CA2117916A1

CA2117916A1 - Apparatus for analysing blood and other samples

Info

Publication number: CA2117916A1
Application number: CA 2117916
Authority: CA
Inventors: Roger Clampitt; Stephen Hazelwood; Donald Wilson Macdonald
Original assignee: Individual
Current assignee: ZYNOCYTE Ltd
Priority date: 1993-02-11
Filing date: 1994-02-10
Publication date: 1994-08-18
Also published as: AU6005594A; WO1994018557A1; GB9302673D0; EP0635131A1

Abstract

2117916 9418557 PCTABS00033 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

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WO94/18557 pcTlGs94loo27 l ~Apparatus For Analvsinq Blood And Other SamPles"

3 This invention relates primarily to an auto-centrifuge 4 analyser and associated diagnostic equipment such as S for use by veterinary and medical practitioners. The 6 invention is particularly useful for use in surgeries, 7 offices, clinics, hospitals and so on, and largely 8 adapted to perform haematology analysis. However, the 9 invention also fihds application in the analysis of other samples, including urine, river water and so on.

12 Information relating to the haematological status of a 13 patient during examination is extremely valuable to a 14 practitioner, as it may be incorporated immediately lS with other observations into the establishment of a 16 diagnosis. However, in the past this has rarely ~een 17 possible as samples of blood are usually sent to remote 18 laboratories with results taking up to a week or the l9 like to be obtained. Further disadvantages and complications arise through the damage of the blood 21 during transport and the morphology of cells may change 22 rendering identification difficult or impossible.

24 It is recognised that significant advantage could be , .

WO94/18557 211 191 ~; PCT/GB94/00271 l gained if a practitioner could obtain important

2 diagnostic information while the patient is in the

3 surgery during the period of consultation. This would

4 enable the practitioner to initiate therapy or order further, more detailed investigations based on the 6 immediate results obtained.

8 The total number of white blood cells and the relative 9 proportions of three different types of the cells, namely lymphocytes, neutrophils and eosinophiles is ll valuable to a clinician in the formation of a 12 differential diagnoses in respect of many pathological 13 conditions, especially inflammatory, infective and 14 neoplastic diseases.
.6 A further particulate component of the blood which is 17 of interest to the practitioner is the platelet. These 18 are not cells but are cytoplasmic fragments formed from 19 a specific cell type. Platelets play an important role in blood clotting.

22 It is appreciated that the aforementioned cells and 23 components of blood are not exhaustive of all of which 24 blood is comprised. However, it is considered that the a.orementioned are of great importance to the 26 practitioner in the preliminary investigation of a 27 patient.

29 Existing! procedures for counting and identifying cells in blood include manual procedures, the use of small 31 electronic cell counters and differential 32 centrifugation analysers. In the manual procedure, 33 dilutions of blood are prepared in isotonic solutions, 34 stained and subsequently placed on a haemocytometer.
The red and white cells are then counted by eye using a ; ' ' WO94118557 21 1 7 9 I ~ PCT/GB941~271 1 microscope. The differential white cell count is 2 performed by making a smear of blood on a microscope 3 slide, fixing, staining and identifying and counting up 4 to 400 white blood cells. This procedure is inherently time consuming and few practitioners have the skills to 6 perform the task well. The manual procedure also lacks 7 accuracy and is further hindered by the difficulty in 8 maintaining the necessary equipment clean in a busy 9 practice environment.
11 With small electronic cell counters a carefully diluted 12 blood sample in an electrolyte solution is placed in a 13 plastic container. A probe with a small aperture is 14 then placed in the suspended cells and the cells are drawn through the aperture using a vacuum pump. The 16 electrical resistance across the aperture i~ altered as 17 cells of different size and number pass through. The 18 frequency of the changing resistance indicates the cell 19 numbeir and the magnitude of the change indicates the cell size. Again however, such electronic cell 21 counters are inherent with disadvantages. For example, 22 they are not versatile and generally do not work well 23 for species with small red cells such as sheep and 24 goats~ Similarly, they do not work for species with nucleated red cells such as birds and reptiles. The 26 instruments need to be calibrated and require other 27 special skills for successful operation. The apertures 28 also tend to be blocked by fibrin in the blood samples, 29 thereby reducing efficiency and requiring çontinual maintenance and cleaning. Yet further, the electronic 31 cell counters do not provide a differential count and 32 the manual procedure described hereinbefore must be 33 adopted.

