WO1994018557A1

WO1994018557A1 - Apparatus for analysing blood and other samples

Info

Publication number: WO1994018557A1
Application number: PCT/GB1994/000271
Authority: WO
Inventors: Roger Clampitt; Stephen Hazelwood; Donald Wilson Macdonald
Original assignee: Zynocyte Limited
Priority date: 1993-02-11
Filing date: 1994-02-10
Publication date: 1994-08-18
Also published as: GB9302673D0; CA2117916A1; AU6005594A; EP0635131A1

Abstract

An auto-centrifuge analyser (10) combines a centrifuge (11) with a haemoglobin photometer and sophisticated means for analysing predetermined characteristics of samples supported in the centrifuge or photometer to enable the production of diagnostic and treatment information based on the sample being tested in a relatively short period of time.

Description

"Apparatus For Analysing Blood And Other Samples"

This invention relates primarily to an auto-centrifuge analyser and associated diagnostic equipment such as for use by veterinary and medical practitioners . The invention is particularly useful for use in surgeries, offices, clinics, hospitals and so on, and largely adapted to perform haematology analysis. However, the invention also finds application in the analysis of other samples, including urine, river water and so on.

Information relating to the haematological status of a patient during examination is extremely valuable to a practitioner, as it may be incorporated immediately with other observations into the establishment of a diagnosis. However, in the past this has rarely been possible as samples of blood are usually sent to remote laboratories with results taking up to a week or the like to be obtained. Further disadvantages and complications arise through the damage of the blood during transport and the morphology of cells may change rendering identification difficult or impossible.

It is recognised that significant advantage could be gained if a practitioner could obtain important diagnostic information while the patient is in the surgery during the period of consultation. This would enable the practitioner to initiate therapy or order further, more detailed investigations based on the immediate results obtained.

The total number of white blood cells and the relative proportions of three different types of the cells, namely lymphocytes, neutrophils and eosinophiles is valuable to a clinician in the formation of a differential diagnoses in respect of many pathological conditions, especially inflammatory, infective and neoplastic diseases.

A further particulate component of the blood which is of interest to the practitioner is the platelet. These are not cells but are cytoplasmic fragments formed from a specific cell type. Platelets play an important role in blood clotting.

It is appreciated that the aforementioned cells and components of blood are not exhaustive of all of which blood is comprised. However, it is considered that the aforementioned are of great importance to the practitioner in the preliminary investigation of a patient.

Existing procedures for counting and identifying cells in blood include manual procedures, the use of small electronic cell counters and differential centrifugation analysers. In the manual procedure, dilutions of blood are prepared in isotonic solutions, stained and subsequently placed on a haemocytometer. The red and white cells are then counted by eye using a microscope. The differential white cell count is performed by making a smear of blood on a microscope slide, fixing, staining and identifying and counting up to 400 white blood cells. This procedure is inherently time consuming and few practitioners have the skills to perform the task well . The manual procedure also lacks accuracy and is further hindered by the difficulty in maintaining the necessary equipment clean in a busy practice environment.

With small electronic cell counters a carefully diluted blood sample in an electrolyte solution is placed in a plastic container. A probe with a small aperture is then placed in the suspended cells and the cells are drawn through the aperture using a vacuum pump. The electrical resistance across the aperture is altered as cells of different size and number pass through. The frequency of the changing resistance indicates the cell number and the magnitude of the change indicates the cell size. Again however, such electronic cell counters are inherent with disadvantages. For example, they are not versatile and generally do not work well for species with small red cells such as sheep and goats. Similarly, they do not work for species with nucleated red cells such as birds and reptiles. The instruments need to be calibrated and require other special skills for successful operation. The apertures also tend to be blocked by fibrin in the blood samples, thereby reducing efficiency and requiring continual maintenance and cleaning. Yet further, the electronic cell counters do not provide a differential count and the manual procedure described hereinbefore must be adopted.

The third existing procedure for counting and identifying cells in blood is commonly referred to as differential centrifugation analysers. These analysers work by differential centrifugation of a stained blood sample. The interfaces between the different cell type segments are identified by microscopic examination and the relative proportion of the cell types calculated. However again, the system is only really suitable to two species of mammals and some of the required blood parameters are not able to be measured.

