DE2005964A1 - Method of mixing particulate matter - Google Patents

Description

Patent attorneys Dipl. -Ing. F. Weickmann, 2005 96

Dipl.-Ing. H.Weickmann, Dipl.-Phys. Dr. K. Fincke Dipl.-Ing. F. A. Weickmann, Dipl.-Chem. B. Huber

8 MUNICH 86, DEN IQ, Feb. 1970

PO Box 860 820

MÖHLSTRASSE 22, NUMBER 48 39 21/22

XEROX CORPORATION

Rochester, New York 14603, V. St. A.

Method of mixing particulate matter

The invention relates to a method of mixing particulate matter and, more particularly, to a method for uniformly mixing a slurry containing two or more particulate substances in such a way that finally a homogeneous mixture is achieved. The method is particularly useful for producing a homogeneous mixture of chemicals suitable, whereby the proportions of the chemicals can be used as reagents in analysis processes.

In the microchemical analysis, a method is increasingly used in which not only smaller amounts of sample are required, but also smaller amounts of reagents. If more than one reagent is required, then It is often desirable to use the appropriate reagents to form a powder or tablet reagent to mix with each other, which then to the desired

008836/1864

Time can be entered into the analysis process. In certain cases it may be necessary to use the components in question in quantities to mix with each other that differ greatly from the same mixture. In the most extreme cases, it is Share of one ingredient less than $ 1. Regardless In these extreme cases, different amounts of the respective substances have to be mixed together, which is why it is essential is necessary to achieve a uniform mixture, even if very small proportions of the Mixture correspond to the desired approach. This is particularly important when analyzing individual quantities Reagents are manufactured, as the lack of uniformity in manufacture makes it necessary to that the relevant volume production is abandoned. In the event that the deviation is not immediately apparent, the analytical data obtained with the aid of such substances are imprecise and therefore of no value.

In order to achieve uniform mixtures, attempts have already been made to reduce the respective constituents to a suitable one To reduce the particle size so that an even mixture can then take place. Solids are made by grinding However, brought to the particle size required for such mixing, these substances normally take a sufficiently high electrostatic charge that mixing becomes extremely difficult. It also results in Agglomeration problems, or the substances in question, cannot interact with one another with the desired uniformity be mixed.

The invention is therefore based on the object of a method for uniformly mixing a large number of fine to create divided particulate matter. That new too

009836/1884

The creative process is not supposed to make the difficulty with 'bring yourself out due to the electrostatic Charge. Furthermore, the new procedure to be created a non-reactive, i.e. neutral organic liquid for the formation of a paste from the substances to be mixed with one another Allow fabrics to be used. Besides, that should New processes to be created add dry substances evenly able to mix, like protein-like substances, without making these substances inedible or their chemical reactivity otherwise adversely affect. After all, the new process to be created should be at least two fine allow to mix divided particulate substances, wherein a neutral organic liquid is used to form a pulp from the substances to be mixed together shall be. This liquid should after subsequent removal from the pulp if the evenness of the mixture achieved, is, only a small or no residual part leave behind.

The above problem is solved with the help of a method for mixing particulate substances according to the invention in that from the particulate substances present in a finely divided state using a neutral .Trägerstoffes a pulp is produced that the pulp is kept in motion until it has a homogeneous mixture of substances is formed, and that then the neutral Carrier without influencing the chemical reactivity or the destruction of the uniformity of the mixture of substances is discharged from the pulp in such a way that ultimately only a little or none at all in the mixture of substances Remnants of the carrier material remains.

The method according to the invention has proven to be satisfactory for an even mixture of fairly small quantities a first particulate matter with a much larger one

0098 38/1884

Amount of at least one further nartikelformigen Proven substance. The method according to the invention is satisfactory for the mix of less than 1? o one first fabric with more than $ 99 of a second, fabric or have been used by second substances without making the substances inedible or otherwise the chemical Reactivity of the end product is detrimental to it influence.

The method according to the invention is particularly suitable for the mixing and preparation of analytical reagents as they are required for microchemical analyzes. the However, the invention is not limited to this. With regard to analytical reagents, it should be noted that the Substances can essentially be divided into the following three major categories: Organic Substances, inorganic substances and biological substances such as enzymes, proteins, etc .. It should be evident that these Classification covers a wide range of substances. Some substances have similar properties or problems viewed from the standpoint of mixing or blending. This means that the categories are so large that individual Members of these categories or groups of these members have their own associated mixing problems. Mixing one Mixture containing different chemicals complicates an already complicated case even further as it is difficult can be to find a mixing technique that is suitable for all components together. For example, some Fabrics are sensitive to heat, while other fabrics are tracer-or are solvent-sensitive, so that particulate carriers or solvents are automatically excluded from mixing are. Other carriers, in turn, may be excluded because heat may be required to remove them to effect «The creation of a procedure that is generally used for

0 0 9 8 3 6/1884 ORIGINAL INSPECTED

Mixing of almost all particulate substances is suitable, is thus highly desirable. The method according to the invention has proven itself for a large " Range of substances proven useful that fall into each category.

