US 3421858 A
Description (OCR text may contain errors)
Filed Dec. 7. 1965 Fill/l DILUENT SUPPLY INVENTOR.
a. N I Y U QQ F. m @w E A 5 0% United States Patent 9 Claims ABSTRACT OF THE DISCLOSURE Fluid dilutions are made using coaxially disposed sample and diluent cylinders separated by a check valve permitting flow from the diluent to the sample cylinder. The sample chamber has a sample dispensing piston of constant cross-sectional area which extends from the sample cylinder through the diluent cylinder and is connected for reciprocatory motion to the diluent piston. The diluent chamber has a constant cross-sectional area. Reciprocation of the diluent piston successively draws a volume of sample into a sample dispensing tube connected to the sample cylinder and a volume of diluent into the diluent cylinder and then dispenses the sample and diluent in a volume ratio determined by the ratio of the cross-sectional area of the diluent cylinder to the sample piston. This ratio is independent of the stroke of the pistons.
This invention relates to the processing of laboratory samples and, more particularly, to apparatus for the apportionment and dilution of fluid samples to a dilution ratio that is highly accurate and repeatable.
In many analytical procedures, and especially those employed in biochemical, physiological and medical laboratories, a standard or predetermined volume of the sample is taken from a specimen, e.g., blood, plasma, urine or other fluid obtained from a patient or biological source. This standard volume is diluted or admixed with a reagent or diluent to provide an analytical sample. Customarily these operations are performed manually and are time consuming and tedious, especially when numerous similar specimens are being processed or when large dilution ratios are required. Moreover, the opport-unity for error is considerable and particularly so unless extreme care is taken and skill employed. Similar requirements and problems occur in other fields such as medicinal dose preparation and the like.
One apparatus which has been devised for mixing a reagent or diluent with a sample in predetermined volumetric ratios is described in US. Patent 3,012,863, issued to Thomas V. Feichtmeir on Dec. 12, 1961. While the Feichtmeir apparatus is satisfactory, in many respects it is subject to certain inaccuracies. This is because the precise volume of sample and a precise volume of diluent or reagent must be separately and carefully measured if the dilution ratio is to be obtained with the desired degree of accuracy. These errors are particularly pronounced when the dilution ratios desired are relatively large since it is difficult to accurately measure a volume of the smaller volume component of the mixture. Feichtmeir attempts to solve this problem and remove human error by the use of a syringe having a known volume and precisely controlling the stroke of the syringes plunger. Unfortunately, the accuracy of the dilution is easily disturbed since relative small changes in the plunger stroke introduces relatively large changes in the volume of the fluid drawn into or expelled from the syringe. Such changes cause errors in the dilution ratio.
It is, therefore, an objeect of this invention to obviate many of the disadvantages of prior art sample preparation systems.
3,421,858 Patented Jan. 14, 1969 Another object of this invention is to mix a sample and a reagent in a predetermined volumetric ratio with a high degree of accuracy.
Still another object of this invention is to provide an improved apparatus for apportioning a sample and a reagent which apparatus reduces the number of variables affecting the apportionment.
In accordance with a preferred embodiment of this invention first and second chambers are positioned along a common axis. A diluent piston provided with a reciprocating motion within the second chamber varies the volume of diluent in the second chamber. A sample or displacement piston having a constant cross-sectional area is axially mounted on the diluent piston and extends through the second chamber and into the first chamber. Reciprocation of the diluent piston causes the displacement piston to displace a volume in the first chamber determined by the cross-sectional area and stroke of the displacement piston.
By constructing the second chamber to have a constant cross-sectional area along the axis of piston reciprocation, the reciprocation of the diluent piston successively draws a volume of sample into the first chamber and a volume of diluent into the second chamber and then discharges the sample and diluent in a ratio determined by the cross-sectional areas of the second chamber and the displacement piston through the first chamber. The dilution ratio is dependent only upon the ratio between the cross-sectional areas and is completely independent of the length of the stroke of the piston as in prior art devices.
The novel features that are considered characteristic of this invention are set forth with particularity in the appended claims. The invention, itself, however, both as to its organization and method of operation, as well as additional objects and advantages thereof, will best be understood from the following description when read in connection with the accompanying drawings, in which:
FIGURE 1 is a cross-sectional representation of an apportioning apparatus constructed in accordance with this invention; and
FIGURE 2 is an exploded view of a portion of the dilution apparatus illustrated in FIG. 1.
