IE904616A1 - Kit for use in diagnosing maladies - Google Patents

Abstract

A kit (10) for use in diagnosing maladies includes a carrier (26) comprising a plurality of apertures (28) for holding at least one test receptacle (12), wherein the test receptacle (12) has a test substance disposed therein. Each test receptacle (12) has a different test substance, or combination of substances, therein. The kit further includes at least one control receptacle (14). The number of control receptacles preferably relates to the number of tests to be performed, namely one control for every ten tests to be done, with a minimum of five. Preferably, the kit further includes a lysing agent for lysing blood diluent for diluting the volume of blood to be measured. The kit may also include at least one empty receptacle for use in cleaning the equipment used to perform the test.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application is a continuation-in-part of my co-pending application, Ser. No. 363,854, filed June 9, 1989, which was a continuation of my earlier application, Ser. No. 902,313, filed August 28, 1986, now abandoned, which, in turn, was a continuation-in-part of my still earlier application, Ser. No. 547,767, which has now issued as U.S. Pat. No. 4,614,722, on September 30, 1986.

Additionally, this application is related to my earlier application, Ser. No. 913,940, now issued as U.S. Pat. No. 4,788,155, on November 29, 1988.

BACKGROUND OF THE INVENTION The present invention relates to a kit for use in diagnosing the presence or absence of maladies in a subject, and, more particularly, to a kit for use in performing the test described in my prior patents.

In my referenced prior patents, and my referenced co-pending application 15 (the disclosures of which are incorporated herein by reference), I describe a novel method of diagnosing maladies in a subject, by means of comparing the numbers and size distributions of the subject’s blood cells before and after exposure to a substance having a known relationship to the malady for which the subject is being tested.

For ease of description, I refer to my inventive test as being directed to the 20 diagnosis of a presence or absence of a malady. It is intended, however, that that term be interpreted in the broadest sense. The test may be used to ascertain the cause of a known malady. For example, a patient who is known to suffer from migraine headaches, may be said to have had a diagnosis already performed.

However, my test may be used to ascertain the cause of the migraine, such as a food sensitivity. In this sense, then, the test may be used to diagnose a migraine as being a migraine caused by an allergic reaction to a food or a chemical ingested by the patient, as opposed to being a migraine resulting from some other cause.

It is considered unnecessary, in light of the lengthy description of the tests themselves contained in my earlier patents, to describe herein the steps of the test in detail. It is sufficient to summarize that the patented tests describe a methodology for the reliable and objective determination of the presence or absence of a malady in a subject.

Broadly speaking, this methodology includes the steps of: (a) drawing a sample of the subject’s blood; (b) separating the sample into a plurality of separate volumes, each having approximately equal distributions of blood cells therein; (c) exposing at least one (test) volume of the blood to a substance having a predetermined relationship to the malady; (d) measuring the number and/or size distribution of blood cells in a control volume of the subject’s blood; (e) permitting the blood in the test volume to react with the substance; (f) measuring the number and/or size distribution of blood cells in the test volume after reaction has been given the opportunity to occur; and (g) comparing the control and test volume measurements to determine thereby if the subject has the malady for which he or she is being tested.

Again, this is a brief description of the patented test,’ and reference is once more made to the disclosures of the referenced patents for details thereof.

To date, however, there has been no effective and convenient apparatus for performing the tests.

As the test has been performed heretofore, the user thereof was compelled to collect a multitude of receptacles, into each of which he would introduce a selected test substance (except, of course, for the receptacles used for the control volumes). The test substance would be purchased separately, from a different vendor, and different types of test substances would have to be collected from different sources.

For example, food extracts could be purchased from certain sources, while 5 monoclonal antibodies, used for testing for certain types of cancers, would have to be collected from a different source.

Furthermore, while it was known that control samples were needed, it was not known how many samples were optimal for given applications, and so it was uncertain how many control samples should be acquired.

There is therefore a need for a single source of the tools needed to perform the described test, in its various forms.

OBJECTS AND SUMMARY OF THE INVENTION Accordingly, it is an object of the invention to provide a kit for use in performing a test for diagnosing maladies which overcomes the drawbacks of the prior art.

It is a further object of the invention to provide a kit which contains at least one test receptacle and at least one control receptacle for use in performing a diagnosis for a malady.

It is a still further object of the invention to provide a kit for use in 20 diagnosing maladies which includes a number of control samples for performing a broader range of tests for different maladies.

Briefly stated, there is provided a kit for use in diagnosing maladies that includes at least one test receptacle, having a test substance disposed therein. Each test receptacle has a different test substance, or combination of test substances, therein. The kit further includes at least one control receptacle. The number of control receptacles preferably relates to the number of tests to be performed, namely one control for every ten tests to be done, with a minimum of five. Preferably, the kit further includes a lysing agent for lysing blood cells which are not used as part of the test to be performed, and a blood diluent for diluting the volume of blood to be measured. The kit may also include at least one empty receptacle for use in cleaning the equipment used to perform the test, and a carrier to hold the various components of the kit together for ease of transportation.

