SAMPLING APPARATUS AND METHOD

Abstract: Sampler apparatus and method are provided and in­ clude both closed and open tube samplers, and selector valve operable to select therebetween for sample supply to automated sample analysis apparatus. A shear valve di­ vides the samples into separate sample quantities for in­ dependent sample quantity analysis by multi-channel sam­ ple analysis apparatus. A pressure equilibration chamber prevents vacuum build-up in the closed tube sampler to insure the supply of consistent sample quantities therefrom. A source of a pressurized rinse solution is provided; and is operatively connected to the sampler apparatus in such manner as to insure the particularly thorough rinsing and cleansing of all relevant sampler components to remove sample residue therefrom between sampling operations, thereby reducing sample carryover to levels below those of clinical significance.

Description: This invention relates to new and improved sampling apparatus and method which are capable of automated sampling from both closed and open sample tubes attendant sample analysis. Although a number of closed tube samplers are known in the prior art, most relevantly in this instance the closed tube sampler included in the hematology instrument as marketed by Coulter Electronics, Inc., Hialeah, Florida as the Coulter "S-PLUS VI," and the closed tube sampler included in the hematology instrument as marketed by Cortex Research Corporation, Northbrook, Illinois under the Trademark "Double Helix;" it may be understood that neither of these prior art closed tube samplers is configured or operable in the manner of the novel sampler of this invention to provide for versatility of application in terms of the immediately available option of automatically switching between closed and open tube sampling through use of simple selector valve means and essentially the same sample supply means without requirement for external modification in sampler configuration; to provide for simplicity of configuration and operation in terms of utilizing essentially the same flow paths for sample supply and for inter-sample sampler rinsing; or to provide for significantly increased sample analysis accuracy in terms of insuring the consistent supply of precisely determined and readily reproducible sample volumes attendant repeated sampling from the same closed sample tube, and in terms of the absolute minimization of sample carryover to levels below those of clinical significance. Too, and although a particularly wide variety of open tube samplers are known in the prior art, most relevantly in this instance the open tube samplers as disclosed in United States Patents 3,719,086, 3,756,459, 3,759,667, 3,912,452 and 4,065,973, it may be understood that none of these prior art open tube samplers is configured or operable in the manner of the novel sampler of this invention to provide for versatility of application in terms of the immediately available option of switching from open to closed tube sampling; to provide for simplicity of configuration in terms of utilizing essentially the same flow paths for sample supply and for inter-sample sampler rinsing; or to provide for significantly increased sample analysis accuracy in terms of the absolute minimization of sample carryover to levels below those of clinical significance for both open and closed tube sampling. As disclosed herein, the new and improved sampler apparatus and method of my invention comprise a closed tube sampler, an open tube sampler, sample supply means operatively associated therewith and operable to supply samples therefrom to automated sample analysis apparatus, and selector valve means operatively associated with the closed and open tube samplers, and the sample supply means, and operable to enable selection between the closed and open tube samplers for sample supply to the analysis apparatus. Shear valve means operate to divide the thusly supplied samples into separate sample quantities for concomitant, independent sample quantity analysis by multi-channel sample analysis apparatus. The sample supply means include pressure equalization means which are operable upon closed tube sampler selection and operation to prevent vacuum build-up in the same, thereby insuring consistent sample quantity supply from the closed tube sampler with attendant maximization of the accuracy of the sample analysis results. Rinse means are operatively associated with the closed and open tube samplers, the sample supply means, the selector valve means, and the shear valve means, and are operable to particularly thoroughly rinse and cleanse the same of sample residue between sampling operations, thereby reducing sample carryover to levels below those of clinical significance and further maximizing