In describing the apportioning apparatus of this invention reference may be made to both FIGS. 1 and 2. It may be seen with particular reference to FIG. 1 there is provided a drive housing 10 in the lower portion of which is mounted a bidirectional or reciprocating linear actuator 12 of conventional design. The actuator 12 may be, for example, a solenoid, a motor, or any other suitable prime mover. When actuated in a first direction, the actuator 12 drives a diluent piston member 14 upwardly in the drawing within a chamber illustrated as a cylinder 16. Peripheral grooves are formed in the upper periphery of the diluent piston 14 to retain O ring 20. This 0 ring 20 maintains a sliding seal between the inner wall of the cylinder 16 and the dileun-t piston 14. The upper portion of the housing 10 is provided with an inner flanged portion 22 so as to provide a lower limit stop for the travel of the piston 14. The lower portion (in the drawing) of the piston 14 is of reduced diameter so as to provide a stepped portion 24 which engages the flange 22. This lower limit stop is not critical and need not be constructed with precision.
The cylinder 16 may be screwingly engaged by threads formed in the upper, inner peripheral portion of the housing 10. A longitudinal slot 26 formed in the side of the housing 10 permits a conventional tubing connector 28 to be inserted radially and screwingly engaged by threads formed in the side wall of the piston 14. A bushing 29 about the tubing connector may be used to reduce fric- 3 tion with the slot 26. An axial bore 30 in the piston 14 provides a conduit through the center of the piston from the tubing connector 28 up through a spring loaded diluent valve 32 into a valve chamber 34 formed by a counter-bored region within the piston 14.
A sample piston assembly 36 includes a disc-shaped member 38 positioned in a second counter-bored region 40 within the piston 14. The disc 38 itself rests on the step formed between the two counter-bored regions 34 and 40 and is fixed in position by a retainer ring 74 which engages a groove 75 in the inner wall of the second counter'bored region 40. The discshaped member 38 mounts an axially disposed displacement or sample piston 37 which may be formed from a small piece of wire or rod stock. Axial holes 42 formed in the disc 38 permit the flow of diluent fluid from the chamber 34 into a larger chamber 44 enclosed by a cylinder head 46 which seals the upper portion of the cylinder by means of an O ring 48 peripherally disposed in a peripheral groove 49 in the cylinder head 46.
A nozzle assembly 50 is formed by a casting or mold to have a tapered interior chamber with a continuously decreasing diameter and a flanged base portion adapted to sealingly engage the cylinder head 46 by means of an O ring 52. A collar 60, adapted to screwingly engage the upper peripheral portion of the cylinder 16, retains the cylinder head 46 and the nozzle 50 in position.
The sample piston 37 is adapted to pass through a central axial hole of larger diameter than the piston 37 in the cylinder head 46 and thence through a central axial hole in a sample valve 62. The sample valve 62 may be in the form of a silicon rubber disc providing a tight but sliding fit about the sample piston 36. This prevents leakage of fluid from the chamber in nozzle 50 about the piston 36 through the sample valve 62 into the larger diluent chamber 44. Separate valve springs 64 retain each of the valves 62 and 32 normally in a closed position to permit only unidirectional fluid flow from the tubing connector into the diluent chamber 44 and thence to the chamber in nozzle 50. A pipette-shaped spout 66 is positioned at the end of the nozzle 50 by means of end cap 68. The spout 66 which may be formed of glass, metal or other suitable material is tapered to have a decreasing interior diameter down to preferably that approaching capillary size to help keep the system purged with fluid at all times and of sufficient length to hold the complete volume of sample within its interior diameter as will be described hereinafter. The tubing connector 28 may be connected to a bottle of diluent supply 70, by means of a tubing 72 which fits over the end of the tubing connector 28. The valves may all be formed of silicon rubber or other suitable resilient material. The remaining parts of the diluter assembly are formed preferably of stainless steel or other noncorrosive material.
In operation, the solenoid 12 is actuated several times initially so as to drive the diluent and sample pistons 14 and 37, respectively, up and down within the cylinder 16. This primes the valve chamber 34, the cylinder chamber 44, the nozzle 50 and the spout 66. With the priming, diluent from the diluent supply 70 passes through the tubing 72, tubing connector 28, the conduit formed by axial bore 30, the diluent valve 32, into the cylinder chamber 44 and thence upwardly in the annular passageway in the cylinder head 46 about the sample piston 36 through the sample valve 62 into the nozzle 50' and the spout 66 such that the entire system is filled with a diluent. A container of the specimen is placed so that the end of spout 66 dips into the specimen itself. The actuator 12 is energized as by a switch (not shown) to draw the pistons 14 annd 37 in a first direction, downwardly in the drawing. This action of the sample piston 37 draws an amount of specimen into the tip of the spout 66. The particular amount is dependent upon the volume displaced within the nozzle 50 by the sample piston. This volume is dependent on the cross-sectional area of the sample piston 37 and the length of its downward stroke. The sample valve 62 does not permit any sample fluid or diluent fluid to flow from the nozzle 50 back into the chamber 44. Its sealing action is enhanced by the downward motion of the sample piston 37. Preferably, only the lower portion or tip of the spout 66 is filled with sample fluid. At the same time, the downward movement of the diluent piston 14 increases the volume of the chamber 44 thereby drawing diluent up through the valve 32 from the diluent supply 70 to fill the cylindrical chamber 44. The volume of diluent drawn into the chamber 44 is determined by the difference in crosssectional area of the cylinder 16 and the sample piston 37 multiplied by the length of the diluent piston stroke.