It may be seen therefore that apparatus heretobefore known for providing assistance in the analysis of blood is not entirely satisfactory, and in fact has been associated with considerable delay and expense in the obtaining of meaningful results.

This undesirable situation is also true in the analysis of a variety of samples, and is not limited merely to the area of haematology. It is believed that there is a need for an improved apparatus having universal application in the analysis of, most particularly, liquid samples, many of which relate to veterinary and medical fields. In the past procedures have been too complex, time consuming or expensive and it is therefore an object of the present invention to provide a novel analyser which is able to fulfil the present needs of the practitioner.

According to the invention there is provided apparatus for analysing samples, comprising sample carrying means, a centrifuge for rotating a said sample at a predetermined rotational velocity such that centrifugal force separates the various phases or components of the sample, sample reading means for reading or measuring predetermined characteristics of the sample, analysis means for analysing the data obtained by the sample reading means and display means for displaying data produced by the analysis means relating to the sample .

Preferably, the sample carrying means includes a centrifugal head having slots for supporting respective tubes.

Preferably, the sample carrying means also includes a cuvette receptor.

Preferably, the sample carrying means also includes a sample tube rotor.

Preferably, said tubes may be either blood centrifuge tubes or haematocrit tubes, wherein said blood centrifuge tubes are also adapted for containing urine.

The centrifuge may include a DC servomotor and a drive shaft upon which the centrifugal head and sample tube rotor are adapted to be mounted.

Preferably, the sample reading means includes a haemoglobin photometer for reading predetermined characteristics relating to the sample contained in a cuvette positioned in the cuvette receptor, and a polychromatic optical head positioned on a scanning arm enabling radial readings of predetermined characteristics of the sample contained in a tube supported on the centrifugal head. The polychromatic optical head may typically include means for measuring the length of a sample within a tube, an interface detector and a multi-wavelength spectrophotometer.

Desirably, the scanning arm may be pivotably mounted at a position adjacent to the circumference of the centrifugal head such that one end of the arm supporting the polychromatic optical head may move from a first position outside of the circumference to a second position within the circumference defined by the centrifugal head. Alternatively, the scanning arm may include a linear track facilitating radial movement of the polychromatic optical head.

The display means may comprise a visual display, such as an LCD screen or a printed output.

Preferably, the apparatus also includes a data input means such as a numeric and special function keyboard.

The analysis means preferably includes a memory containing diagnostic data interpretation assistance, data comprising analytic reference ranges relevant to the sample being analysed and data comprising recommendations for further testing based on the associated analysis of the sample. The analysis means also includes means for calculating analytical concentrations and interpreting readings and measurements obtained by the sample reading means .

Preferably, the tubes are detachable from the cuvette receptor, rotor and centrifugal head and are disposable.

Preferably, said analyser is adapted to be connected to or integral with a pattern recognition means adapted to detect and record the size and morphological characteristics of a large number of cells.

An embodiment of the invention will now be described by way of example only, with reference to the accompanying figures, in which:

Fig. la and lb show pictorial views of an analyser in a respective closed and open position in accordance with the invention,

Figs. 2a and 2b show blood centrifuge tubes and haematocrit tubes respectively,

Fig. 3 shows a centrifugal head supporting four haematocrit tubes.

Fig. 4 shows a rotor assembly with a tube rotor connected,

Fig. 5 shows a centrifuge drive assembly, and

Fig. 6 shows a folded detector assembly for use in the optical head described in the invention.

Referring firstly to Figures la and lb, an auto centrifuge analyser 10 comprises a centrifuge 11, data- input means 12, data-display means 13 and a haemoglobin photometer (not shown) contained in the compartment 14. In the embodiment shown in Fig. 1 the data-display means 13 comprises an LED display while the data-input means 12 comprises a numeric and special function key pad.

The analyser 10 in Fig. 1 is also provided with a lid 15 which enables access to the centrifuge 11, while protecting same when in a closed position from dust or other potential damage. An example embodiment of a drive assembly for the centrifuge 11 is shown in Fig. 5. A support frame provides a mounting for a DC servomotor 2 which drives a shaft 8 upon which is mounted a centrifugal head 16. The centrifugal head is shown in more detail in Fig. 3. Located just outside the circumference of the centrifugal head 16 is a second shaft 7 upon which may be pivotably mounted a scanning arm 17 supporting an optical head for reading predetermined characteristics of samples supported in tubes 22 on the centrifugal head 16. An example embodiment of a scanning arm 17 is also illustrated in Fig. 1.

