Apparatus For The Precision Metering Of Fluids

Abstract

There is disclosed a first capillary conduit having a minute aperture therein, the aperture dividing the first conduit into a separate and a common section, there being a first fluid conducting path formed through the separate and common sections. A second capillary conduit has one end thereof intersecting the first conduit and mating with the minute aperture to form a second fluid conducting path through the second conduit and the common section of the first conduit. The minute aperture forms a first precise interface between the first fluid path and the second conduit. The capillary cross-section of the first conduit separate section adjacent the minute aperture forms a second precise interface between the second fluid conducting path and the separate section, whereby fluid can traverse the first fluid path substantially free from contamination from fluids adjacent the first precise interface and fluids can traverse the second path substantially free from contamination from fluid adjacent the second precise interface.

Description

The present invention relates to the precision aspiration and dispersion of fluid and more particularly to sample aspirating and dispensing systems for chemical analysis of blood serum.

In the field of chemical analysis of blood serum, it has been the general practice to employ automated and semiautomated equipment to perform the desired chemical and analytical tests upon blood serum. These automated systems duplicate actual test tube procedures. Each test is treated as a discrete entity and must be free from cross-contamination or carry-over between the various chemical tests performed. In these automated systems, samples generally are placed in small cups that are positioned on a movable sample table. In order to perform the desired test, a predetermined quantity of sample must be dispensed into an individual reaction tube. These reaction tubes are advanced by a conveyor system through a series of reaction stations where reagents are added, as required, and reactions proceed under precise temperature control. The contents of each reaction tube are sequentially scanned colorimetrically to provide a measurement of concentration or reaction activity. An essential and critical part of the automated blood chemistry system is the serum aspirating and dispensing apparatus. This apparatus aspirates the serum sample from the sample cup and dispenses it into the reaction tubes. These functions have been accomplished by a hydraulic system which gives a high degree of precision and accuracy. Initially, a serum arm moves over the sample table and an aspiration-dispensing needle travels to a pick-up position. It has been the practice to introduce an air-interface between the hydraulic fluid which is generally de-ionized water and the serum aspirated into the apparatus. The air interface prevents any mixing between the de-ionized water and the serum. In one prior art system, after the required amount of sample is aspirated, a delivery is made back into the sample cup to assure that all test deliveries will be correct. The arm then moves over the reaction tube and programmed deliveries of predetermined amounts of serum are deposited into each individual reaction tube. When sample dispensing into the reaction tube is completed, the needle is washed and the system is flushed with the de-ionized water. In a typical system, the amount of sample aspirated is about 0.25 milliliters, or 250 lambda, plus a volume for each test to be performed, which averages about 0.05 milliliters or 50 lambda. Therefore, the total sample volume required ranges from 0.3 milliliters for one test and 1.05 milliliters for 16 tests. Although the serum sample aspirating and dispensing devices have served the purpose, they have not proved entirely satisfactory under all conditions of service for the reason that considerable difficulty has been experienced in precisely controlling the aspirated and dispensed amounts of serum to accuracies approaching 1/2 lambda. These problems have resulted from the volume inaccuracies produced by the cushioning effect of the air interface between the de-ionized water hydraulic fluid and the serum and in the formation of surface tension drops of serum at the end of the aspirating and dispensing needle, which can be of a size having a volume of 10 lambda.

Those concerned with the development of serum aspirating and dispensing systems have long recognized the need for aspirating dispensing apparatus which accurately controls serum volumes approaching 1/2 lambda in precision and accuracy. The present invention fulfills this need.

One of the most critical problems confronting designers of apparatus for the precision volume dispensing of blood serums has been the prevention of contamination and uncontrolled dilution of the serum. The present invention overcomes this problem.

The general purpose of this invention is to provide a precision fluid metering device which embraces all the advantages of similarity employed fluid aspirators and dispensers and possesses none of the aforedescribed disadvantages. To obtain this, the present invention contemplates a unique combination of a silicone oil hydraulic fluid and an intersecting capillary conduit arrangement in the fluid pick-up and dispensing needle whereby inaccuracies of surface tension drops and fluid interface mixing are avoided.

An object of the present invention is the provision of the precision aspiration and dispersion of fluid free from inaccuracies of surface tension drops.

Another object is to provide precision hydraulic aspiration and dispersion of fluids wherein the hydraulic fluid does not mix or contaminate the fluids aspirated and dispersed.