Before forming a pulp, the particles are crushed so that they are normally smaller than one 200 mesh size. Are lesser amounts of a particulate matter with a much larger amount To mix a particulate substance evenly, the particles in question can be comminuted even more corresponding to a 3OO to 400 sieve size. Because the fabrics are usually ground in a very dry environment to keep out of the ambient moisture To avoid resulting short term or long term degradation problems, the finely divided particles become strong electrostatic Exposed to charging problems. This means that in the dry environment, the dry particles easily become one pick up electrostatic charge «, so that the following Mixing in a dry operation for all meanings and purposes are impractical,

After the respective substances have been comminuted to an appropriate size, a slurry is formed from these substances. If too little liquid is added to this pulp, the electrostatic charge problems are not completely overcome, which is why uniform mixing is not achieved. If, on the other hand, an excessive amount of liquid is added to the pulp, a layering effect occurs, whereby the particles or *. Particles are separated from each other rather than evenly mixed. Under Breiherstellung mixing the finely divided particles is thus understood with the liquid substance in suitable amounts. ', In such a way that the electrostatic ₉

Loading problems are avoided. Very little or no excess fluid is used in this, and besides occurs a separation or stratification of the corresponding Particles do not appear.

In general, X grams of the solid will be about 0.75 X t> is about 2 X milliliters of liquid carrier mixed. For many mixtures to be mixed together, an approximate mixture of X grams of solids has been found with X milliliters of carrier shown to be relatively useful. It should be noted, however, that the required for the slurry production The amount of fluid changes from time to time. It should also be noted that in the event that the mash additional If liquid is added, care should be taken to ensure that the solid particles are separated or stratified su prevent.

The liquid carrier which is added to the finely divided particulate substances to form the pulp expediently has a certain group of unique properties. First of all, the liquid carrier is neutral so that it does not affect the chemical reactivity of the final product. Furthermore, the carrier liquid should have a boiling point, that is, a boiling point above room temperature, so that ■ ciewähreric! successive fishings is not discharged in an undesirable manner. There are allowed η be apparent that a substance can be used with a low boiling point, wo.r. "ei β Kischvorrichrung suitably V / else during Mis'-Λ ·· ^ t ^". * 'R.': '* ^; hit is. The carrier should be on the other:) ■. .. > - .. -t.'. r.sufficiently high vapor pressure at a temperature ■ ;: ■ ■ * / .. ■■ the mixture not ., lf.ohtcilig influenced /oi;äj;.,-·,-· .j 'lit. · the transformer .. ^ :; it. such a high vapor pressure'.. .. Tt or n ^ear:.: gen Ternr ez- ^ vvi ' own «,

_{ofl | GINAL}

.that it can be readily removed from the mixture, such as by vacuum evaporation. The substance is expediently free of. Water, and furthermore, little or no residual proportion should remain after the discharge which could adversely affect the chemical properties of the batch. A particulate material which has been used with great success in the application of the “invention is the halogenated hydrocarbon 1, 1, 2-trichloro-1 !, 2, 2-trifluoroethane, which is also known under the trade name Freon TF (from EI Du Pond.de Nemours & Go. Inc.). Other typical liquid halogenated hydrocarbons contain: T ₁ "1, · 2, 2-tetrachloro-i -, 2-difluoroethane; 1, Ί, -2, 2-tetrafluoro-i, 2 dibromoethane; trichloromonofluoromethane; and azeotropes or mixtures of the above The liquid mixture obtained thereby does not affect the chemical reactivity of the mixed batch, and furthermore the mixing conditions are controlled in such a way that inedibility is prevented.

The slurry, once made, is mixed in a suitable device such as a ball mill. High-speed mixing device (Varying mixing device), etc. The mixing process is carried out for a sufficiently long period of time in order to obtain a homogeneous mixture. The actual Mischizeit changes from composition to composition, the size of the mixing amount produced in each case, and so on. On average, the mixing time is around one to six hours. When mixing very small mixing quantities at high speed (for example at a speed of 10,000 to 12,000 revolutions per minute), the mixing times can be reduced to three minutes or to minuifeB. Since in many cases heat-sensitive substances are mixed with one another, it is necessary in such cases to adjust the temperature

BADORIQINAL

to keep the mixture as close to room temperature as possible. This way it becomes a detrimental inedibility of the heat-sensitive substances avoided, so that the reactivity of the approach finally achieved can be regulated more appropriately.