The shaft 8 upon which the centrifugal head 16 is adapted to be mounted may also be used to support a sample tube rotor 1. Referring to Fig. 4, a sample tube rotor is adapted to support sample tubes 18 while being rigidly connected to the shaft 8 adapted to rotate the centrifugal head 16 and the tube rotor 1.

Thus the auto-centrifuge 11 is adapted to enable rotation of at least two different types of tubes, namely and by way of example only, a packed cell volume (PCV) or haematocrit tube supported on the centrifugal head 16 or a conical sample tube, supported in the sample tube rotor 1. These two types of tubes for carrying samples are shown in Figs. 2a and 2b. Fig. 2a shows a centrifuge conical sample tube 21 which is adapted to be located in one of the apertures in the sample tube rotor 1. The tube 21 may be disposable to maintain the integrity of the samples and, by way of example, might approximate a volume capacity of 1.5 millilitres. Such a tube may be equally used for the analysis of blood or urine or indeed other types of samples such as river water or beverages, whereby the rotational speed or duration of rotation may be varied in respect of the centrifuge 11. The haematocrit tube 22 shown in Fig. 2b is generally of a significantly thinner diameter and is adapted to be located in the slots 3 in the centrifugal head 16. The data-input means 12 may be used to control the rotational velocity of the centrifuge 11 to meet the requirements of the analysis test being conducted.

The analyser 10 is also provided with an optical head mounted on a scanning arm 17. The head comprises a light source adapted to pass light through a sample, and a detector for detecting the non-absorbed light. The head is adapted to measure PCV and other similarly pertinent data, in addition to determining density of the sample film for cell counting and the like, in such circumstances where a contrifugal head 16 similar to that shown in Figure 3 is used.

The analyser 10 is adapted to determine the packed cell volume of a sample placed in the haematocrit tube 22 by, having spun the sample using the centrifuge 11, using the optical head to measure the total length of the sample column (a) within the tube 22, search for interfaces between the different phases (for example, the plasma and the packed cell fraction) in the centrifuged sample, and then determine the percentage of packed cells (b) in the column (a) . The calculated PCV is then displayed by the display means 13 on the front of the analyser 10.

The detector assembly generally described at 35 in Fig. 6 comprises a housing 30 which supports a mirror 31, a lens assembly 32 and a detector 33. In use, light emitted from light source A is passed through the sample which might be located at B and thereafter reflected from the mirror 31 through the lens 32 to the detector 33. The detector signal is then analysed by the analysing means. The screws 34 may be used for adjustment of the mirror 31.

The centrifuge 11 enables a plurality of functions to be performed. For example, it enables separation of red cells from plasma lserum by centrifugation, separation of urine sediment, cells and crystals by centrifugation, separation of fats and cells in milk by centrifugation, separation of particles in a water solution and floatation of parasite eggs in a preprepared faecal sample. Additionally, the auto- centrifuge enables a number of tests to be performed which are adapted to supply the clinician with important information in diagnosis and treatment. These tests include, in addition to determination of packed cell volume as discussed hereinbefore, white cell estimates, haemoglobin measurements, erythrocite sedimentation rates, fibrinogen measurement, icterus indeces, haemolosis indeces, lipaenici indeces and main cell haemoglobin concentrations.

The auto-centrifuge may be an integral component of a larger blood cell counter. The auto-centrifuge, for example, may be connected to an imager having a pattern recognition means adapted to detect and record, for example, the size and morphological characteristics of a large number of cells. It is recognised herein that software packages are in existence or may be produced which interpret cell patterns and provide the vast majority of haematological and other information required by practitioners. This would allow the device to perform both red and white blood cell counting, platelet estimates and many other tests. However, it may also be designed as a stand-alone device adapted to provide essential screening information to the practitioner.

