US3669358A - Mixing and dispensing apparatus - Google Patents

Mixing and dispensing apparatus Download PDF

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Publication number
US3669358A
US3669358A US96360A US3669358DA US3669358A US 3669358 A US3669358 A US 3669358A US 96360 A US96360 A US 96360A US 3669358D A US3669358D A US 3669358DA US 3669358 A US3669358 A US 3669358A
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Prior art keywords
inlet
pistons
liquid
openings
main cylinder
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Expired - Lifetime
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US96360A
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English (en)
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Jan Waldman
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/38—Diluting, dispersing or mixing samples
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S435/00—Chemistry: molecular biology and microbiology
    • Y10S435/975—Kit

Definitions

  • a mixing and dispensing apparatus comprises at least one horizontal main cylinder having a row of inlet openings at its top and a row of outlet openings at its bottom. Two pistons are displaceable in the cylinder in such manner that they may either be independently displaced, or simultaneously displaced at a constant distance from each other. At the end of each displacement, only one opening is uncovered. For preparing a dilution series, a separate inlet opening is provided for the liquid to be diluted and the other inlet openings are connected with a feed line for the diluent.
  • the invention relates to an apparatus for mixing liquids and for dispensing at least one mixture in a predetermined dose, and in particular to an apparatus of this kind for producing a series of consecutive dilutions of a given liquid.
  • liquid is intended hereinafter to cover both pure liquids and suspensions.
  • the known mixing and dispensing arrangements are generally complex and bulky and include valve systems of such kind that they are difiicult to handle and to clean and that they can not be satisfactorily sterilized.
  • the apparatus comprises at least one main cylinder provided with a plurality of inlet openings for liquids and with at least one outlet opening for a mixture, two pistons sealingly enclosed by said main cylinder, and a driving mechanism adapted to displace either of said pistons independently and to displace both pistons simultaneously at a constant distance from each other, in such manner that at most one of said openings is uncovered at the end of each displacement.
  • the main cylinder is formed as a horizontal tube having a row of longitudinally spaced inlet openings at its top and a row of correspondingly spaced outlet openings at its bottom, the outlet openings being staggered with respect to the inlet opening.
  • the apparatus may comprise a plurality of main cylinders arranged in parallel and means for interconnecting corresponding pistons in all main cylinders.
  • the apparatus is used to produce a series of consecutive dilutions of a given liquid the inlet openings and the outlet openings in the said rows are equally spaced and the inlet openings of said row are connected with a feed line for the diluent, while a separate inlet is provided for the liquid to be diluted.
  • This separate inlet may be arranged at different locations according to the reaction which is to be carried out with the dilution series.
  • the undiluted serum is used as a control liquid andin' this case, the inlet for the liquid to be diluted precedes the first inlet opening for the diluent at a distance corresponding with the distance between the inlet openings for the diluent.
  • the diluent is used as a control liquid and in this case, the separate inlet opening for the liquid to be diluted is placed between the first and the second inlet opening for the diluent.
  • nipples to the inlet and outlet openings which seal the openings and do not protrude into the interior of the main cylinder.
  • the cavity of the inlet nipples for the diluent is tapered in such manner that the opening discharging into the main cylinder is at the narrow end, whereas the cavity of the outlet nipples is substantially cylindrical.
  • the inner diameter of the inlet nipple for the liquid to be diluted should be of such size as to allow for the passage of the capillary tube of a Pasteur pipette.
  • the inner diameter and the wall thickness of all outlet nipples are preferably the same.
  • the pistons may be temporarily placed in a somewhat widened part of the main cylinders and to this end the main cylinder is preferably provided with flaring portions at both ends.
  • the main cylinder is preferably made of glass. This pistons, too, may be made of glass.
  • the driving mechanism which actuates thepistons in the main cylinder, should allow for a disconnection of the pistons
  • the driving mechanism should be adapted to move the pistons according to a specific schedule, which should be interchangeable in order to establish another dilution program.