A further object of the invention is the provision of a dual hydraulic fluid aspiration and dispersion system whereby a test fluid may be aspirated and dispersed by one hydraulic fluid which does not mix or contaminate the test fluid and whereby the test fluid may be dispersed by the other hydraulic fluid to avoid inaccuracies of surface tension drops of the test fluid.

Still another object is to provide a first precise interface between fluid flowing in a first fluid path and fluid in a second fluid path and a second precise interface between fluid flowing in a second fluid path and fluid in the first fluid path.

Another object of the present invention is the provision of two separate fluid paths having a common section with a first precise interface between fluid traversing one fluid path and fluid in the other fluid path and a second precise interface between fluid in the one fluid path and fluid traversing the other fluid path.

Other objects and many of the intended advantages of this invention will be readily appreciated as the same becomes better understood by reference to the following detailed description when considered in connection with the accompanying drawing in which like reference numerals designate like parts throughout the figures thereof and wherein:

FIG. 1 illustrates a partly mechanical and partly block diagram of a preferred system embodiment of the invention;

FIG. 2 illustrates a cross-sectional view of the fluid pick-up and dispensing needle probe of FIG. 1;

FIGS. 3(a), (b), (c), (d), and (e) illustrate various fluid positions in the pick-up and dispensing probe encountered during the operation of the fluid aspiration and dispersion system of FIG. 1; and

FIG. 4 illustrates a pictorial view of the pick-up probe embodiment of the invention.

Referring now to the drawings, there is shown in FIG. 1 (which illustrates a preferred embodiment) a probe having common capillary conduit sections 7 and separate capillary conduit section 9 which together form a first capillary conduit and a first fluid path. A second capillary conduit 11 intersects the first capillary conduit at a minute aperature therein to provide a second fluid path through common section 7 and second capillary conduit 11. Fluid conduit 13 connects separate section 9 of the first capillary conduit to diluent syringe 15. Fluid conduit 17 connects second capillary conduit 11 to silicone oil syringe 19. Diluent syringe 15 has fluid port or opening 21 in the side thereof connected to diluent reservoir syringe 23. Piston 25 is located within diluent syringe 15 and piston 27 is located within diluent reservoir syringe 23. The interior volume of diluent reservoir syringe 23 is designated as volume 28. Shaft 29 connects piston 25 to bracket 31 which in turn has a threaded opening therein into which screw 33 is engaged to form a screw-drive mechanism. Screw 33 in turn is connected to shaft 37 of digital stepping motor 30 by coupling 35. Digital motor 39 is connected to electrical control 41 which in turn is connected to program control 43. Electrical control 41 may be a typical electrical circuit used to drive digital stepping motors, which circuit is well known to those skilled in the application and control of stepping motors. Electrical control 41 may also have an input circuit which can convert a digital input code to a corresponding electrical signal to drive the stepping motor through a predetermined angular excursion. Circuits of this nature are well known and widely used to control the angular position of a digital stepping motor. Program control 43 may be a series of thumbwheel switches which may be rotated to produce a desired digital code to the input circuit of electrical control 41.

Silicone oil syringe 19 has fluid port or opening 45 in the side thereof connected to silicone oil reservoir syringe 47. Piston 49 is located within the interior volume of silicone oil syringe 19 and piston 51 is located within the interior volume 52 of silicone oil reservoir syringe 47. Shaft 53 is connected to piston 49 and to bracket 55, bracket 55 having a threaded opening therein which engages screw 57 to form a screw-drive mechanism. Screw 57 is connected to coupling 59 which in turn is connected to shaft 51 of digital motor 63. Digital motor 63 is connected to electrical control 65 which in turn is connected to program control 67. Electrical control 65 may be identical to electrical control 41 and program control 67 identical to program control 43.

Turning now to FIG. 2, there is illustrated a cross-sectional view of a preferred embodiment of the pick-up and dispensing probe of the invention. The first fluid capillary conduit path comprising common section 7 and separate section 9 is a short length of a thin walled capillary tubing having a minute aperture 8 located in the side thereof between common section 7 and separate section 9. Block 12, having second capillary conduit 11 drilled therein by drilling two intersecting right angle capillary lumens, is soldered to the side of the first capillary conduit path tubing so that one end of second capillary conduit path 11 intersects and mates with minute aperture 8. Fluid conduit 13, which may be a flexible plastic or teflon capillary lumen, is attached to the end of separate section 9 of the first fluid capillary conduit tubing. A short section of capillary tubing 14 is soldered into the other end of second capillary conduit path 11 in block 12. Fluid conduit 17, which may be a flexible plastic or teflon capillary lumen similar to conduit 13 is fastened to capillary tubing 14.

