises a biological fluid analyzer, such as, e.g., a blood analyzer and/or a cell culture analyzer.

In the first aspect, any disclosed blood sample may be substituted by and/or comprise a biological fluid sample, such, e.g., as a human blood sample, an animal blood sample, a mammalian blood sample, and/or a cell culture sample.

In the first aspect, the method of preparation of a blood sample with a reagent for hematology may be a method of preparation of a biological fluid sample with a reagent for biological fluid analysis

In the first aspect, any disclosed prepared blood sample may be substituted by and/or comprise a prepared biological fluid sample, such, e.g., as a prepared human blood sample, a prepared animal blood sample, a prepared mammalian blood sample, and/or a prepared cell culture sample.

In the first aspect, any disclosed blood parameter may be substituted by and/or comprise a biological fluid parameter, such as human blood parameter, an animal blood parameter, a mammalian blood parameter, and/or a cell culture parameter.

In some embodiments of the first aspect, the cell culture comprises a culture of cells derived from multicellular eukaryotes, such as, e.g., mammalian cells, animal cells, and/or human cells. In some embodiments, the cell culture comprises a culture of cells grown from plant tissue culture, fungal culture, and/or microbiological culture (of microbes).

In the first aspect, a cell may therefore be a mammalian cell, an animal cell, a human cell, a plant tissue cultured cell, a fungal cultured cell, or a microbiologically cultured cell.

The use of the terms “first”, “second”, “third” and “fourth”, “primary”, “secondary”, “tertiary” etc. does not imply any particular order, but are included to identify individual elements. Moreover, the use of the terms “first”, “second”, “third” and “fourth”, “primary”, “secondary”, “tertiary” etc. does not denote any order or importance, but rather the terms “first”, “second”, “third” and “fourth”, “primary”, “secondary”, “tertiary” etc. are used to distinguish one element from another. Note that the words “first”, “second”, “third” and “fourth”, “primary”, “secondary”, “tertiary” etc. are used here and elsewhere for labelling purposes only and are not intended to denote any specific spatial or temporal ordering.

Furthermore, the labelling of a first element does not imply the presence of a second element and vice versa.

It may be appreciated that Figs. 1-4 comprise some modules or operations which are illustrated with a solid line and some modules or operations which are illustrated with a dashed line. The modules or operations which are comprised in a solid line are modules or operations which are comprised in the broadest example embodiment. The modules or operations which are comprised in a dashed line are example embodiments which may be comprised in, or a part of, or are further modules or operations which may be taken in addition to the modules or operations of the solid line example embodiments. It should be appreciated that these operations need not be performed in order presented.

Furthermore, it should be appreciated that not all of the operations need to be performed. The example operations may be performed in any order and in any combination.

It is to be noted that the word "comprising" does not necessarily exclude the presence of other elements or steps than those listed.

It is to be noted that the words "a" or "an" preceding an element do not exclude the presence of a plurality of such elements.

It should further be noted that any reference signs do not limit the scope of the claims, that the example embodiments may be implemented at least in part by means of both hardware and software, and that several "means", "units" or "devices" may be represented by the same item of hardware.

The various example methods, devices, and systems described herein are described in the general context of method steps processes, which may be implemented in one aspect by a computer program product, embodied in a computer-readable medium, including computer-executable instructions, such as program code, executed by computers in networked environments. A computer-readable medium may include removable and nonremovable storage devices including, but not limited to, Read Only Memory (ROM), Random Access Memory (RAM), compact discs (CDs), digital versatile discs (DVD), etc. Generally, program modules may include routines, programs, objects, components, data structures, etc. that perform specified tasks or implement specific abstract data types. Computer-executable instructions, associated data structures, and program modules represent examples of program code for executing steps of the methods disclosed herein. The particular sequence of such executable instructions or associated data structures represents examples of corresponding acts for implementing the functions described in such steps or processes.

Language of degree used herein, such as the terms “approximately,” “about,” “generally,” and “substantially” as used herein represent a value, amount, or characteristic close to the stated value, amount, or characteristic that still performs a desired function or achieves a desired result. For example, the terms “approximately”, “about”, “generally,” and “substantially” may refer to an amount that is within less than or equal to 10% of, within less than or equal to 5% of, within less than or equal to 1% of, within less than or equal to 0.1% of, and within less than or equal to 0.01% of the stated amount. If the stated amount is 0 (e.g., none, having no), the above recited ranges can be specific ranges, and not within a particular % of the value. For example, within less than or equal to 10 wt./vol. % of, within less than or equal to 5 wt./vol. % of, within less than or equal to 1 wt./vol. % of, within less than or equal to 0.1 wt./vol. % of, and within less than or equal to 0.01 wt./vol. % of the stated amount.

Although features have been shown and described, it will be understood that they are not intended to limit the claimed invention, and it will be made obvious to those skilled in the art that various changes and modifications may be made without departing from the spirit and scope of the claimed invention. The specification and drawings are, accordingly to be regarded in an illustrative rather than restrictive sense. The claimed invention is intended to cover all alternatives, modifications, and equivalents.

LIST OF REFERENCES

100 method of preparing a blood sample for hematological analysis

102 obtaining a first blood parameter

104 determining a preparation scheme

106 preparing a blood sample

108 optionally analyzing a blood sample

110 obtaining a second blood parameter

200 process of preparing a blood sample

201 list of preparation schemes

202 first blood parameter

204 preparation scheme a

206 preparation scheme b

208 first mixing setting

210 first incubation setting

212 first volume setting

214 preparing the blood sample

300 system

302 inlet

304 fluid pathway

306 first sensor

308 electrical connection

310 computer system

312 reservoir

314 mixer-incubator

316 output

318 blood analyzer

320 blood gas analyzer

400 system

402 sample aspiration and/or pre-heating

404 inlet

406 fluid pathway

408 T-junction

410 first liquid sensor

412 dosing pump

414 helical mixer

416 second liquid sensor reusable cuvette blood analyzer waste module