Chemical coding method

BACKGROUND OF THE INVENTION

This invention relates to material coding and, more specifically, relates to coding of clinical laboratory specimens which are analyzed in large numbers.

In clinical laboratories, it is necessary that records be made which relate identification of the source of the specimens to be analyzed with the results of the analysis of ₂₅the specimens. If errors are introduced into the records new specimens have to be obtained and the tests must be repeated. This can result in ill will for the clinical laboratory from its clients with possible loss of their patronage as well as serious delay of needed treatment g₀for the sick.

At present, many clinical laboratories are automated. That is, such laboratories are equipped with instrumentation capable of analyzing and automatically reading out and printing the test results on appropriate electronic ₃₅data processing equipment. Various methods are presently used in these clinical laboratories for maintaining accurate records. Included in these methods is the punching of IBM cards at the laboratory from hand-entered data obtained, for example, from labels attached to speci- 40 men containers which have been filled out by physicians, clients or from data hand-entered by laboratory personnel. These data cards are then the means by which the electronically recorded test data are related to the individual patient and ordering physician. Errors are an 45 inherent characteristic of these methods since they require substantial transposing of information and data from one source to another. As noted above, these errors can lead to serious consequences.

SUMMARY OF THE INVENTION

This invention comprises a method for identifying or coding containers and their contents comprising adding chemical identifiers, in predetermined amounts, to each container, so that at the time the container contents are _5Sanalyzed the chemical identifiers disclose a number uniquely associated with the container and its contents. The chemical identifiers employed in this invention are inert to the container contents or specimens and are present in or on the specimens so that all representative sam- βθ pies from each specimen contain an equal amount of the identifiers.

During the analysis of the contents of each coded container, the concentration of each chemical identifier in the container is also determined, stored and printed (if _6gautomatic equipment is used) along with an analysis of the container contents for the purpose of uniquely identifying the results.

DESCRIPTION OF THE PREFERRED

EMBODIMENTS 70

This invention is a method for coding materials and, particularly, for internally coding containers for clinical laboratory specimens. Coding is accomplished by allotting each container a code or identifying number comprising one or more digits (from zero to nine). Different chemical identifiers, which are inert and which are normally not present in the materials, are selected and added thereto, either alone or in a suitable medium, in a manner such that analysis of any sample of the particular material to be tested produces the same identifier concentrations as does any other sample of that material. Where the specimen is a fluid, for example, a blood specimen, the identifier is dispersed through the specimen. The amount of each identifier (except the reference identifier) added to the material is mathematically proportional to the digit which it represents. During analysis of the material, the concentrations of the identifiers in the material are also determined and the code number thereby stored and later reproduced together with the material analysis data.

In one embodiment of the invention, the number of chemical identifiers is equal to the number of digits in the allotted code number so that each identifier represents a digit in the code number and the identifiers are added to a standard amount of material. In another embodiment of this invention an additional or reference identifier in a predetermined amount can be added to the material to ensure accuracy of the code number determination without resorting to the use of standardized amounts of materials for analysis.

This method has particular utility for the coding of clinical laboratory specimens, such as blood, tissue and urine specimens, which can be analyzed by automated equipment linked with computers to provide automatic storage and read-out of the test results.

This invention will hereafter be described with reference to clinical laboratory specimens, although it should be understood that it has wider utility.

More particularly, the method of this invention employs chemical identifiers which must have certain characteristics. They must be inert to the specimens with which they are mixed, and they must be stable in the environments to which they are subjected including those existing during specimen analysis. If they react with the specimens or are unstable during storage or handling, they will be reduced in amount, and, therefore, will not be proportional to the digits which they represent. Hereafter, and in the claims, the term “inert” will be employed to designate inertness of identifiers both to the specimens and to their environment.

Identifiers must also be capable of assay. That is, the amounts of each identifier must be capable of determination and, preferably, in terms of micrograms. The identifiers must not normally be found in human tissues, since the amounts of such identifiers would not then correspond to the digits which they represent and erroneous code numbers would be obtained.

The identifier must be associated with the specimen, in a manner such that analysis of any sample from the specimen can be used to determine the identifier concentration in the total specimen. If the speciment to be identified and analyzed is a solid, such as a metal billet, the identifier could be coated on the billet as a thin film. Each billet sample would then be of established and standardized size, and would necessarily include a standardized section of the billet’s outer surface. On the other hand, if the identifier is to be added to, rather than coated on, the specimen as, for example, with clinical laboratory specimens, the identifiers must be dispersible throughout the specimens in a substantially homogeneous manner, or soluble therein, so that only small samples of the specimens need to be analyzed to

3,733,178 provide the concentration of identifier in the total specimen.

The particular identifiers that may be used will thus depend to some extent upon the specimens to be coded. That is, identifiers which can be successfully employed with one group of specimens may not be useful for coding a different group of specimens. Therefore, to select the correct identifiers, the normal components to be found in the specimens to be analyzed are first determined, and then the identifier is selected with the above described characteristics. Preferably, the identifier will instantly dissolve in any aqueous specimen, including blood specimens.