the accuracy of the sample analysis results. The advantages of my invention are believed made clear by the following detailed description thereof taken in conjunction with the accompanying drawings wherein: FIG. l is an essentially diagrammatic view of a new and improved sampler representatively configured and operable in accordance with the teachings of my invention, as depicted in operable relationship with sample analysis apparatus, and includes certain components depicted in cross-section; FIG. 2 is an essentailly cross-sectional view of the closed tube sampler of FIG. l in a different operational condition; FIG. 3 is essentially cross-sectional view of the open tube sampler of FIG. l in a different operational condition; FIG. 4 is an essentially cross-sectional view of the sample valve of FIG. l in a different operational condition; FIG. 5 is an essentially cross-sectional view of the open tube sampler and selector valve of FIG. l in different operational conditions; and FIG. 6 is an essentially cross-sectional view of the analysis apparatus reagent valve and metering pump of FIG. l in different operational conditions. Referring to FIGS. l and 2 of the drawings, a new and improved sampler representatively configured and operable in accordance with the teachings of my invention is indicated generally at l0; and comprises a closed tube sampler as indicated generally at l2, and an open tube sampler as indicated generally at l4. Sample supply and sampler rinse apparatus are indicated generally at l6, and a sample valve is indicated generally at l8; and a selector valve is indicated generally at 20, and is operable to selectively connect the sample supply and sampler rinse apparatus l6 to either of the closed tube sampler l2 or the open tube sampler l4 for sample supply to the sample valve l8, and subsequent rinse of the latter and of the relevant sampler. Automated sample analysis apparatus are indicated schematically at 22; and are depicted in operable relationship with the sampler 10 for automated analysis of the samples as supplied thereto from sample valve l8. A controller is schematically depicted at 24, and is operable to control the operation of the indicated sampler and sample analysis apparatus components as described in greater detail hereinbelow. The closed tube sampler l2 comprises a closed sample tube holding assembly 26 which includes upper and lower, relatively movable plates 28 and 30. Upper plate 28 includes an upstanding, open-ended generally cylindrical sample tube insertion guide 32 for guidance and support of an inverted, closed sample-containing tube 34 therein as shown. For a representative application of the sampler l0 of my invention, sample tube 34 may, for example, take the form of that marketed under the Trademark "Vacutainer" by the Becton-Dickinson Company of East Rutherford, New Jersey, and will include therein a whole blood sample 36 as aspirated directly thereinto from the arm of a patient and retained therein as shown by a stopper 38 of any appropriately inert and self-sealing material such as a suitable rubber. Tube 34 may be manually inserted into tube insertion guide and support 32, or may be mechanically inserted thereinto by any appropriate tube insertion device, not shown, as well known and understood by those skilled in this art. A jacketed sampling needle assembly 40, including a sampling needle 4l, is fixedly mounted as shown by screw-threaded mounting collar 42 in stepped and internally threaded bore 44 of lower plate 30, and extends upwardly therefrom through aligned bore 46 in upper plate 28 to establish a fluid-tight seal therebetween, albeit with freedom for relative movement. A bore 48 connects bore 46 via vacuum conduit 50 to waste through a suitable source of vacuum, not shown; while a vent bore 52 of small diameter connects bore 46 to atmosphere. Preferably, bore 46 and thus sampling needle 4l are slightly off-center or eccentric relative to tube insertion guide 32 and thus tube stopper 38 for purposes made clear hereinbelow. Closed tube holding assembly drive means are indicated generally at 54, and comprise a fluid motor having a cylinder 56 fixedly mounted in any appropriate manner, for example spot welding as indicated at 57, on upper plate 28, and a double-acting piston 60 reciprocatable therein by pressurized fluid from source 62 as supplied to opposite faces of piston 60 through four way valve as schematically indicated at 64 via conduits 66, 68 and 70. Four way valve 64 is preferably operated by an electrically controllable device, for example an electric drive motor as schematically depicted at 65, and is rotatable thereby between the valve positions of FIGS. l and 2. A piston rod 72 extends as shown downwardly from piston 60 through sealing means 73 