If a ball mill is used as the mixing device, it is extremely useful to comminute the constituents of the mixture before making the slurry. Pre-comminution leads to a significant reduction in the mixing time L · within the ball mill. This also prevents particles of the porcelain balls from contaminating the end batch. In this way, an adverse effect on the optical properties of the prepared reagents is avoided if these reagents are used in an analysis process.

After the finely divided mixture in pulp form for a sufficiently long period of time in order to achieve a uniform Homogeneity is mixed together, the liquid carrier is removed, which is usually done by vacuum evaporation he follows. In the case of substances mixed with one another which are not sensitive to heat, the liquid from -P to be cooked. For most of the substances used in a reagent process, vacuum evaporation before loss chemical reactivity. The vacuum evaporation can be done in a simple manner that the now Container containing evenly mixed material with the top removed is introduced into a vacuum chamber. To The carrier is carried away by the evenly mixed material from the grinding material used during the mixing process separated. The uniform mixture can then take the form of a powdery material or, if desired, in tablet form be used.

009836/1884

The practical implementation, the invention explained in more detail. It should be noted that these examples are not limiting of the essence of the invention. These examples serve only to illustrate the invention.

example 1

According to this example, a reagent mixture is mixed and produced, which together with the mixture according to FIG Example 2 is used to determine glucose in body fluids.

The insert contains the following components with the respective specified proportions:.

Glucose oxidase 0.790 mg

Peroxidase 0.159 mg

Sodium phosphate, dibasic - "'5 * 520 mg sodium phosphate, monobasic 2.736 ^m 6

Potassium Chloride 9.795 mg

Polyethylene glycol 4000 1,000 m g

20,000 mg

Sufficient chemicals to make 20,000 tablets are then weighed in a dry room and placed in inserted into a dark brown ball mill container or other suitable grinding container containing porcelain balls. The container should be large enough to hold up to about $ 60 of its volume with the dry powder. A sufficient amount of abrasive in the form of Ooörs-HD balls is added to this powder or powder, so that the remaining $ 40 of the volume of the Are filled in the container. The size and amount of the abrasive can be varied if desired. Then will enough Freon TF carrier liquid to form a thick one

00 98 36/1884

Porridges added. In this example, about 400 milliliters of liquid are added to the substances. Between the Container and the closure cap is sufficiently thick Placed non-deformed polyethylene sheet, which avoids contamination by metal particles from the metal cap will. The slurry is then in a ball mill for about four hours at a speed of 90 revolutions each Minute kept moving. The cap is then removed and replaced with a cotton-free porous cover, which is attached with the help of a rubber band.

Ψ The container is then placed in a 30-degree position in a vacuum chamber that is equipped with a dry-ice-acetone hood. The vacuum is then slowly created at room temperature in order to prevent the Freon-TF carrier material from boiling over in a flash. The vacuum evaporation is continued for a sufficient period of time, typically two hours, to remove the excess carrier. The mixed powder is then passed through a 10-mesh screen to remove the abrasive. It should be apparent that the powder can also be dried in vacuo until a powder mixture is obtained which has less moisture content

P is Λ% . The powder is then stored in the dark and dry under nitrogen; If necessary, it can be shaped into reagent tablets which have the desired uniform mixture of the constituents.

An examination of the powder before the tablet production and of the tablets themselves shows that the substances in question are desirably uniformly mixed. It also shows that the substances are sufficiently reactive and that no residual proportion of the carrier material adversely affects any chemical properties of the material mixture influenced in such a way that the mixture in question would no longer be suitable for the intended purpose.

009836/1884

Example 2

The procedure of Example 1 is repeated to the following chromogenic composition to mix that together with the mixture according to Example 1 is suitable for the determination of glucose in body fluids.

o-dianisidine dihydrochloride 0.033 mg

Mannitol 14.00? mg

Polyethylene Glycol-4000 0.960 mg

15,000 mg

About 33 ° milliliters of Freon TF are sufficient for this approach to make the desired thick pulp.

Example 3

The procedure according to Example 1 is repeated to with the following chromogenic approach to obtain an even mixture. The approach in question is like that in the following example 4 indicated approach suitable in a total protein analysis according to the biuret method to be used. .