The actuator 12 is now again energized to discharge the diluent and sample throught the spout, by moving the pistons 14 and 37 upwardly in the drawing by the same distance as the downward stroke. The diluent valve 32 closes with the fluid pressure acting with the force of spring 64 such that the fluid in the chamber 44 is forced upwardly through sample valve 62 (which opens under the force of fluid pressure acting against its spring 64), nozzle 50, and spout 66 thereby flushing the sample in the tip of nozzle 50 out into a sample container which has been placed at the end of the spout 66. The total volume of diluent and sample discharged (which may be termed the sample product) is the volume in the chamber 44 mentioned above plus the volume displaced in the nozzle 50 by the sample piston 37.
Little attempt is made to accurately control the length of the piston stroke so as to achieve particular volumetric measurements. Rather, as long as the length of the piston stroke in each direction is the same, an accurate repeatable ratio of diluent to sample is obtained. The determining factor for the dilution ratio is the ratio of the cross-sectional area of the cylinder 16 to that of the sample piston 37. Once this area ratio is accurately determined, so long as the upward and downward stroke of the pistons are maintained the same, the ratio will be accurate and repeatable sample after sample even though the precise volume is not.
Diluent dilution ratios may be obtained simply by selecting different cross-sectional areas for the sample piston 37. The sample piston assembly may be easily replaced by removing the cylinder head 46 and the retainer ring 74. The cylinder head 46 is easily removed by unscrewing the collar 60 and lifting off the nozzle 50.
It will be obvious that various modifications may be made in the apparatus and in the manner of operating it. It is intended to cover such modifications and changes as would occur to those skilled in the art, as far as the following claims permit and as far as consistent with the state of the prior art.
What is claimed is:
1. Apparatus for the apportionment and dilution of a fluid specimen by a diluent to provide a sample product comprising, in combination:
a first chamber adapted to be in communication with said specimen,
a second chamber having an axis, a substantially constant cross-sectional area along said axis, and adapted to be in communication with said diluent,
a first piston member disposed in and adapted to reciprocate on the axis of said second chamber,
a second piston member of substantially constant crosssectional area fixedly mounted on said first piston member and extending through said second chamher into said first chamber,
first valve means for permitting the unidirectional flow of fluid from said second chamber into said first chamber, and
means to reciprocally displace said first piston member within said second chamber equal distances along said axis, thereby to vary the volume of both of said chambers in the same sense and in a predetermined volumetric ratio that is substantially independent of the displacement of said first piston member along said axis.
2. The apparatus set forth in claim 1 which also includes a second valve means for permitting the unidirectional flow of said diluent into said second chamber.
3. The apparatus set forth in claim 1 wherein said second piston member has a cross-sectional area less than the cross-sectional area of said first piston member and which combination includes a spout in communication with said first chamber, said spout being of sufiicient length to hold the complete volume of sample within its interior volume.
4. The apparatus set forth in claim 1 wherein the ratio of sample plus diluent to sample is proportional to the ratio of the cross-sectional area of said second chamber to the cross-sectional area of said second piston member and is substantially independent of the displacement of said first piston member along said axis.
5. The apparatus set forth in claim 1 wherein said first valve means for permitting the unidirectional flow of fiuid from said second chamber into said first chamber is a rubber disc with a central axial hole which seals against said second piston member and a first face to provide sealing between said first and second chambers.
6. The apparatus set forth in claim 1 wherein the ratio of diluent to sample is proportional to the ratio of the cross-sectional area of said second chamber minus the cross-sectional area of said second piston member to the cross-sectional area of said second piston member.
7. The apparatus set forth in claim 1 wherein said second chamber is a hollow cylinder having inner walls and a predetermined inner diameter, said first piston member being adapted to sealingly engage the inner walls of said cylinder.
8. The apparatus set forth in claim 7 wherein said second piston member is cylindrical and has a substantially constant diameter.
9. The apparatus set forth in claim 8 wherein the ratio of sample plus diluent to sample in the sample product is proportional to the square of the quotient of the diameter of said second chamber divided by the diameter of said second member.
References Cited UNITED STATES PATENTS 3,012,863 12/1961 Feichtmeir 23-253 3,192,969 7/1965 Baruch et a1. 23259 XR 3,193,359 7/1965 Baruch et al. 23-253 XR 3,197,285 7/1965 Rosen 23253 MORRIS O. WOLK, Primary Examiner. R. E. SERWIN, Assistant Examiner.
US. Cl. X.R.