and bore 74 in upper plate 28, and is fixedly secured to lower plate 30 by an attachment screw 76 which extends through stepped bore 78 in the lower plate 30 into threaded bore 80 in the bottom face of piston rod 72. With closed sample tube holding assembly 26 configured as described, it will be clear that with upper and lower plates 28 and 30 in the abutting or "closed" position thereof of FIG. l, attendant supply of pressurized fluid from source 62 to cylinder 56 below piston 60 via valve 64 and conduits 66 and 70, sampling needle 40 will be effective to pierce tube stopper 38 and extend into fluid flow communication with sample 36 in closed tube 34 as supported in guide 32. Conversely, with upper and lower plates moved to the separated or "open" position thereof of FIG. 2 through supply of pressurized fluid from source 62 to cylinder 56 above piston 60 via valve 64 and conduits 66 and 68, sampling needle 40 will be withdrawn from stopper 38 and exposed in upper plate bore 46 to vacuum via plate bore 48 A flexible sample supply conduit 82 of any appropriately inert, and preferably transparent, material, for example Teflon, connects jacketed sampling needle 40 via sampling needle connector 83 to selector valve 20. Open tube sampler 14 comprises an off-take probe 84 which extends as shown into a sample 86 contained in an upstanding open sample tube 88 which is positioned relative thereto as shown in FIG. l for withdrawal by aspiration by the probe of a predetermined sample portion therefrom. Tube 88 may be manually presented to probe 84, or may be mechanically presented thereto by any appropriate tube presentation device, not shown, as well known and understood by those skilled in this art. For a representative application of the sampler 10 of my invention, tube 88 may take the form of a "Vacutainer," and sample 86 may again be a whole blood sample as aspirated directly thereinto from the arm of a patient. A generally cylindrical probe wash sleeve is indicated at 90 and comprises a stepped bore 92 which includes an enlarged bore portion 94 through which probe 84 extends as shown with freedom for relative movement therebetween. A generally fluid-tight seal is formed between probe 84 and the upper portion of bore 92. Wash sleeve 90 further comprises spaced rinse solution and vacuum bores 97 and 98 extending as shown generally transversely thereof into communication with enlarged sleeve bore portion 94. Bore 97 is operable via flexible conduit 100 to supply a pressurized rinse solution from a source 102 thereof to the upper end of bore portion 94; while bore 98 is operable via flexible conduit 104 to connect the lower end of bore portion 94 to waste through a suitable vacuum source, not shown. Wash sleeve drive means are depicted schematically at 96, and are operatively connected as indicated to wash sleeve 90 to drive the same between the positions thereof of FIGS. l and 3 relative to off-take probe 84; upon removal of course of the open tube 88 from the position thereof depicted in FIG. l. Drive means 96 may, for example, take the form of the electrically controllable fluid motor 54 which forms the closed tube holding assembly drive means; in which instance the motor piston rod would be connected to the wash sleeve 90 to reciprocate the same between the wash sleeve positions of FIGS. l and 3. Valves taking for example the form of suitable pinch vlaves are indicated schematically indicated at l05 and l07, and are respectively operatively associated with flexible rinse and vacuum conduits l00 and l04 as shown to control fluid flow there-through. Valves l05 and l07 are prefereably operated by electrically controllable devices, for example solenoids, as indicated schematically at l09 and lll. A flexible sample supply conduit l06 connects off-take probe 84 to selector valve 20. Sample supply and sampler rinse apparatus l6 comprise a pressure equilibration chamber l08 which is connected via flexible conduit ll0 as indicated to waste through a suitable vacuum source, not shown. An electrically operable conductivity detector is schematically depicted at ll2, and includes interconnected flow passages ll4, ll6 and ll7 extending therethrough as shown. A flexible conduit ll8 connects conductivity detector passage ll6 to equilibration chamber l08, and a flexible conduit l20 connects conductivity detector flow passage ll7 to pressurized rinse source l02. As well known and understood by those skilled in this art, conductivity detector ll2 is operable to detect the presence of sample fluids in passages ll4 and ll7, on the basis of the resultant conductivity changes thereacross, and to generate and output an electrical signal indicative thereof. Valves taking the form of pinch valves are schematically depicted at l22, l24 and l26, and