In accordance with these and other objects of the invention, there is provided a kit for use in diagnosing the presence or absence of a malady in a subject, the kit comprising: a first, test, receptacle; a test substance disposed within the first receptacle, the test substance having a predetermined relationship with the malady; and a second, control, receptacle; whereby separate volumes of the subject’s blood may be placed into the first and second receptacles, for measuring the degree of reaction between the test substance and the blood of the subject.

According to a feature of the invention, there is further provided a kit for use in diagnosing the presence or absence of maladies in a subject, the kit comprising: a first plurality of first, test, receptacles; a second plurality of test substances, at least one of the test substances being disposed in each of the first plurality of the first receptacles, each of the plurality of test substances having a predetermined relationship with at least one malady; and a second, control, receptacle; whereby separate volumes of the subject’s blood may be placed into each of the plurality of the first receptacles and the second receptacle, for measuring the degree of reaction between each of the test substances and the blood of the subject.

According to a still further feature of the invention, there is still further provided a kit for use in diagnosing the presence or absence of maladies in a subject, the kit comprising: a first plurality of first, test, receptacles; a second plurality of test substances, at least one of the test substances being disposed in each of the first plurality of the first receptacles, each of the plurality of test substances having a predetermined relationship with at least one malady; and at least five control receptacles; a third, cleaning, receptacle, for cleaning equipment used in performing the diagnoses; a blood diluent for diluting the blood of the subject during the diagnoses; and a lysing agent, for lysing blood cells in the blood of the subject; wherein the kit includes at least one control receptacle for each ten of the first receptacles; whereby separate volumes of the subject’s blood may be placed into each of the plurality of the first receptacles and the control receptacles, for measuring the degree of reaction between each of the test substances and the blood of the subject.

The above, and other objects, features and advantages of the present invention 10 will become apparent from the following description read in conjunction with the accompanying drawings, in which like reference numerals designate the same elements.

BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a perspective showing the various elements of the inventive kit.

Fig. 2 is an exploded perspective showing a single receptacle of the kit of Fig. 1.

Fig. 3 is a perspective of a secondary embodiment of the inventive kit.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT Referring now to Fig. 1, there is shown, generally at 10, a kit for use in 20 diagnosing maladies in a subject, in accordance with the invention.

In its simplest form, kit 10 includes a plurality of test receptacles 12, and a second plurality of control receptacles 14. Test receptacles 12 and control receptacles 14 differ not at all, except in their respective contents. They are each sealed receptacles made of any sturdy and durable material, such as polystyrene. An exemplary receptacle is shown in Fig. 2, generally at 16.

Receptacle 16 includes a generally cylindrical body 18, and a lid 20. When receptacle 16 is closed, it will be secure against outside contaminants. This will preserve the integrity of receptacle 16. Receptacle 16 also preferably includes a label 22, for identifying contents 24 thereof, i.e. whether it is a test receptacle (such as pictured, where the test substance is a food extract for corn), or a control receptacle, in which case contents 24 will be neutral.

Returning now to Fig. 1, kit 10 further preferably includes a carrier 26, having a plurality of apertures 28 for retaining test receptacles 12 and control receptacles 14.

Carrier 26 may be made of any suitable material for holding test receptacles 12 and control receptacles 14, and its mode of manufacture will be appreciated by those of ordinary skill in the art.

The difference between test receptacle 12 and control receptacles 14 is solely in their respective contents (24 in Fig. 2).

Into each test receptacle 12, a suitable test substance will be placed as its contents (see 24 in Fig. 2). The nature of contents 24 will depend on the type of malady to be diagnosed with that particular test receptacle. As described in the referenced patents, a test may be made for a particular malady in different ways, for example, by adding a suspected reaction-provoking substance (e.g. a suspected food allergen, or a suspected chemical to which the subject is perhaps sensitive) or an antibody specific to that malady (e.g. a monoclonal antibody specific to a cancer for which the subject is tested). For a more detailed discussion of the nature of the reaction which is to be measured by the test, reference is made to U.S. Pat. No. 4,778,155, col. 9, line 27- col. 10, line 5. It will also be appreciated that the predetermined relationship may be that a ttest substance may cause a reaction, and the test may be performed, then, to determine if the test substance in fact has caused the suspected reaction.

The manner in which any particular substance is to be placed into a test receptacle 12 will depend on the nature of the substance. For example, where the test substance is to be a food extract, or a mold, to test for an allergic reaction to the food, very little extract (on the order of a few milligrams) is needed to perform the test effectively. This amount of material is difficult to handle, and so it is preferred that the test substance be carried on a carrier medium. This preference is compounded, in that the extract should be in a stable state, i.e. non-reactive with the environment, particularly with respect to moisture and/or air.