Copper II tartrate. . 0.663 mg

Sodium Tartrate, 1,779 mg

Potassium Chloride \ 10,558mg

Polyethylene Glycol-4000 1,000 mg

14,000 mg

Example 4

The procedure of Example 1 is repeated to the to mix the following alkalizing batch evenly, which together with the batch according to Example 3 in the total protein analysis according to the biuret process is suitable: lithiuiahyäroxid ■ 9,000 mg

Potassium chloride 4,000 mg

Polyethylene Glyco 1-4000 '. 1,000 mg

009836/1384

Example 5

The procedure of Example 1 is repeated to evenly mix the following batch, which together with those given below under Examples0i6 and 8 Approaches for the determination of uric acid in body fluids suitable is.

Copper sulfate 0.055 mg

Potassium Chloride 9.9 ^ 5 mg

10,000 mg

Example 6

The procedure according to Example 1 is repeated in order to mix the following alkalizing batch evenly, of the approaches given in Examples 5 and 7 for the determination of uric acid in body fluids suitable is:

Lithium hydroxide 0.0737 mg

Potassium Chloride 9.9263 mg

10.0000 mg

Example 7

The procedure of Example 1 is repeated in order to evenly mix the following chromogenic batch, which together with the approaches according to Examples 5 and 6 suitable for the determination of uric acid in body fluids:

2-Amino-2-methyl-1-propanol hydrochloride 4.228 mg, fteocuproin hydrochloride 0.143 mg

Potassium Chloride 5.029 mg

Polyäthylent.-lyi: ol-4000 0.600 mg

10,000 mg

009836/1884

Example 8

The procedure of Example 1 is repeated in order to evenly mix the following enzyme batch, which together with the approaches according to Examples 9 and 10 for the determination of blood urea nitrogen is suitable: Urease 0.01 mg

Ethylene diamine tetraacetic acid,

Disodium salt 0.10 mg

Mannitol 20.00 mg

20.11 mg

This example uses enough chemicals to make 1000 tablets along with 32 milliliters Preon TF mixed to form the pulp. The mixing process takes place in a ball mill for an hour and a half.

Example 9

The procedure of Example 1 is repeated to the following Mix evenly batch, together with the batches according to Examples 8 and 10 for the determination of Blood urea nitrogen is suitable:

Calcium Hypochlorite 0.028 mg

Lithium hydroxide: .r 0.375 mg

Sodium sulfate 0.875 mg

Mannitol 19,000 mg

20.278 mg

In this example, enough chemicals for 1000 tablets were mixed with 40 milliliters of Έτθοτϊ TF to form the pulp. The mixing process was carried out in the ball mill for one and a half hours.

009836/188 4

Example 10

The process of Example 1 is repeated to evenly mix the following batch, which together with the approaches according to Examples 8 and 9 for the determination of blood urea nitrogen is suitable:

Sodium salicylate 4,200O mg

Sodium nitroferricyanide 0.0125 mg

Mannitol 15.8000 mg

20.0125 mg

- In this example there are enough chemicals for 1000 tablets with 35 milliliters of Freon TF to form the pulp mixed. Mixing is done in a ball mill for an hour and a half.

Example 11

The process of Example 1 is repeated to the

Mix the following approach evenly, which is for the

Total protein determination using the biuret method is suitable is.

Trisodium phosphate 38.0 mg

W sodium tartrate 2.5 mg

Copper sulfate 0.5 mg

41.0 πκ;

In this example, enough chemicals for 50,000 tablets are mixed together with two liters of Freon TF to form the pulp. The mixing process is then carried out with cooling in liquid nitrogen for 20 minutes. The mixed powder is then dried for four hours in a vacuum at Zimmortomperatur lans and one hour at 100 ⁰ C.

009836 / 108A

The examples given above show the wide range of substances which can be uniformly mixed with one another with the aid of the process according to the invention. Biological substances such as the enzyme glucose oxidase, peroxidase and urease have been mixed together satisfactorily, as can be seen from Examples 1 and 8. Organic substances have been mixed satisfactorily, as proceeded from example 2, 7, "K) ₅ etc. Satisfactory mixtures of amino substances are also covered by the relevant examples. Mixtures of substances which fall into different classes are also with one another It should be noted, however, that the substances described here are to be regarded only as examples and that there is in fact no restriction on the substances which can be mixed with one another in the manner according to the invention.