are respectively operatively associated as shown with flexible conduits ll0, ll8 and l20 to control fluid flow therethrough. Valves l22, l24 and l26 are preferably operated by electrically controllable devices, for example solenoids, as schematically depicted at l23, l25 and l27, respectively. The sample valve l8 takes the form of a shear valve l28 which comprises a stationary, generally cylindrical outer valve body part l29 having a bore l30 formed therein, and a generally cylindrical inner valve body part l3l disposed as shown in generally fluid-tight manner in bore l30 and rotable relative thereto between the positions thereof of FIGS. l and 4 by operatively connected electrically operated drive means preferably taking the form of an electric drive motor as schematically depicted at l33. Inner valve body part l3l comprises spaced sample fluid loops or passages l32, l34, l36 and l38 formed therein as shown; while outer valve body part l29 comprises sample fluid passages l39 and l40, and spaced sample fluid loops or passages l42, l44 and l46 which are respectively precisely alignable with inner valve body loops l2, l34, l36 and l38 to form a continuous sample fluid passage extending through the sample valve from outer valve body passages l39 to l40 when the sample valve is in the position thereof as depicted in FIG. l. Further included in the outer valve body part l29 of the shear valve l28 are spaced fluid passage pairs l50 and l52, l54 and l56, l58 and l60, and l62 and l64, which are respectively precisely alignable as shown with inner valve body part loops l32, l34, l36 and l38 with inner valve body part l3l rotated to the FIG. 4 position thereof by drive motor l33 to form four discrete sample fluid flow passages extending through the valve, none of which are in fluid folow communication with closed or open tube samplers l2 and l4 or with the sample and sampler rinse supply apparatus l6. A flexible conduit l70 connects outer valve body passage l39 to flow passage ll4 in conductivity detector ll2. Selector valve 20 comprises a three way valve as schematically depicted at l72 which is connected as shown by flexible conduit l74 to passage l40 of shear valve l28. Three way valve is rotatable between the positions thereof of FIG. l and FIGS. 3 and 5 by operatively connected, electrically operated drive means taking, for example, the form of an electric drive motor as schematically depicted at l76. with the three way valve l72 in the position thereof of FIG. l, it will be clear that closed tube sampler l0 will be operatively connected therethrough to shear valve l28 via conduits 82 and l74; while open tube sampler l4 will be effectively disconnected and isolated from the sample supply circuit of the sampler apparatus l0. Conversely, with the three way valve l72 in the position thereof of FIG. 5, it will be clear that the open tube sampler l4 will be operatively connected therethrough to shear valve l28 via conduits l06 and l74; while closed tube sampler l2 will be effectively disconnected and isolated from the sample supply circuit of the sampler apparatus l0. For use with a sample valve l8 taking the form of shear valve l28 which is operable as depicted and described to form four separate and discrete sample loops l32, l34, l36 and l38 with the inner valve body part l3l rotated by drive motor l33 to the position thereof of FIG. 4, it will be clear to those skilled in this art that the sample analysis apparatus 22 may advantageously include four discrete, albeit concomitantly operable, automated sample analysis channels operatively associated with said shear valve on the basis of one of said sample analysis channels for each of said sample loops. One of these sample analysis channels, as indicated generally at l75, is representatively depicted in some detail, albeit schematically, in FIG. l; while the remaining three of such sample analysis channels are depicted in block diagram form at l76, l77 and l78, all in operative relationship with the shear valve l28. As schematically depicted in FIG. l, automated sample analysis channel l75 comprises a reagent(s) source l80, a reagent metering pump l82, a three way reagent valve l84, and a sample-reagent reaction and analysis chamber l86. Reagent metering pump l82 comprises a piston l88 which is reciprocatable in a cylinder l89 by an electric drive motor l90. A flexible conduit l92 connects reagent(s) source l80 to reagent valve l84; while flexible conduits l94 and l96 respectively connect reagent valve l84 and reaction and analysis chamber l86 to passages l58 and l60 in shear valve l28, thus effectively connecting sample analysis apparatus channel l75 to shear valve sample loop l36 when the shear vlalve l28 is in the FIG. 4 position thereof. A flexible conduit l97 connects