To code inorganic material, such as, for example, paints, stable organic compounds could be used. To code organic material, such as blood, salts of the lanthanide elements and actinide elements, for example nitrates and chlorides may be used. Salts in these groups are not normally found in blood, are generally inert to blood and dissolve instantly in blood specimens. Furthermore, these salts can be assayed easily (though not solely) in microgram quantities by an atomic absorption spectrophotometer.

With specimens which are to be analyzed for their protein or enzyme content, the lanthanide or actinide may produce some adverse effects, for example, heavy metal effects on proteins. To avoid this problem the salts may be complexed with such complexing agents as j3-diketones, N-substituted iminodiacetic acid, thenoyltrifluoroacetone and ethylenediaminetetraacetic acid in equimolar proportions.

In performing the method of this invention a code or identifying number is allotted to each container. This code number may contain one or more digits. The code number will usually contain a series or plurality of digits, and will hereafter and in the claims be so identified. However, it will be understood that this characterization includes code numbers containing only one or two digits.

Chemical identifiers are next selected as above described. The number of identifiers is at least equal to the number of digits in the code number, with each identifier representing one of the digits in the code number. In another embodiment of this invention one identifier more than the number of digits may be employed, as will later be described. Compositions of each of the identifiers are made up so that all of the identifier compositions have a predetermined and equal concentration of identifier dispersed substantially homogeneously throughout the composition.

The base components, hereafter referred to as “dispersing media,” added to the identifiers to make up the identifier dispersions, may be any components which permit the formation of stable, homogeneous dispersions, provided they have characteristics similar to those set forth above for the identifiers themselves. That is, they must not interfere with analysis of the specimens, or normally be found in the specimens if they represent one of the constituents for which the specimens are analyzed. The identity of the base components will thus also vary with the specimens being analyzed.

In some cases, it is preferred to employ dispersing media which will evaporate and leave a residue of identifiers in the specimen containers prior to addition of specimen to the containers. In these circumstances, the dispersing media may or may not have a relatively high vapor pressure. If they do have a high vapor pressure, steps must be taken to ensure that they remain stable in the environmental conditions in which the identifier compositions are stored, so that evaporation will not prematurely occur to thereby concentrate the identifiers in the identifier compositions. If the dispersing media do not have high vapor pressures, and are thus stable at normal ambient conditions, a vacuum may be used to evaporate the base component, such as in cases where a vacuum is also employed to obtain the specimen.

It is preferred to use very dilute identifier dispersions which decrease the possibility of interference with specimen analysis and make it economically feasible to use otherwise difficult to obtain or expense identifiers. It is also more accurate to transfer samples of the identifier dispersions to the containers when the dispersions are very dilute, since the loss of small amounts of dilute identifier dispersion will, in practice, generally result in a smaller error than when using concentrated dispersions. The foregoing advantages are achieved with dilute identifier dispersions, without decreasing the accuracy of measuring the amount of identifier transferred to the specimen containers during analysis of the specimens.

After the identifier compositions are made up, an allotted code number is, in effect, duplicated by transferring volumes of each identifier composition to the specimen container, so that the volume of each identifier composition so transferred effectively reflects the digit which each identifier represents. For example, the transferred volume of each identifier composition is equal to the digit which it represents, times some unit volume, for example, one milliliter. If the digit is zero, none of the identifier composition representing that digit is transferred to the specimen container. Since all of the identifier compositions have the same concentration, the actual amount of each identifier transferred to a specimen container is directly proportional to the digit in the code number which that identifier represents.

To produce the number 10214, using the foregoing method, five different identifier compositions (A through E) of standard dilution, for example, one microgram per microliter, are first prepared. Identifier composition A would represent that first digit (units), composition B would represent the second digit (tens), and so on to representation of the fifth digit by composition E. The following volumes of identifier compositions are then transferred to a specimen container as follows: one unit volume of composition E; no unit volumes of composition D; two unit volumes of composition C; one unit volume of composition B; and four unit volumes of composition A. Since each of the compositions A through E is diluted to the same extent, the residual amounts of the identifiers themselves are directly proportional to the digits which they represent so that during analysis the concentrations of identifier in the specimen (amounts of identifier per standardized specimen volume) will be determined and can be translated directly into the digits of the code number.

The volumes of identifier can be adjusted to compensate for non-linear or logarithmic characteristics of the analytical equipment. For example, if an instrument reads, as a unit amount, what is in fact a smaller amount at the higher end of the 0-9 scale, while reading a unit amount correctly at the lower end of this scale, the unit volumes of identifier composition transferred to specimen containers can be decreased accordingly, as the digits which they represent increase from 0-9 to thereby supply a linear read-out.