FIGS. 3(a), (b), (c), (d), and (e) illustrate the fluid positions within the pick-up and dispersing probe during the different operating conditions of the probe. In FIG. 3(a), the probe is shown in the fluid aspirating condition wherein fluid B, which may be a silicone oil, fills common section 7 and second fluid conduit path 11; and fluid A, which may be a saline solution fills separate section 9, forming an interface with fluid B at the end of separate section 9 adjacent to minute aperture 8.

FIG. 3(b) illustrates the fluids within the probe just after a test fluid C, which may be a blood serum, has been aspirated therein. Fluid C fills common section 7 and second capillary conduit path 11 and continues on into fluid conduit 17 interfacing with fluid B therein. Fluid A in separate section 9 interfaces with Fluid C at the end of separate section 9 adjacent to minute aperture 8.

FIG. 3(c) illustrates the position of fluid within the probe after test fluid C has been flushed from common section 7 by forcing fluid A through common section 7 to the end thereof. Fluid A fills both common section 7 and separate section 9 and forms an interface with fluid C at minute aperture 8. Fluid C fills second capillary conduit path 11 and continues upward into fluid conduit 17 where it interfaces with fluid B. The amount of fluid C contained in second capillary conduit path 11 and fluid conduit 17 depends upon the amount of test fluid C aspirated therein.

FIG. 3(d) illustrates the fluid position within the probe when a particular aliquot of test fluid C has been dispersed from conduit 17 and second conduit path 11 into common section 7. The volume size of the aliquot can be extremely small and may occupy all or a portion of common section 7, forcing fluid A therein out of the end of common section 7. In this manner, precision aliquots of one lambda or less may be obtained. The aliquot is dispersed from common section 7 by forcing fluid A from separate section 9 through common section 7 to the end thereof such that the fluids are in the position illustrated in FIG. 3(c).

FIG. 3(e) illustrates the fluid positions within the probe when all of the test fluid C has been dispersed from conduit 17 and second conduit path 11 and the probe has been flushed out by dispersing fluid A from separate section 9 through common section 7 and out of the end thereof.

Turning now to FIG. 4, a pictorial view of a preferred embodiment of the pick-up and dispersing probe is illustrated. The first capillary conduit path tubing comprising common section 7 and separate section 9 is shown soldered to block 12 containing second capillary conduit path 11 (not shown) which is connected to short section of capillary tubing 14.

Operation of the invention can best be described first by reference to FIG. 1. Piston 25 of diluent syringe 15 is positioned to open port 21 to allow fluid from diluent reservoir syringe 23 to be forced from volume 21 by piston 27 into the interior of diluent syringe 15. Piston 27 is moved into volume 28 until the diluent fluid is expelled and dispersed out of common section 7 of the pick-up and dispersing probe, thereby filling the interior volume of diluent syringe 15, fluid conduit 13 and separate and common sections 9 and 7 of the pick-up and dispersing probe. Piston 25 is then moved to close port 21, placing the diluent syringe in position for operation.

Similarly, piston 49 is moved to open port 45 in silicone oil syringe 19 to permit fluid to be forced from volume 52 of silicone oil reservoir syringe 47 by moving piston 51 into volume 52. Fluid from reservoir syringe 47 is forced into the interior volume of syringe 19, fluid conduit 17, second capillary conduit path 11 and common section 7 of the pick-up and dispersing probe. Because of the small capillary cross-sections of the first capillary conduit tubing forming common section 7 and separate section 9, a very small interface is formed between diluent fluid A (FIG. 3) and silicone oil B (FIG. 3) thereby minimizing contamination and mixing. Further, the chemical and physical properties of silicone oil B further reduce the mixing with diluent A and provide a substantially independent hydraulic fluid path within the probe.