reagent metering pump l82 to three way valve l84; while electrically controllable drive means, preferably taking the form of an electric drive motor as depicted schematically at l98 are operatively connected as indicated to reagent valve l84 and are operable to rotate the same between the positions thereof of FIG. l and FIG. 6 to either connect reagent pump l82 to source l80 or to the shear valve l28. Further included in automated sample analysis channel l75 are sample anlysis means taking, for example, the form of a light source 200, such as a laser, and a lightsensitive detector 202, respectively operatively associated with sample-reagent reaction and analysis chamber l86 and operable to automatically analyze reacted samples as contained therein in manner(s) well known and understood by those skilled in this art. Flexible conduits 204 and 206, 208 and 2l0, and 2l2 and 2l4, are provided to respectively connect sample analysis apparatus channels l76, l77 and l78 as shown to shear valve sample loops l34, l32 and l38 when the inner valve body part l3l is rotated to the position thereof of FIG. 4; and it will be clear that the respective sample analysis apparatus channels l76, l77 and l78 may take any of a wide variety of configurations compatible with automated sample analysis. Controller 24 may, for example, take the form of an appropriately programmable microprocessor device which is operable as indicated through non-illustrated power supply devices to electrically control, i.e. start, stop, sequence and time, the respective operations of the sampler and sample analysis apparatus components as indicated on FIG. l of the drawings. For operation of the sampler l0 of my invention to supply a sample from closed tube sampler l2 to sample analysis apparatus 22, and with no tube 34 initially in place in tube insertion and support guide 32, it will be understood that controller 24 would be activated to open pinch valve l24, close pinch valves l22, l26, l05 and l07, and position shear valve l28, three way valve l72 and four way valve 64 as depicted in FIG. l. This effectively isolates open tube sampler l4 from the sampler l0, and brings tube holding assembly 26 to the "closed" position thereof of FIG. l; and insures ambient atmospheric pressure in equilibration chamber l08 via the open and exposed tip of sampling needle 4l through the relevant connected conduits and fluid passages. Concomitantly, controller 24 operates to drive reagent valve l84 to the FIG. 6 position thereof, and to drive reagent metering pump piston l88 downwardly as shown to bottom dead center to aspirate reagent(s) from source l80 via conduit l92 and charge pump cylinder l89 therewith. Closed sample tube 34 with stopper 38 firmly in place is then manually inserted into tube insertion guide 32 and forced downwardly until the stopper abuts and comes to rest at the upper surface of plate 28. This results in needle 4l piercing stopper 38 and extending as shown into fluid flow communication with sample 36. Under these circumstances, it will be clear that vacuum build-up in closed tube 34 above sample 36, as might otherwise develop attendant repetitive sample aspiration from the same closed sample tube, will be advantageously eliminated by the flow of the necessary quantity of air at ambient atmospheric pressure from the equilibration chamber l08 to the interior of closed tube 34 above the sample 36 via the open end of needle 4l; it being understood by those skilled in this art that vacuum build-up of the nature under discussion in closed tube 34 could very well result in the formation and inclusion of micro-bubbles in sample(s) as aspirated therefrom with attendant reduction in the overall quantity of sample available for analysis, and significant and contemporarilly unacceptable degradation in sample analysis accuracy. The problem of micro-bubble formation in aspirated sample(s) is of particular concern in contemporary sample analysis apparatus wherein increasingly small quantities, for example 100 micro-liters, of sample are aspirated for supply to sample analysis apparatus, and wherein the accuracy of the sample analysis results are closely predicated upon the availability in each instance of a precisely known sample quantity for analysis; in this instance the respective sample quantities as contained in shear valve loops l32, l34, l36 and l38 as described in detail hereinbelow. Too, in those instances wherein closed tube 34 is constituted by a "Vacutainer," and wherein a short "pull" from a patient results in significantly less than an optimal quantity of blood sample available therein for analysis, it will be clear to those skilled in this art that the addition of air at ambient atmospheric pressure to closed tube 34 as described above sample 36 may