The third existing procedure for counting and :

2l l~(31~ 4 l identifying cells in blood is commonly referred to as 2 differential centrifugation analysers. These analysers 3 work by differential centrifugation of a stained blood 4 sample. The interfaces between the different cell type segments are identified by microscopic examination and 6 the relative proportion of the ce~l types calculated.
7 However again, the system is only really suitable to 8 two species of mammals and so.~e of the required blood 9 parameters are not able to be measured~
ll It may be seen therefore that apparatus heretobefore 12 known for providing assistance in the analysis of blood 13 is not entirely satisfactory, and in fact has been 14 associated with considerable delay and expense in the obtaining of meaningful results.

17 This undesirable situation is also true in the analysis 18 of a variety of samples, and is not limited merely to 19 the area of haematology. It is believed that there is a need for an improved apparatus having universal 21 application in the analysis of, most particularly, 22 liquid samples, many of which relate to veterinary and 23 medical fields. In the past procedures have been too 24 complex, time consuming or expensive and it is therefore an object of the present invention to provide 26 a novel analyser which is able to fulfil the present 27 needs of the practitioner.

29 According to the invent.ion there is provided apparatus for analysing samples, comprising sample carrying 31 means, a centrifuge for rotating a said sample at a 32 predetermined rotational velocity such that centrifugal 33 force separates the various phases or components of the 34 sample, sample reading means for reading or measuring predetermined characteristics of the sample, analysis :

1 means for analysing the data obtained by the sample 2 reading means and display means for displaying data 3 produced by the analysis means relating to the sample.
Preferably, the sample carrying means includes a 6 centrifugal head having slots for supporting respective 7 tubes.
9 Preferably, the sample carrying means also includes a cuvette receptor.

12 Preferably, the sample carrying means also includes a 13 sample tube rotor.

~referably, said tubes may be either blood centrifuge 16 tubes or haematocrit tubes, wherein said blood 17 centrifuge tubes are also adapted for containing urine.

19 The centrifuge may include a DC servomotor and a drive shaft upon which the centrifugal head and sample tube 21 rotor are adapted to be mounted.

23 Preferably, the sample reading means includes a 24 haemoglobin photometer for reading predetermined characteristics relating to the sample contained in a 26 cu~ette positioned in the cuvette receptor, and a 27 polychromatic optical head positioned on a scanning arm 28 enabling radial readings of predetermined 29 characteristics of the sample contained in a tube supported on the centrifugal head. The polychromatic 31 optical head may typically include means for measuring 32 the length of a sample within a tube, an interface 31 detector and à multi-wavelength spectrophotometer.

Desirably, the scanning arm may be pivotably mounted at ,, , W094/18557 2 117 ~ 16 PCT/GB94/00271 1 a position adjacent to the circumference of the 2 centrifugal head such that one end of the arm 3 supporting the polychromatic optlcal head n,ay move from 4 a first position outside of t~hç circumference to a second position within the c~rcumference defined by the 6 centrifugal head. Alternatively, the scanning arm may 7 include a linear track facilitating radial movement of 8 the polychromatic optical head.

The display means may comprise a visual display, such 11 as an LCD screen or a printed output.

13 Preferably, the apparatus also includes a data input 14 means such as a numeric and special function keyboard.
16 The analysis means preferably includes a memory 17 containing diagnostic data interpretation assistance, 18 data comprising analytic reference ranges relevant to 19 the sample being analysed and data comprising recommendations for ~urther testing based on the 21 associated analysis of the sample. The analysis means 22 also includes means for calculating analytical 23 concentrations and interpreting readings and 24 measurements obtained by the sample reading means.
26 Preferably, the tubes are detachable from the cuvette 27 receptor, rotor and centrifugal head and are 28 disposable.

Preferably, said analyser is adapted to be connected to 31 or integral with a pattern recognition means adapted to 32 detect and record the size and morphological 33 characl-eristics of a large number of cells.