A stable test substance may be fabricated by preparing a solution containing the extract and a suspension medium, such as a mixture of equal parts glycerine and water. The preferred solution would have one part extract to nine parts suspension medium by weight. Once the solution is mixed, approximately 10 microliters of the solution is delivered to the carrier, which in this embodiment is preferably a nylon disk.

The disk is then rapidly frozen. At that point, the liquid portion of the solution, in the form of ice, is removed by sublimation, under a high vacuum, at a low temperature, appx. 50 degrees below zero Celsius.

It is here noted that this method of manufacture is specific to the case of food extracts. In the case of other types of test substances, the general procedure would be the same, but the precise proportions of test substance to suspension medium may differ. That would be a matter of some minor experimentation, well within the scope of one of ordinary skill.

It is here also explicitly noted that the test substance need not be a pure substance. For example, it may be desired to test for reactions caused by a combination of medications in a patient, and so the test substance could be a combination of the two (or more) medicines.

It will also be appreciated that this is but one method of preparing test receptacles 12. It would be possible to carry test substances on any suitable, neutral, medium, such as a plastic pellet, or even on the floor of the receptacle itself, if the receptacle is so formed as to permit such manufacture. Those of ordinary skill in the art will appreciate that the mode of manufacture of test receptacles 12 and control receptacles 14 will be strictly a matter of design choice, within the purview of such an ordinarily skilled person. It will be further appreciated that the precise details of the shape and construction of test and control receptacles 12 and 14, respectively, will depend on the intended application. The receptacles must conform to the intended use.

This, too, is a minor design choice, which those of ordinary skill will be able to determine for their intended use.

An important factor in the manufacture of kit 10 is that the contents of each test receptacle 12 and control receptacle 14 should be identical, but for the inclusion of the test substance in the test receptacle. In other words, even though the test substance is carried on a carrier medium which is believed to be neutral with respect to the subject’s blood, that carrier medium should also be placed in control receptacles 14 as well, in case there is any reaction between that medium and the subject’s blood. Additionally, it assists in avoiding any potential problem in measurement, by ensuring that the volume of material in each type of receptacle is identical.

As to the relative number of test and control receptacles 12 and 14, respectively, it is preferred that at least five control samples be used. In practice, different tests are performed sequentially, not in parallel. This means that each measurement is performed at a slightly different time. Where a number of tests are to be performed, possibly over one hundred in some instances, the difference in time between the first measurement and the final measurement could be as much as an hour or more. If the control specimen is analyzed first, it may have different characteristics than if it were measured last, since, even in a non-reactive situation, a small percentage of blood cells of some patients, in certain instances may deteriorate over time.

Furthermore, it is now preferred that the comparisons be made on the basis of correlation to a standard deviation from the expected results, and the use of an average of several control samplings renders a more accurate result.

These reasons for false readings may be avoided by use of several control samples. For example, if control samples are prepared at different intervals, and the test samples are compared with the control sample nearest in time, then more accurate readings are possible. Furthermore, since the test results are comparative, an average of several control readings may provide a better average of test results, leading to more accurate readings.

After experimentation, it has been determined that, in the currently preferred testing protocol, at least one control measurement should be taken for every ten tests performed, with a minimum of five control samples. This may differ when, over time, different equipment becomes available with either greater accuracy, or greater speed, so that deterioration becomes less of a factor.

The above description details one preferred embodiment of the invention, namely where the inventive kit includes only test receptacles and control receptacles, carried in a carrier. In some applications, however, it may be also preferred to have other items be made a part of kit 10.

Figure 3 illustrates a supplemental kit, shown generally at 30, which illustrates the additional items which may be a part of the inventive kit.

It may be preferred that supplemental kit 30 be affixed to kit 10, and it may be so manufactured. Here, for simplicity of illustration, it is shown separately. ίο Supplemental kit 30 includes a set of blank receptacles 32, for use in cleaning equipment used to perform the diagnoses, a lysing agent 34 and a blood diluent 36 all carried in a carrier 38, having apertures 40.

Blank receptacles 32 may be used for cleaning the equipment used for 5 performing the diagnosis. As will be readily appreciated, the performance of any test involving medical diagnoses must be done carefully, and so the equipment used must be regularly maintained. Blank receptacles 32 may be used for carrying detergents to place them in the equipment for cleaning, and then carrying the detergents away after cleaning.

As noted, in some applications it is necessary to lyse certain blood cells so that measurements may be made. In these applications, lysing agent 34 would be useful. It is preferred that the active lysing agent (for example, Saponin, from Sigma Chemical Co.) be present in a one-per cent solution in bacteriostatic water, in an amount sufficient to perform the tests to be made. Precise measurements may be made in accordance with the protocols set forth in my U.S. patents referenced above.