prove essential as a practical matter to permit satisfactory sample aspiration therefrom. Following pressure equilibration as above between equilibration chamber l08 and closed sample tube 34 --this in reality is accomplished almost instantaneously upon the entry of sampling needle into the closed tube-- controller 24 operates to open pinch valve l22, thus connecting the relevant vacuum source through conduit ll0 to sampling needle 4l, whereby sample 36 will be aspirated from closed tube 34 via needle 4l, connector 83, conduit 82, valve l72 and conduit l74 to flow into and through and fill connected shear valve passages and loops l40, l38, l46, l36, l44, l34, l42, l32 and l39, and to flow from the latter via conduit l70 into passage ll4 of conductivity detector ll2. Upon the arrival and detection of the leading edge of the thusly aspirated sample in the conductivity detector ll2, the latter will operate to signal controller 24 to close pinch valve l24 to discontinue sample aspiration from closed tube 34. Controller 24 then operates to rotate the inner body part l3l of shear valve l28 to the FIG. 4 position thereof, thus effectively shearing the sample-filled flow passage through valve l28 into four discrete, and precisely volumetrically determined, sample segments as respectively contained in shear valve loops l36, l34, l32 and l38 which are now respectively placed in fluid flow communication with sample analysis apparatus channels l75, l76, l77 and l78 via valve passages l58 and l60 and conduits l94 and l96, valve passages l54 and l56 and conduits 204 and 206, valve passages l52 and l50 and conduits 208 and 2l0, and valve passages l64 and l62 and conduits 2l2 and 2l4. For sample analysis by sample analysis apparatus channel l75, controller 24 then operates to return reagent valve l84 to the FIG. l position thereof and to drive reagent metering pump piston l88 to top dead center to pump a precisely metered reagent quantity into conduit l94 through valve l84, thus inserting the sample contained in shear valve loop l36 into the reagent flow path formed by conduit l94, valve passage l58, loop l36, valve passage l60 and conduit l96, and flushing the resultant sample-reagent solution into reaction and analysis chamber l86 for thorough sample-reagent mixing and reaction, and automated sample analysis attendant subsequent activation by controller 24 of light energy source 200 and detector 202. Controller 24 then returns reagent valve l84 to the FIG. 6 position thereof for re-charging as described of reagent pump l82 with reagent from source l80. Sample analysis apparatus channels l76, l77 and l78, which may be of the same or different configurations than analysis channel l75, are concomitantly operated by contoller 24 to acquire, react (if required), and analyze the respective sample quantities from shear valve loops l34, l32 and l38. Controller 24 then operates to return shear valve l28 to the FIG. l position thereof thus re-establishing the continuous flow path therethrough; and to rotate four way valve 64 to the FIG. 2 position thereof, thereby operating fluid motor 54 to drive the closed tube holding assembly 26 to the "open" position thereof of FIG. 2. This retracts the tip of sampling needle 4l into bore 46 in upper plate 28, thereby exposing the same to vacuum via the now uncovered vacuum bore 48 and conduit 50. Particularly thorough rinsing and cleansing of the sample-contaminated flow path from the open tip of needle 4l to and through the shear valve l28 to minimize sample carryover, e.g. the contamination of a succeeding sample by the residue of a preceding sample, and maximize the accuracy of subsequent sample analysis, is then initiated by the re-opening of pinch valve l24 via controller 24 to re-connect the sampling needle 4l to the relevant vacuum source and thereby aspirate the vast bulk of the sample remaining in needle 4l, connector 83, conduit 82, three way valve l72, conduit l74, shear valve passages and loops l40, l38, l46, l36, l44, l34, l42, l32 and l39, conduit l70, and conductivity detector passage ll4 to waste through conductivity detector passage ll6, conduit ll8, equilibration chamber l08 and conduit ll0, respectively. Of course, the atmospheric air required by this aspiration of remaining sample to waste is provided by vent bore 52 in the upper plate 28 of the closed tube holding assembly 26. Controller 24 then operates to close pinch valve l24 and open pinch valve l26, thereby providing for the forceful flow of pressurized rinse solution from source l02, through conduit l20, conductivity detector passages ll7 and ll4, conduit l70, the above-specified connected shear valve passages and loops, conduit l74, three way valve l72, conduit 82, connector 83 and jacketed sampling needle 40, respectively, to