An embodiment of the invention will now be described by 2~17916 1 way of example only, with reference to the accompanying 2 figures, in which:

4 Fig. la and lb show pictorial views of an analyser S in a respective closed and open position in 6 accordance with the in~ention, 8 Figs. 2a and 2b show blood centrifuge tubes and 9 haematocrit tubes respecti~ely, 11 Fig. 3 shows a centrifugal head supporting four 12 haematocrit tubes.

14 Fig. 4 shows a rotor assembly with a tube rotor connected, 17 Fig. 5 shows a centrifuge drive assembly, and 19 Fig. 6 shows a folded detector assembly for use in the optical head described in the invention.

22 Referring firstly to Figures la and lb, an auto 23 centrifuge analyser 10 comprises a centrifuge ll, data-24 input means 12, data-display means 13 and a haemoglobin photometer (not shown) contained in the compartment 14.
26 In the embodiment shown in Fig. 1 the data-display 27 means 13 comprises an LED display while the data-input 28 means 12 comprises a numeric and special function key 29 pad.
31 The analyser 10 in Fig. 1 is also provided with a lid 32 15 which enables access to the centrifuge 11, while 33 protecting same when in a closed position from dust or 34 other potential damage.

7 ~

1 An example embodiment of a drive assembly for the 2 centrifuge 11 is shown in Fig. S. A support frame 3 prov des a mounting for a DC servomotor 2 which drives 4 a shaft 8 upon which is mounted a centrifugal head 16.
S The centrifugal head is shown in ~ore detail in Fig. 3.
6 Located just outside the circumference of the 7 centrifugal head 16 is a second`shaft 7 upon which may 8 be pi~otably mounted a scanning arm 17 supporting an 9 optical head for reading predetermined characteristics of samples supported in tubes 22 on the centrifugal 11 head 16. An example embodiment of a scanning arm 17 is 12 also illustrated in Fig. 1.

14 The shaft 8 upon which the centrifugal head 16 is adapted to be mounted may also be used to support a 16 sample tube rotor l. ~eferring to Fig. 4, a sample 17 tube rotor is adapted to support sample tubes 18 while 18 being rigidly connected to the shaft 8 adapted to 19 rotate the centrifugal head 16 and the tube rotor 1.

21 Thus the auto-centrifuge 11 is adapted to enable 22 rotation of at least two different types of tubes, 23 namely and by way of example only, a packed cell volume 24 (PCV) or haematocrit tube supported on the centrifugal head 16 or a conical sample tube, supported in the 26 sample tube rotor 1. These two types of tubes for 27 carrying samples are shown in Figs. 2a and 2b. Fig. 2a 28 shows a centrifuge conical sample tube 21 which is 23 adapted to be located in one of the apertures in the sample tube rotor 1. The tube 21 may be disposable to 31 maintain the integrity of the samples and, by way of 32 example, might approximate a volume capacity of 1.5 33 millilitres. Such a tube may be equally used for the 34 analysis of blood or urine or indeed other types of samples such as river water or beverages, whereby the WO94118SS7 . ~ 1 7gl 6 PCT/GB94/00271 l rotational speed or duration of rotation may be varied 2 in respect of the centrifuge ll. The haematocrit tube 3 22 shown in Fig. 2b is generally of a significantly 4 thinner diameter and is adapted to be located in the slots 3 in the centrifugal head 16. The data-input 6 means 12 may be used to control the rotational velocity 7 of the centrifuge ll to meet the requirements of the 8 analysis test being conducted.

The analyser lO is also provided with an optical head ll mounted on a scanning arm 17. The head comprises a 12 light source adapted to pass light through a sample, 13 and a detector for detecting the non-absorbed light.
14 The head is adapted to measure PCV and other similarly pertinent data, in addition to determining density of 16 the sample film for cell counting and the like, in such 17 circumstances where a contrifugal head 16 similar to 18 that shown in Figure 3 is used.