Thus, through the use of alternative rotors, such as those shown by way of example and referenced 16 and 1 hereinbefore, the analyser 10 is adapted to provide pertinent analytic data relating to the sample, together with preparing the sample for further study and analysis, in a particularly shortened time period to that previously experienced by practitioners. The preparatory ability of the analyser includes the preparation of plasma for biochemical analysis, urinary spun deposits, a haematocrit stained blood film. Furthermore, it uniquely combines a haemoglobin photometer with a centrifuge to synergistically increase the meaningful results that may be obtained.

The optical head is adapted to move radially in respect to the centrifugal head 16, such that the light source A may pass light to the deflector assembly 35 throughout different points along the length of a haematocrit tube 22 located in the slots 3 of the centrifugal head 16. In order to provide this radial movement, the invention provides, in a preferred embodiment, for the scanning arm 17 to be pivotably mounted such that the optical head is able to pass over the full length of a tube 22. An advantage of this pivotal movement is that the arm 17 may be cleared from the centrifugal head 16 when it is desired to position the rotor 1 on the centrifugal head 16. In the preferred embodiment, the arm 17 is U-shaped somewhat similar to a tuning fork, thereby providing a carrier for the light source above the head 16 and a carrier for the detector assembly 35 below the head 16.

In an alternative embodiment, the optical head could be arranged with one or more linear tracks or bearings enabling radial movement of the head.

Further modifications and improvements may be incorporated without departing from the spirit or scope of the invention herein intended.

Claims

1 Apparatus for analysing samples, comprising sample carrying means, centrifuge for rotating a said sample at a predetermined rotational velocity such that centrifugal force separates the various phases or components of the sample, sample reading means for reading or measuring predetermined characteristics of the sample, analysis means for analysing the data obtained by the sample reading means and display means for displaying data produced by the analysis means relating to the sample.

2 Apparatus as claimed in Claim 1 wherein the sample carrying means includes a centrifugal head having slots for supporting respective tubes.

3 Apparatus as claimed in Claim 1 or Claim 2 wherein the sample carrying means also includes a cuvette receptor.

4 Apparatus as claimed in any one of the preceding Claims wherein the sample carrying means also includes a sample tube rotor.

5 Apparatus as claimed in Claim 2 or Claim 4 wherein the tubes may be either blood centrifuge tubes or haematocrit tubes, wherein said blood centrifuge tubes are also adapted for containing urine.

6 Apparatus as claimed in any one of the preceding Claims wherein the centrifuge includes a DC servomotor and a drive shaft upon which the centrifugal head and sample tube rotor are adapted to be mounted.

7 Apparatus as claimed in any one of the preceding Claims wherein the sample reading means includes a haemoglobin photometer for reading predetermined characteristics relating to the sample contained in a cuvette positioned in the cuvette receptor, and a polychromatic optical head positioned on a scanning arm enabling radial readings of predetermined characteristics of the sample contained in a tube supported on the centrifugal head.

8 Apparatus as claimed in Claim 7, wherein the polychromatic optical head includes means for measuring the length of a sample within a tube and an interface detector and a multi-wavelength spectrophotometer.

9 Apparatus as claimed in Claim 7 or Claim 8 wherein the scanning arm is pivotably mounted at a position adjacent to the circumference of the centrifugal head such that one end of the arm supporting the polychromatic optical head may move from a first position outside of the circumference to a second position within the circumference defined by the centrifugal head.

10 Apparatus as claimed in Claim 7 or Claim 8, wherein the scanning arm is mounted on a linear track facilitating radial movement of the polychromatic optical head.

11 Apparatus as claimed in any one of the preceding Claims, wherein the display means comprises a visual display, such as an LCD screen or a printed output .

12 Apparatus as claimed in any one of the preceding Claims also including data input means.

13 Apparatus as claimed in any one of the preceding Claims, wherein the analysis means includes a memory containing diagnostic data interpretation assistance, data comprising analytic reference ranges relevant to the sample being analysed and data comprising recommendations for further testing based on the associated analysis of the sample.

14 Apparatus as claimed in any one of Claims 2-13, wherein the tubes are detachable from the cuvette receptor, rotor and centrifugal head and are disposable.

15 Apparatus as claimed in any one of the preceding Claims, which is adapted to be connected to or integral with a pattern recognition means for detecting and recording the size and morphological characteristics of a large number of cells.