  • FIG. 1 shows an elevation of a preferred embodiment of the invention, by means of which a dilution series of one-half, onequarter and one-fourth on, may be produced.
  • FIG. 2 shows a top view of this same apparatus on a somewhat smaller scale, in which details have been left out.
  • FIG. 3 shows on an enlarged scale a longitudinal cross-section of the main cylinder, in which only the portion comprising the mixing chamber has been represented.
  • FIG. 4 shows in outline the successive positions of the piston reference to rods in the main cylinder during the formation of the various dilutions for the case that the control sample consists of the liquid to be diluted.
  • FIG. 5 shows a corresponding diagram for the case that the control sample consists of the diluent.
  • the main cylinder is indicated by reference number 1; it is provided with flaring end portions 2, for purposes to be further elucidated hereinbelow.
  • the pistons 3 and 4 are located, which have been shown in FIG. 1 as solid rods.
  • the free ends of the pistons 3 and 4 are attached to the drive straps, 5 and 6 respectively.
  • the drive strap '6 is shown in shortened fashion; it extends far to the outside in reality, because the piston 4 is almost in its outermost position.
  • the piston 3, however, is almost completely pushed-in.
  • inlets At the top of the main cylinder 1, inlets have been provided, in which inlet nipples 7 have been fixed, which are in turn connected with tee-pieces 8, inserted in a feed line 9 for the diluent.
  • This feed line is connected with a supply vessel for the diluent (not shown).
  • outlets have been provided, in which outlet nipples 10 have been fixed.
  • Receptacles 11-22 are placed below each outlet nipple l0 and serve to receive the. control sample (vessel 11) and the series of dilutions (vessels 12-22).
  • an inlet nipple 23 for the liquid to be diluted is provided in a separate position at the top of the main cylinder, just past the first outlet (that is'to the right thereof in the drawing).
  • the opening of this nipple should be so wide that the capillary tube of a Pasteur pipette may pass through this nipple and reach the bottom of the main cylinder, if piston 3 uncovers its opening.
  • this inlet nipple is shown as a funnel and this is indeed a convenient embodiment thereof, because it allows to use this nipple for receiving the diluent, too, for instance during rinsing.
  • the feed line 9 is provided with a curved end portion for this purpose,
  • the apparatus may also be used for administration of the reagents to the dilution vessels.
  • the reagents are not diluted, so that the feed line for the diluent may be disconnected from the supply vessel for the diluent and connected, for instance, with the inlet nipple for the liquid to be diluted. This inlet nipple is then used for receiving and distributing the reagents.
  • the main cylinder 1 is incorporated in a frame 24 with a base 25, in which the driving mechanism of the apparatus is accommodated (not shown). Shown in the drawing are only the conveying gear-wheels 26 and 27, which may be induced in a known manner to mesh with gear racks 28 and 29, respectively, provided at the bottom side of the drive straps 6 and 5.
  • the actuation of the piston may also be effected by any other disengageable means, for instance, by belts or friction rollers.
  • FIG. 2 shows the machine from above, omitting details of the liquid inlets and outlets for claritys sake.
  • FIG. 3 serves to explain the actual mixing process and shows an enlarged longitudinal section of the main cylinder, representing only that part thereof in which the mixing chamber is situated at that moment.
  • the pistons are shown in the positions in which the mixing chamber has just been filled with liquid coming from the inlet nipple 7; this liquid has obtained a higher speed by virtue of the tapered shape of the nipple 7, which promotes the mixing in the mixing chamber.
  • a small stirring magnet 30, incorporated in a synthetic material such as Per- Ion may be introduced into the mixing chamber through the separate inlet nipple 23 for the liquid to be diluted, which nipple will generally have a larger inner diameter than the other inlet nipples; the stirring magnet is brought into rotation in known manner by means of a rotating magnetic field.
  • nipples In order to prevent a penetration of the nipples into the interior of the main cylinder, it is advantageous to provide the nipples at the outside in the proper place with a collar 31, which prevents insertion of the nipple beyond a certain level.
  • FIG. 4 explains the operation of the apparatus while making a dilution series of 1:2, 1:4, 1:8 and so on, fora complement binding reaction, that is for a reaction in which the control sample consists of the undiluted serum.
  • FIG. 4a the starting position of the pistons in the main cylinder is indicated.
  • the piston 4 is situated with its end face just in front of the inlet nipple for the liquid to be diluted
  • piston 3 is situated with its end face just in front of the first outlet opening.