Piston 49 is then moved into the interior of silicone oil syringe 19 closing port 45 and further dispersing the contents of silicone oil syringe 19 into fluid conduit 17 through the probe and out of common section 7. This prepares silicone oil syringe 19 for the aspiration of a test fluid into the probe with the fluids in the position shown in FIG. 3(a).

Program control 67, which may contain finger operated digital switches, programs electrical control 65 to produce a predetermined driving signal to digital motor 63 causing shaft 61 to rotate through a predetermined angle which in turn rotates screw 57 to move bracket 55 and piston 49 in a direction to increase the interior volume of silicone oil syringe 19 and aspirate test fluid C into the probe as illustrated in FIG. 3(b). The use of silicone oil provides a non-mixing interface between test fluid C and silicone oil B. Furthermore, the small cross-sectional area of the capillary tubing provides a precise interface between diluent fluid A and test fluid C at the end of separate section 9 adjacent to minute aperture 8. Since silicone oil syringe 19 may be a precision bore calibrated syringe, program control 67 can be operated to produce a precise volume change of silicone oil syringe 19 to aspirate a precise volume of test fluid C into the probe and into fluid conduit 17.

Before test fluid C is dispersed from the probe, fluid A may be forced into common section 7 of the probe as illustrated in FIG. 3(c) to remove and flush test fluid C therefrom thereby removing any surface tension drops at the end of the probe and enabling the dispersing of precision aliquots of test fluid approaching one lambda. This is done by moving piston 25 a fixed amount by operation of program control 43 to program electrical control 41 to produce a drive signal to digital motor 39 to turn shaft 37 through a predetermined angle thereby turning screw 33 to move bracket 31 and piston 25 a given amount into the internal volume of diluent syringe 15 equivalent to the volume of common section 7. The amount of diluent fluid A used to perform this dispersion need be no more than the volume of the capillary common section 7.

To disperse test fluid C, the thumb-wheel switches of program control 67 may be operated to program electrical control 65 to produce a drive signal to digital motor 63 to turn shaft 61 and screw 57 through a predetermined angle to move bracket 55 and piston 49 a precise amount corresponding to the precision volume of test fluid to be dispersed. Turning to FIG. 3(d), dispersion of test fluid C into common section 7 forces an equivalent amount of diluent fluid A contained in common section 7 out of the probe in front of the precision volume of test fluid C dispersed therein. Therefore, a very small and precise aliquot of test fluid C is forced in common section 7 which can be a fractional part of the volume of common section 7. It should be clear that volumes of test fluid C larger than common section 7 can be dispersed with equal precision. To complete the test fluid dispersion operation, piston 25 of diluent syringe 15 may be further moved a predetermined fixed amout to rinse the aliquot of test fluid C contained in common section 7 from the probe again placing the fluids in the position of FIG. 3(c). It should be noted that the amount of diluent in every dispersing action added to the test aliquot is always precisely the same and is equivalent to the volume of common section 7. Therefore, comparative tests can be made on successive test aliquots without inaccuracies caused by effects of varying dilutions.

After the last of test fluid C has been dispersed into common section 7, the section is flushed by forcing fluid A therethrough whereby the fluids take the position illustrated in FIG. 3(e). Here diluent fluid A now occupies separate section 9 and common section 7 and interfaces with silicone oil B at minute aperture 8. The probe is then flushed with silicone oil from second conduit path 11 to take the fluid position illustrated in FIG. 3(a) where the probe is ready once more for aspiration of test fluid C.

It should be clear at this point that the invention provides a precision aspirating and dispersing probe that eliminates the inaccuracies of aspiration and dispersion of fluids caused by the formation of surface tension droplets at the end of the probe. This makes it possible to obtain accuracies in fluid dispersion and aspiration heretofore unobtainable. Furthermore, the use of silicone oil as a non-mixing, non-contaminating hydraulic fluid to interface with the test fluids which are being aspirated and dispersed provides an unique advancement in achieving further precision and accuracy heretofore unobtainable in systems using air interface and other types of hydraulic fluids.

The present invention finds particular use in the field of blood serum analysis where precision aliquots of one lambda or less are desired and where dispersing into a multilicity of containers from one sample container is required. Test fluids which are blood sera may be precisely aspirated and dispersed to enable a larger number of chemical tests from a given volume of serum than heretofore possible. Since more chemical tests can be performed on a given blood sample, the amount of blood taken from a patient for a given set of tests is minimized. The smaller test volumes also enable more rapid testing since less time is required for aspirating and dispersing serum test aliquots.