The examples given above show in particular the equal mixing: small amounts of a first Substance with relatively large amounts of a second substance. For example, in Example 2 there are small amounts of orthodianisidine dihydrochloride with large amounts of mannitol in the proportion of one part ortho-ddanisidine to about. 420 parts of mannitol evenly been mixed. In Example 4, small amounts of copper sulfate are consistent with a large amount of potassium chloride been mixed, in the ratio of about one part ivuofersulfate to 180 parts potassium chloride. Since the Substances listed in the above examples are useful in analytical chemistry and especially in the Blood analysis, it is essential that the approaches in question are accurately and evenly mixed so that accurate and reliable analysis results can be achieved. Will e.g. insufficient chromogen in a particular chromogenic

009836/188 /,

20059S4

Approach disperr-ied, then the desired colorimetric Endpoint cannot be reached correctly during the analysis. As can be seen, this is unacceptable. In contrast, the same undesirable result, namely incorrect mixing, can be increased Lead to costs for the manufacturer who has to discard improperly presented reagents. This is it Finally, it is about costs that are passed on to the end user will. It should thus be seen that any method capable of producing a variety of particle F to mix shaped fabrics evenly and repeatedly

, is of great use and advantage, namely. direct or indirect for all concerned. The procedure according to the invention, as stated above, has brought about such results, although the relationship the constituents in the different approaches varied greatly.

The invention is admittedly above on the basis of specific embodiments has been explained. However, it should be understood that various changes have been made and Elements can be exchanged for other elements without deviating from the inventive concept. So can For example, other methods can be used to obtain the carrier material after uniformly mixing the items to be mixed together Discharge substances.

EAD OfilGsNAL 009836/188 4

Claims (8)

- ¹ 200596; · Patent a η s ρ rü che Experience for mixing particulate substances, characterized in that a slurry is produced from the finely divided particulate substances using a neutral carrier part, that the slurry is kept in motion until a homogeneous mixture of substances is obtained in it; is formed, and that the neutral carrier substance is then removed from the pulp without influencing the chemical reactivity or destroying the equilibrium of the substance mixture in such a way that in the substance mixture ultimately only a small amount or no residual substance of the carrier substance can be found kb 1 e ib t. 2. The method according to claim 1, characterized in that the particulate matter before ski manufacture be crushed. 3. Method according to Ansoruch 1 or 2, thereby ~ 3kenn draw:;, that as a neutral carrier an organic:;:? 3tc: f used will. 4. The method according to Ansoruch 3, characterized in that _; since an organic iitoff is used, its boiling point; is at least at room temperature and which has a sufficiently high vapor pressure at low temperatures for removal by vacuum evaporation. 5. The method according to any one of claims 1 to 4, characterized marked, da.C as a neutral carrier substance liquid halogenated hydrocarbon is used will. BAD ORlQfNAL 0 9 8 3 ^{6/188 /, L} 200596A 6. The method according to claim 5, characterized in that that as a neutral carrier 1,1 ·, 2-Jrichlor-1,2,2-trifluoromethane is used. 7. A method according to any one of claims 1 'to 6, characterized in that X to about gram of each other substances to be mixed from about 0.75 to 2 X i-Ii iilliliter neutral Trägerstofi' are added. ^ 8. The method according to claim 1, characterized in that * about X milliliters of neutral carrier substance at about X grams Solids are added. 9. The method according to any one of claims 1 to 8, characterized in that the particulate .Stoffe before the pulp production according to a sieve mesh size of 200 are comminuted. 10. The method according to any one of claims 1 to 9, characterized in that at least one particulate Before the pulp production, the substance is comminuted according to a sieve mesh size of 300 to 400. 11. The method according to any one of claims 1 to 10, characterized in that a small proportion of a first particulate matter uniformly with a main part at least one further particulate substance is mixed. 12. The method according to claim 11, characterized in that that v / enirrs.r al- 1 »of the first particulate matter: even with less than $ 99 at least one more partikelföi'ffiigoii Ji; o-! xs is provided. BATH ORIGINAL 0 9 8 3 6/188 / - 13- ■ method.according to one of claims 1 to 12, characterized characterized in that the neutral carrier material at - low temperature, made by vacuum evaporation is discharged from the pulp. ■ ·. Method test according to one of Claims 1 to. 12, thereby characterized in that the neutral carrier material by vacuum inoculation is removed from the slurry at room temperature. ■ 15 * method according to claim 1, characterized in that a very small amount of a first particulate Substance and a large amount of a second particulate Substance is severely comminuted that this ρarticulate substances with a corresponding amount a neutral organic carrier with formation a thick pulp are mixed together that this pulp "is mixed for a long enough time in such a way that the first particulate substance is in the second particle dispersed shaped substance, and that then the carrier without influencing the chemical reactivity of the mixed substances or destroying them the evenness of the mixture is discharged. 16. The method according to claim 15, characterized in that 'as a neutral ο organic carrier 1,1,2-Triciilor-i _t 2,2-trifluoromethane is used. Q 0 9 8 3 6/1 8 8 k ■ '. & AD ORlQlNAL