  • the distance between both pistons is such that a space is formed having twice the volume which should be squeezed out into the control vessel and into allvdilution vessels. This distance is 2a.
  • the space between the pistons is now filled through the separate inlet nipple 23 and by means of a Pasteur pipette (of course by hand) with the liquid to be diluted.
  • the pipette needs no calibration and an adjustment of the pipette volume by flowing off surplus liquid is also unnecessary, because the apparatus itself defines the liquid volume comprised by the mixing chamber.
  • the pipette needs be used only once.
  • both pistons are first simultaneously shifted over a distance a in the direction of the piston 3 (to the right), while maintaining the distance 2a between them.
  • the situation then arising is illustrated in FIG. 4b.
  • the mixingchamber, filled with a double, volume of the liquid to be diluted, is now in communication with the first outlet nipple 10, whereas the inlet nipples 23 and 7 are closed.
  • the liquid is prevented from flowing out through the outlet nipple by the atmospheric pressure.
  • the transitions from FIG. 4g to FIG. 4h, from FIG. 4h to FIG. 4k, from FIG. 4k to FIG. 41 and from FIG. 41 to FIG. 4m correspond, respectively, with the transitions from FIG. 40 to FIG. 4d, from FIG. 4d to FIG. 4e, from FIG. 4e to FIG. 4f and from FIG. 4f to FIG. 4g. Any further steps are performed in an analogous manner. 7
  • FIG. 5 Another embodiment of the main cylinder is represented in FIG. 5, also showing the production of a dilution series of 1:2, 1:4, 1:8 and so on, but with the control sample consisting of the diluent, as is usual, for instance, in agglutination reactions.
  • the piston are in starting positions suitable for the production of the control sample, which now consists of the pure diluent.
  • the pistons engage each other with their end faces just in front of the first inlet nipple 7.
  • both pistons are moved in the main cylinder over a distance d while maintaining their mutual distance a, d
  • the liquid to be diluted the serum
  • one or more reagents are added to the serum dilutions in all serological reactions.
  • an amount of reagent is added which is equal to the volume of the serum dilution itself.
  • the same apparatus may be used. After rinsing for removing all serum residues, the feed line 9 is connected with the inlet nipple 23 and the reagent is fed through the feed line.
  • the apparatus may operate according to the same program as before to deliver the same volume of reagent to each receptable.
  • the volume of the administered reagent is equal to the volume of the serum dilution already present in the receptacle.
  • the rinsing and deaerating should be repeated, of course. During this rinsing and deaerating the receptacles should not be present, so that they should be easily removable.
  • the main cylinders with their pistons, nipples, feed lines, and so on should be thoroughly cleaned, of course, and for applications in the bacterological field, they should also be sterilized.
  • the main cylinders comprise the flaring end portions indicated by reference number 2 in FIG. 1.
  • both pistons are extracted so far from the main cylinders that their end faces lie within the flaring end portions.
  • a possible irregular expansion of the pistons or of the main cylinder cannot lead to breakage.
  • the inlet nipples should be all filled with the diluent and deaerated. This may be done with the pistons in the extended as well as in the pushed-in positions. Deaeration with pushed-in pistons (for example, by knocking) provides the advantage that the outlet nipples stay free from liquid.
  • the main cylinders and the pistons are preferably made from glass, whereas the nipples, connections and so on are mainly made from a heat resisting synthetic resin, which may withstand at least a temperature of 120 Centigrade.
  • the detached frame is mounted again on the driving mechanism and the receptacles are placed on the bed plate positioned below the main cylinders.
  • These receptacles may be reaction tubes, placed in a specially designed rack, or in holes of a plastic plate fitting to the bed plate.
  • the bed plate In order to avoid contamination of the dilutions, it is desirable to press the bed plate upwards as far as possible after insertion of the receptacles, so that the bed plate should be movable, preferably in a vertical direction.
  • the apparatus depicted hereinabove is especially advantageous in performing serological reactions, bacterial sensitivity determinations, detenninations of antibiotic blood levels and determinations of bacteria, in which a series of culture media are filled and innoculated. All serological reactions in which the concentration (titre) of antibodies should be detemiined in a patients serum may be performed with the apparatus according to the invention. Mention may be made of the Wassermann reaction, the Waller-Rose test and Widal's agglutination reactions. in these serological reactions, which are to be performed very frequently, itwas up till now impracticable to carry out all reactions in a large series of dilutions. Usually only two or three dilutions were tested.