Detection and determination of the amounts of the identifiers may be accomplished by standard laboratory instruments, such as spectrophotometer. In determining the identifier present, the instrument does so by relating the amount of identifier to the total specimen volume. That is, the identifiers are determined as concentrations. If the specimen volume is a constant or standard (identifier volume can be ignored since it is so small), the digit which a particular identifier represents will be correctly determined. However, if less specimen is present than the standard volume, a digit which is higher than the correct digit will result, since the concentration of each identifier will be higher even though the amount of each identifier has not changed.

To overcome this problem, an additional dissimilar identifier (reference identifier), differing from the other chemical identifiers, is selected and an identifier composi

3,733,178 tion of predetermined concentration is prepared. A predetermined quantity of this reference identifier is then transferred to each specimen container, together with the identifiers which represent the code number digits. The concentration of reference identifier in a standard volume 5 of specimen is its reference concentration. Upon analysis of the specimen, the concentrations of each of the digitrepresenting identifiers are first determined. However, the analytical instruments perform the further steps of determining the change in the concentration of the reference jq identifier from its reference concentration (if any) and, thereafter relating this change (if any) to the other identifier concentration to provide corrected values (if necessary).

Although the concentration of reference identifier 15 changes with changes in specimen volume, its change is measured and used to correct identifier concentrations other than the reference, thereby eliminating the effect of specimen volume changes. For example, if the code number digit is two, the standard specimen volume is V, and ₂o the concentration of the reference identifier at specimen volume V is 10, so that there will be a change in all identifier concentrations if the specimen volume is reduced by one-half. The digit will be determined as being 4 in the absence of the reference identifier, since the concen- 25 tration of its identifier in the specimen is now doubled. However, when the reference identifier is present the change in reference identifier concentration from its reference value will be determined as being twice its intended value. Therefore, the digit-representing identifier concen- go tration will be reduced by two to provide the correct concentration and correct digit 2.

Thus, the ratio of digit to reference will be constant, no matter what the factor of dilution, i.e. if code number digit=D and the factor of dilution=F, 35

N—D/R and a · λ and this is true for each code digit.

N.=DJR, N₂=D₂/R, N₃ . . . , Nn—Dn/R. ⁴⁰The identifier compositions can be added to the specimen containers at any time. To facilitate coding it is presently preferred to code the containers at a centralized distribution center at the analytical laboratory. The coded containers can then be sent out to clients, for example. 45 doctors. The latter can then add their specimens to the containers and return them to the laboratory. In conjunction with this coding and distribution method, it is preferred to employ identifier compositions initially containing volatile solvents, which upon evaporation leave only ⁵⁰solid identifier residues in the specimen containers.

To illustrate the manner in which the invention may be carried out, the following examples are given. It is understood, however, that the examples are for the purpose of illustration, and the invention is not to be re- ⁸⁵garded as limited to any of the specific materials or conditions therein.

Example I

The following illustrates the manner in which one cod- ₆₀ing system would operate. Various selected compounds are given code names, and concentrations thereof are then related to numbers. The use of lanthanum nitrate as a reference is also illustrated.

Code name

Praseodymium nitrate P

Gadolinium nitrate G

Samarium nitrate S

Ytterbium nitrate____________, Y

Europium nitrate______________________________ Eγθ

Lanthanum nitrate_________________________,'L ¹ Reference.

Final concentration of each—10, 20, 30, 40, 50, 60, 70, 80, 90,100 7/ml.

To indicate number: 0, 1, 2, 3, 4, 5, 6, 7, 8, 975

To indicate:

‘13604: μΐ. added for evaporation

P 20 20

G 40 40

S 70 70

Y 10 10

E 50 50

L 501 50 ¹ Always this fixed amount.

Example Π

The following illustrates the manner in which the reference compound is used to insure accurate results:

Fixed concentration solutions of 1 j»g./ml. of the compounds shown in Example I are prepared, and appropriate quantities (μΐ.) of each are added to four containers. The liquid portions of the solutions are then evaporated, and held until samples are to be added. A sample of blood is obtained, and four, five, six and seven cc. of it are placed, respectively, in each of the four containers. The number represented by the concentration of the specified compounds is determined as follows:

„ apparent cone, of P.,_„ ,_T

P=-^£i----T------τν X50=Numeral 1 apparent cone, of L „ apparent cone, of G,. , „

G=-^---τ-----jv_FX50=Numeral 3 apparent cone, of L etc.

Thus, it is clear that the variation in volume of a sample will not cause inaccuracy in the method.

Example III

Example I is repeated, except that chloride salts of members of the actinide group are selectively interchanged with the nitrate salts of members of the lanthanide series. Among the members of the actinide group of elements, the following may be conveniently used: Actinium chloride Uranium chloride

Thorium chloride Palladium chloride

Comparable results are achieved.

Example IV

Example II is is repeated, except that actinium chloride is used instead of lanthanum nitrate. Comparable results are achieved.