Optics: measuring and testing – Blood analysis
Reexamination Certificate
1999-09-03
2001-07-31
Font, Frank G. (Department: 2877)
Optics: measuring and testing
Blood analysis
C356S040000
Reexamination Certificate
active
06268910
ABSTRACT:
FIELD OF INVENTION
This invention relates to spectrophotometry and the spectrophotometric analysis of plasma expressed from donor blood bags. In particular, this invention relates to a method and apparatus for providing a rapid non-destructive measurement of substances called interferents which compromise plasma integrity, by measurement of absorbance or reflectance. Furthermore, the spectrophotometric measurements are made after the plasma is expressed from the primary blood donor bags, without altering the sterility of the blood components.
BACKGROUND OF INVENTION
Blood is usually donated into sterile plastic bags which contain anticoagulants. These bags (“blood bags”) are connected to one or more similar bags by plastic tubing in a closed system for maintaining sterility. After centrifugation of whole blood contained in a primary collection bag, plasma or plasma plus platelets can be separated from red blood cells in the bag: a higher centrifugal force can separate all cellular elements from the plasma, and a lower centrifugal force can separate the plasma plus platelets from the red cells; the plasma plus platelets can then be subjected to higher centrifugal force in order to separate the platelets from the plasma. Therefore, if separation of plasma, platelets, and red cells is required, a two-step centrifugation is necessary, with a primary blood bag linked to two “satellite” bags in series. If separation of all cellular elements from plasma is required, a single-step centrifugation is necessary, with the primary blood bag linked to one satellite bag. In both cases, plasma will be contained in the last bag having transferred to this last blood bag via plastic tubing from the other bags.
Plasma is used frequently for transfusion to treat clotting disorders, to expand blood volume, to treat shock due to plasma loss in burns or hemorrhage. Plasma is also used frequently to prepare plasma substances, e.g., clotting factors, and other proteins like albumin. This process is referred to as plasma fractionation. The plasma used must not have excessive amounts of hemolysis, turbidity or bile pigments. Since donors are usually healthy, elevated bile pigments is not expected.
Blood chemistry tests are routinely performed on the serum or plasma of whole blood. In a routine assay, red blood cells are separated from plasma by centrifugation, or red blood cells and various plasma proteins are separated from serum by clotting prior to centrifugation. Many tests conducted on plasma or serum samples employ a series of reactions which terminate after the generation of chromophores which facilitate detection by spectrophotometric measurements at one or two wavelengths. Elevated Hb in the blood, i.e., haemoglobinemia, can be due to disease states and as a result of specimen collection and handling. Elevated bile pigmentscan be due to disease states. Increased lipid particles in the blood, also known as hyperlipidemia, can be due to disease states and dietary conditions.
Measurement of interfering substances prior to conducting such blood tests is important in providing meaningful and accurate test results. Haemoglobin (Hb), bile pigments, namely bilirubin (BR) and biliverdin (BV) and light-scattering substances like lipid particles are typical substances which will interfere with, and affect spectrophotometric and other blood analytical measurements. Such substances are referred to as interferents. Although blood is screened for the presence of several viruses, there is no test which provides 100% assurance of the absence of these viruses, and there are still other harmful viruses which are never tested for. In order to increase assurance that harmful viruses are eradicated if present, viral inactivation processes are being developed. One method used for inactivating viruses in plasma is the addition of methylene blue (MB) to the plasma. MB is highly chromogenic and must also be regarded as an interferent. In fact, if a sample is sufficiently contaminated with interferents, tests are normally not conducted as the results will not be reliable.
In blood banking, plasma with compromised integrity will be discarded. Plasma specimen integrity is an essential part of quality assurance as it directly affects the accuracy of test results, and the suitability of the plasma for transfusion or fractionation. Measurement of MB provides additional assurance that the plasma contains the required amount of MB.
Spectrophotometric measurement typically employs infrared (IR) or near infrared radiation (NIR) to assess the concentration of various constituents in a blood sample. Examples of photometric measurements using containers which hold a blood sample are disclosed in U.S. Pat. Nos. 5,291,884; 5,288,646; 5,066,859; and 5,366,903.
U.S. Pat. No. 5,366,903 discloses a sampling device which allows photometric quantitative determination of an analyte in whole blood. The device overcomes the problems of having blood cells in a blood sample by effectively “squeezing out” red blood cells and providing a small volume of sample, free of red blood cell material, from which particular analytes can be measured.
Other applications of photometric methodology include non-invasive determinations of analyte concentrations such as described in U.S. Pat. Nos. 5,360,004; 5,353,790; and 5,351,685. DE 195 30 969A describes a system in which blood contained in a bag is passed to a satellite bag for separation of thrombocyte concentrate from the rest of the plasma. A photometer 10, 18 is used to detect when the first eryathrocytes arrive thereat, at which time valve 8 is closed. EP 0 706 043A discloses the spectroscopic measurement of a liquid sample contained in a transparent plastics bag 14 using optical fibre bundles to lead light into and out from the bag support 12. U.S. Pat. No. 4,522,494 relates to the assessment of the viability of platelets in a transparent flexible blood storage bag. Light from a laser beam is passed into the bag, supported between glass plates 18, 24, and scattered light is measured. U.S. Pat. No. 4,675,019 describes a blood bag having tablets attached to the walls to define an optical path through which light can be passed to measure platelet viability. However none of these documents discloses a method of measuring interferents in the plasma or serum of a blood sample, in order to assess specimen integrity with respect to blood tests, plasma transfusion, or plasma fractionation.
Current methods used for detecting haemoglobinemia, bilirubinemia, biliverdinemia and lipemia or turbidity utilize visual inspection of the specimen with or without comparison to a coloured chart. It is to be understood that those practising in the field use the terms lipemia and turbidity interchangeably. This is because lipemia is the major cause of turbidity in serum or plasma. In blood banking, turbidity is assessed by the ability to read print on a paper placed behind a plasma bag.
Screening of plasma specimens by visual inspection is semi-quantitative at best, and highly subjective. Furthermore, visual inspection of plasma specimens is a time consuming, rate limiting process. Consequently, state-of-the-art blood analyzers in fully and semi-automated laboratories, and automated blood banking facilities cannot employ visual inspection of specimens.
Other methods to assess specimen integrity employ direct spectrophotometric measurement of a diluted sample in a special cuvette. However, such methods are not rapid enough for screening samples. In order to obtain a measurement of the sample of the plasma or serum, specimen tubes must be uncapped, a direct sample of the specimen taken and diluted prior to measurement. Each of these steps is time-consuming and requires disposable cuvettes. In blood banking, sterile techniques must be practised, especially when blood products are not used promptly. Maintaining a closed system is necessary to avoid bacterial contamination, hence any screening for interferents must be performed with the bag-tubing system intact. Removing a segment of the tubing linking the blood/plasma bags by hea
Given Douglas George
Samsoondar James
Bereskin & Parr
CME Telemetrix Inc.
Font Frank G.
Stafira Michael P.
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