  • the determination of the antibiotics content of the blood (the blood level) according to the Rammelkamp method is another example of a method which involves so much labor, that it is only performed out of extreme necessity.
  • the dilution apparatus according to the invention it is possible to carry out the determination as a routine test, thus providing an efficient method for controlling the effect of antibiotics administration. Especially with. patients with a bad kidney function, who have difficulty in excreting the antibiotic, such a control is important.
  • the determination of bacteria count in urine, ascites liquid and other liquids, in which use is made of dilution series, may be carried out with the apparatus according to theinvention. In these cases, however, the receptacles are replaced by a large plate with a solid culture medium.
  • the bacterium to be determined is inoculated on a series of mutually different culture media.
  • the apparatus according to the invention may be used for the production of the series of culture media as well as for the inoculation thereof in the following manner.
  • Each main cylinder of the apparatus receives through feed line 9 (and inlet nipple 23 connected therewith) one of the different culture media and dispenses a constant volume of this specific culture medium into the corresponding receptacles. This gives rise to a number of rows, of which each row consists of the same culture medium, while all rows are mutually different.
  • the rack with receptacles is turned through an angle of thus placing the main cylindersover and above a number of identical rows of mutually different culture media.
  • the apparatus is used, in the same manner as for dispensing the culture media, for dispensing equal volumes of the bacterium strains to be determined.
  • the apparatus according to the invention has many advantages. First of all, a substantial saving of time is obtained and less man-power is needed. In the use of the pipette, no measurement errors can be made. if there is a deviation in the apparatus, this deviation will automatically always be the same. Thus a better possibility is obtained for comparing two samples of the same patient, taken at different times. The rinsing of large amounts of pipettes, which was formerly necessary, and which involved a lot of breakage,
  • the apparatus may be easily sterilized in its entirety.
  • the apparatus according to the invention Secondly it is made possible by the apparatus according to the invention to carry out determinations in a routine manner which could not or only exceptionally be performed before. Moreover, due to the rapid operation of the apparatus, the first made dilutions need not stand for a too long time before the subsequent reagents are added. This is especially important for large numbers of tests, as necessary, for instance, for the Wassermann reaction.
  • the dilutions are produced with the apparatus according to the invention in a theoretically more correct manner than was hitherto usual in view of practical considerations.
  • the diluent is added to the serum, thus substantially diminishing the chances of hydrolysis of the antibodies.
  • Apparatus for mixing liquids and for dispensing at least one mixture in a predetermined dose comprising at least one main cylinder provided with a plurality of inlet openings for liquids and at least one outlet opening for a mixture, two pistons sealingly enclosed by said main cylinder, and a drive mechanism adapted to displace either of said pistons independently and to displace both pistons simultaneously at a constant distance from each other, in such manner that at most one of said openings is uncovered at the end of each displacement.
  • main cylinder is formed as a horizontal tube with a row of longitudinally spaced inlet openings at its top and a row of correspondingly spaced outlet openings at its bottom, the outlet openings being staggered with respect to the inlet openings.
  • Apparatus as claimed in claim 2 for producing a series of consecutive dilutions of a given liquid, further comprising a feed line for the diluent, wherein said inlet and outlet openings are equally spaced and said inlet openings are connected with said feed line, while a separate inlet opening is provided for the liquid to be diluted.
  • each independent displacement of a piston extends through the distance required to admit or to dispense, respectively, a required liquid volume, and each simultaneous displacement of both pistons extends through the distance required to render a subsequent admission or dispensing possible.
  • Apparatus as claimed in claim 3 further comprising a plurality of nipples, each applied to one of the inlet and outlet openings sealing said openings and spaced from the interior of said main cylinder.
  • Apparatus as claimed in claim 1 comprising a plurality of main cylinders arranged in parallel, and means for interconnecting corresponding pistons in all said main cylinders.