The analyser lO is adapted to determine the packed cell 21 volume of a sample placed in the haematocrit tube 22 22 by, having spun the sample usin~ the centrifuge ll, 23 using the optical head to measure the total length of 24 the sample column (a) within the tube 22, search for 2S interfaces between the different phases (for example, 26 the plasma and the packed cell fraction) in the 27 centrifuged sample, and then determine the percentage 28 of packed cells (b) in the column (a). The calculated 29 PCV is then displayed by the display means,13 on the front of the analyser lO.

32 The detector assembly generally described at 35 in Fig.
33 6 comprises a housing 30 which supports a mirror 31, a 34 lens assembly 32 and a detector 33. In use, light emitted from light source A is passed through the ~;:

WO94/18557 2117 9 1~ PCT/GB94/00271 l sample which might be located at B and thereafter 2 reflected from the mirror 31 through the lens 32 to the 3 detector 33. The detector signal is then analysed by 4 the analysing means. The screws 34 may be used for adjustment of the mirror 3l. `

7 The centrifuge ll enables a plurality of functions to 8 be performed. For example, it enables separation of 9 red cells from plasma lserum by centrifugation, separation of urine sediment, cells and crystals by ll centrifugation, separation of fats and cells in milk by 12 centrifugation, separation of particles in a water 13 solution and floatation of parasite eggs in a 14 preprepared faecal sample. Additionally, the auto-centrifuge enables a number of tests to be performed 16 which are adapted to supply the clinician with 17 important information in diagnosis and treatment.
18 These tests include, in addition to determination of l9 packed cell volume as discussed hereinbefore, white cell estimates, haemoglobin measurements, erythrocite 21 sedimentation rates, fibrinogen measurement, icterus 22 indeces, haemolosis indeces, lipaenici indeces and main 23 cell haemoglobin concentrations.

The auto-centrifuge may be an integral component of a 26 larger blood cell counter. The auto-centrifuge, for 27 example, may be connected to an imager having a pattern 28 recognition means adapted to detect and record, for 29 example, the size and morphological characteristics of a large number of cells. It is recognised herein that 31 software packages are in existence or may be produced 32 which interpret cell patterns and provide the vast 33 majority of haematological and other information 34 required by practitioners. This would allow the device to perform both red and white blood cell counting, ~117~1~
W094/18557 PCT/GBg4/0027l 1 platelet estimates and many other tests. However, it 2 may also be designed as a stand-alone device adapted to 3 provide essential screening information to the 4 practitioner.

6 Thus, through the use of alternative rotors, such as 7 those shown by way of example and referenced 16 and 1 8 hereinbefore, the analyser lO is adapted to provide 9 pertinent analytic data relating to the sample, together with preparing the sample for further study 11 and analysis, in a particularly shortened time period 12 to that previously experienced by practitioners. The 13 preparatory ability of the analyser includes the 14 preparation of plasma for biochemical analysis, urinary spun deposits, a hae~atocrit stained blood film.
16 Furthermore, it uniquely combines a haemoglobin 17 photometer with a centrifuge to synergistically 18 increase the meaningful results that may be obtained.

The optical head is adapted to move radially in respect 21 to the centrifugal head 16, such that the light source 22 A may pass light to the deflector assembly 35 23 throughout different points along the length of a 24 haematocrit tube 22 located in the slots 3 of the centrifugal head 16. In order to provide this radial 26 movement, the invention provides, in a preferred 27 embodiment, for the scanning arm 17 to be pivotably 28 mounted such that the optical head is able to pass over 29 the full length of a tube 22. An advantage of this pivotal movement is that the arm 17 may be cleared from 31 the centrifugal head 16 when it is desired to position 32 the rotor 1 on the centrifugal head 16. In the 33 preferred embodiment, the arm 17 is U-shaped somewhat 34 similar to a tuning fork, thereby providing a carrier for the light source above the head 16 and a carrier W094/18557 , PCT/GB94/~t71 2 1 17 9 lb 12 l for the detector assembly 35 below the head 16.
3 In an alternative embodimen~, the optical head could be - 4 arranged with one or more~linear tracks or bearings enabling radial movement of the head.

7 Further modifications and improvements may be 8 incorporated without departing from the spirit or scope 9 of the invention herein intended.

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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.

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.

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.

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.