It will also be noted that the type of lysing agent will depend on the type of blood cell to be lysed, since different measurements may be taken of different types of cells, i.e. red blood cells, white blood cells or platelets.

Similarly, since a blood diluent is used in most applications, it is also preferred that supplemental kit 30 include blood diluent 36, which is preferably a substance which is non-reactive with human blood, and is pH balanced to the acid level of human blood (7.4). Suitable solutions would be a mixture of buffered normal saline, 0.9% sodium chloride buffered to (appx.) pH 7.4 with sodium bicarbonate. The total volume of blood diluent 36 provided would depend on the number of tests (and controls) to be performed, and so will depend on the particular application contemplated for any kit 10 and supplemental kit 30.

The collection of parts described above will permit the efficient and accurate performance of my patented test, by providing, for the first time, all of the components needed to perform the test.

Having described preferred embodiments of the invention with reference to the accompanying drawings, it is to be understood that the invention is not limited to those precise embodiments, and that various changes and modifications may be effected therein by one skilled in the art without departing from the scope or spirit of the invention as defined in the appended claims.

Claims (22)

CLAIMS:

1. A kit for use in diagnosing the presence or absence of a malady in a subject, the kit comprising: a first, test, receptacle; a test substance disposed within said first receptacle, said test substance having a predetermined relationship with the malady; and a second, control, receptacle; whereby separate volumes of the subject’s blood may be placed into said first and second receptacles, for measuring the degree of reaction between said test substance and said blood of the subject.

2. The kit of Claim 1, wherein said test substance is carried in a first volume of a first carrier medium.

3. The kit of Claim 2, wherein said second receptacle includes a second volume of a second carrier medium.

4. The kit of Claim 3, wherein said first and second carrier media are identical.

5. The kit of Claim 3, wherein said first and second volumes are identical.

6. The kit of Claim 1, further comprising: a blood diluent, for diluting said blood of the subject.

7. The kit of Claim 1, further comprising: a lysing agent, for lysing blood cells in said blood of the subject.

8. The kit of Claim 1, further comprising: a third, cleaning, receptacle, for use in cleaning equipment used to perform the diagnosis of the malady. 6 Ί 8 9

9. The kit of Claim 1, further comprising: means for carrying said first and second receptacles.

10. A kit for use in diagnosing the presence or absence of maladies in a subject, the kit comprising: a first plurality of first, test, receptacles; a second plurality of test substances, at least one of said test substances being disposed in each of said first plurality of said first receptacles, each of said plurality of test substances having a predetermined relationship with at least one malady; and a third plurality of second, control, receptacles; whereby separate volumes of the subject’s blood may be placed into each of said first and second receptacles, for measuring the degree of reaction between each of said test substances and said blood of the subject.

11. The kit of Claim 10, wherein at least one of said test substances is carried in a first volume of a first carrier medium.

12. The kit of Claim 11, wherein each of said second receptacles includes a second volume of a second carrier medium.

13. The kit of Claim 12, wherein said first and second carrier media are identical.

14. The kit of Claim 12, wherein said first and second volumes are identical.

15. The kit of Claim 10, further comprising: a blood diluent, for diluting said blood of the subject.

16. The kit of Claim 10, further comprising: a lysing agent, for lysing blood cells in said blood of the subject.

17. The kit of Claim 10, further comprising: a third, cleaning, receptacle, for use in cleaning equipment used to perform the diagnosis of the malady.

18. The kit of Claim 10, further comprising: means for carrying said first and second receptacles.

19. The kit of Claim 10, wherein the kit includes at least one control receptacle for each ten of said test receptacles, with a minimum of five of said control receptacles.

20. A kit for use in diagnosing the presence or absence of maladies in a subject, the kit comprising: a first plurality of test receptacles; a second plurality of test substances, at least one of said test substances being disposed in each of said first plurality of said test receptacles, each of said plurality of test substances having a predetermined relationship with at least one malady; and at least five control receptacles; a cleaning receptacle, for cleaning equipment used in performing the diagnoses; a blood diluent for diluting the blood of the subject during the diagnoses; and a lysing agent, for lysing blood cells in the blood of the subject; wherein the kit includes at least one control receptacle for each ten of said test receptacles, with a minimum of five of said control receptacles; whereby separate volumes of the subject’s blood may be placed into each of said plurality of said test receptacles and said control receptacles, for measuring the degree of reaction between each of said test substances and said blood of the subject. - 15

21. A diagnostic kit substantially as described with reference to and as shown in Figs. 1 and 2 of the accompanying drawings, or with reference to and as shown in Figs. 1 and 2 taken together with Fig. 3 of the accompanying drawings.

22. The features described in the foregoing specification, or any obvious equivalent thereof, in any novel selection.