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  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Accessories For Mixers (AREA)
US96360A 1969-12-10 1970-12-09 Mixing and dispensing apparatus Expired - Lifetime US3669358A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
NLAANVRAGE6918495,A NL169519C (nl) 1969-12-10 1969-12-10 Inrichting voor het bereiden van toenemende verdunningen van een vloeistof en/of emulsie met een andere vloeistof en/of emulsie, met een doseerpomp.

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US3669358A true US3669358A (en) 1972-06-13

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US96360A Expired - Lifetime US3669358A (en) 1969-12-10 1970-12-09 Mixing and dispensing apparatus

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US (1) US3669358A (de)
CH (1) CH521784A (de)
DE (1) DE2060559C3 (de)
FR (1) FR2073193A5 (de)
GB (1) GB1312364A (de)
NL (1) NL169519C (de)
SE (1) SE356222B (de)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3972778A (en) * 1972-11-17 1976-08-03 William Eric Cunningham Apparatus for determining the concentration of microorganisms
US4416596A (en) * 1981-04-09 1983-11-22 Lichtenstein Eric Stefan Fluid-transfer system and method
US4635829A (en) * 1985-05-30 1987-01-13 Brittingham Jr Louis W Measured volume dispenser
US20050062574A1 (en) * 2001-11-20 2005-03-24 Fritz Frey Circuit arrangement for the reliable switching of electrial circuits
US20060118580A1 (en) * 2003-06-06 2006-06-08 Alan Spencer Dispensing apparatus and a dispensing nozzle for use therewith

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2915248C3 (de) * 1979-04-14 1982-01-14 Gise, Frhr. von, Hardo, Dr.med., 7400 Tübingen Einrichtung zum automatischen wahlweisen u. exakten Behandeln von Präparaten

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3221948A (en) * 1962-09-26 1965-12-07 Ernest S Kalist Metering and injection device
US3285669A (en) * 1964-05-20 1966-11-15 James D A Clark Feeding and extracting apparatus and method

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3221948A (en) * 1962-09-26 1965-12-07 Ernest S Kalist Metering and injection device
US3285669A (en) * 1964-05-20 1966-11-15 James D A Clark Feeding and extracting apparatus and method

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3972778A (en) * 1972-11-17 1976-08-03 William Eric Cunningham Apparatus for determining the concentration of microorganisms
US4416596A (en) * 1981-04-09 1983-11-22 Lichtenstein Eric Stefan Fluid-transfer system and method
US4635829A (en) * 1985-05-30 1987-01-13 Brittingham Jr Louis W Measured volume dispenser
US20050062574A1 (en) * 2001-11-20 2005-03-24 Fritz Frey Circuit arrangement for the reliable switching of electrial circuits
US20060118580A1 (en) * 2003-06-06 2006-06-08 Alan Spencer Dispensing apparatus and a dispensing nozzle for use therewith

Also Published As

Publication number Publication date
NL169519B (nl) 1982-02-16
GB1312364A (en) 1973-04-04
NL169519C (nl) 1982-07-16
SE356222B (de) 1973-05-21
DE2060559A1 (de) 1971-06-16
NL6918495A (de) 1971-06-14
FR2073193A5 (fr) 1971-09-24
DE2060559B2 (de) 1975-01-16
CH521784A (de) 1972-04-30
DE2060559C3 (de) 1975-09-04

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