It now should be apparent that the present invention provides a probe arrangement and an inert hydraulic fluid which may be employed in conjunction with a precision fluid metering system for the precise and accurate aspiration and dispersion of blood sera for chemical testing without the unwanted contamination and sample volume errors associated with the sampling systems used heretofore and with sample aliquots of smaller precision volumes than achieved heretofore.

Although particular components, etc., have been discussed in connection with a specific embodiment of a precision fluid metering probe and control systems constructed in accordance with the teachings of the present invention, others may be utilized. Furthermore, it will be understood that although an exemplary embodiment of the present invention has been disclosed and discussed, other applications and circuit arrangements are possible in that the embodiment disclosed may be subjected to various changes, modifications and substitutions without necessarily departing from the spirit of the inveniton.

Claims

What is claimed is:

1. Apparatus for the precision metering of fluids, comprising:

a first capillary conduit having a minute aperture therein, said aperture dividing said first conduit into a separate and common section, said first conduit forming a first fluid conducting path through said separate and common section;

a second capillary conduit having one end thereof intersecting said first conduit and mating with said minute aperture to form a second fluid conducting path through said second conduit and said common section of said first conduit, said minute aperture forming a first precise interface between said first fluid path and said second conduit, and the capillary cross section of said first conduit's separate section adjacent said minute aperture forming a second precise interface between said second fluid conducting path and said separate section whereby fluid can traverse said first path substantially free from contamination from fluids adjacent said first precise interface and fluids can traverse said second path substantially free from contamination from fluids adjacent said second precise interface;

a first syringe connected to the end of said first conduit separate section, said first syringe having a movable piston to change the volume thereof whereby fluids can be aspirated and dispersed through said first fluid path;

a second syringe connected to the end of said second conduit, said second syringe having a movable piston to change the volume thereof whereby fluids can be aspirated and dispersed through said second fluid path;

a first fluid contained within said first syringe and within said first conduit separate section up to said second precise interface whereby decreasing the volume of said first syringe by a precise amount forces said first fluid past said second precise interface and into said first conduit common section thereby displacing any fluid contained in said common section; and

a second fluid contained in said second syringe and within said second conduit and said common section whereby increasing the volume of said second syringe aspirates through said common section and into said second conduit a test fluid into which the end of said common section is immersed, said test fluid in said common section being displaced therefrom by said first fluid, and whereby decreasing said volume of said second syringe in metered increments dispenses said test fluid in precise amounts from said second conduit into said common section wherefrom said precise amounts may be displaced by said first fluid.

2. The apparatus as described in claim 1 wherein said second fluid is a silicone oil.

3. The apparatus as described in claim 2 wherein said first fluid is a saline solution and said test fluid is blood serum.

4. The apparatus as described in claim 3 further including;

first coupling means connected to said piston of said first syringe; and

a first digital stepping motor connected to said first coupling means whereby said piston of said first syringe is moved to increase and decrease the volume of said first syringe.

5. The apparatus as described in claim 4 further including:

second coupling means connected to said piston of said second syringe; and

a second digital stepping motor connected to said second coupling means whereby said piston of said second syringe is moved to increase and decrease the volume of said second syringe.

6. The apparatus as described in claim 5 whereby each of said first and second coupling means, respectively, is a screw drive mechanism comprising:

a threaded shaft attached to and turned by said digital stepping motor; and

means having a threaded opening therein for engaging said threaded shaft, said means being attached to said piston of said syringe whereby said volume of said syringe is increased and decreased.

7. The apparatus as described in claim 6 further including:

a pair of electronic circuit means each being connected to one digital motor for driving said digital motor; and

a pair of control means each separately attached to one of said pair of electronic circuit means for generating a coded electronic signal to said one of each pair of circuit means whereby each of said digital motors is driven in steps related to said coded signal.

8. The apparatus as described in claim 7 further including:

a reservoir syringe for containing a reserve of saline solution; and

a fluid port located in the side of said second syringe and connected to said reservoir syringe for receiving fluid from said reservoir syringe.

9. The apparatus as described in claim 8 further including:

a reservoir syringe for containing a reserve of silicone oil fluid; and

a fluid port located in the side of said first syringe and connected to said reservoir syringe for receiving fluid from said reservoir syringe.