waste via bore 46, vacuum bore 48 and conduit 50. This results in the particularly effective and thorough rinsing and cleansing, by forceful rinse solution back flushing as described, of the entire sample sample supply path from the tip of sampling needle 4l to and through the shear valve l28; and, in addition, results in like manner in the particularly thorough rinsing and cleansing of the exposed outer surface of the tip of sampling needle 4l as the rinse solution flows from the open needle tip downwardly and completely around that surface on its way to vacuum bore 48. Controller 24 then operates to re-close pinch valve l26 and re-open pinch valve l24, thereby discontinuing pressurized rinse solution supply, evacuating the rinse solution from the entire sample supply path of interest to waste via conduit ll0, and subsequently effectively air-drying that entire sample supply path and the exposed outer surface of the sampling needle tip. Thus, all relevant sampler and valve components are left essentially clean and dry, sample carryover with regard to a succeeding sample reduced to an absolute and clinically insignificant minimum, and the accuracy of succeeding sample analysis results maximized. Closed sample tube 34 is manually removed from tube insertion and support guide 32 on the tube holding assembly 26 at or before the completion of the rinsing and drying operation. At the completion of the rinsing and drying operation, controller operates to re-close pinch valve l22 and return four way valve 64 to the FIG. l position thereof, thus again effectively insuring ambient atmospheric pressure in the equilibration chamber l08, and returning the closed tube holding assembly 26 to the "closed" position thereof of FIG. l in readiness for repetition of the closed tube sampling and analysis cycle as described. Sampling needle 4l is disposed somewhat off-center vis-a-vis closed tube insertion and support guide 32 to reduce from virtual certainty the probability attendant subsequent re-introduction of the same closed sample tube 34 to closed tube sampler l2 that needle 4l will pierce the tube stopper 38 at precisely the same location, thereby unduly weakening the latter and introducing the unacceptable possibility of leakage at the point where the needle pierces the stopper. For operation of the sampler l0 of my invention to supply a sample from open tube sampler l4 to sample analysis apparatus 22 for analysis, and with a sample-containing open tube 88 presented as depicted in FIG. l to immerse off-take probe 84 in the sample 86 and wash sleeve 90 positioned as in FIG. l, it will be understood that controller 24 would be activated to close pinch valves l05,l26 and l07, open pinch valves l24 and l22, and position three way valve l72 and shear valve l28 as in FIG. l. This effectively isolates closed tube sampler l2 from the sampler l0, and results in the aspiration and flow under the influence of the relevant vacuum source of the sample 86 from open tube 88 via the open end of off-take probe 84, conduit l06, three way valve l72, conduit l74, the above-specified connected passages and loops of shear valve l28, and conduit l70, into passage ll4 of the conductivity detector ll2, respectively, thus again resulting in the filling of the shear valve sample loops l38, l36, l34 and l32 with sample. Concomitantly, controller 24 would operate sample analysis channel l75 to charge reagent metering pump l82 with reagent(s) as described hereinabove. Upon detection of the leading edge of sample 86 in conductivity detector passage ll4, the detector will signal controller 24 to close pinch valve l24, thus discontinuing further sample aspiration from open tube 88, and to rotate shear valve l28 to the FIG. 4 position thereof. Sample analysis channels l75, l76, l77 and l78 are then operated by controller 24 to acquire, react (if required in all instances), and automatically analyze the respective sample quantities from shear valve loops l36, l32, l34 and l38, all as described in some detail hereinabove with regard to the operation of the closed tube sampler l2; and open sample tube 88 is removed from registration with the off-take probe 84. Following sample quantity acquisition as described by analysis apparatus 22, controller 24 operates to rotate shear valve l28 back to the FIG. l position thereof, thus re-establishing the continuous flow path therethrough, and to re-open pinch valve l24 to aspirate to waste most of the sample 86 remaining in the probe 84, conduit l06, selector valve l72, conduit l74, and the re-connected shear valve passages and loops, respectively, through conduit l70, detector passages ll4 and ll6, conduit ll8, chamber l08 and conduit ll0. Concomitantly, controller 24 operates to open pinch valves l05 and l07, thus forcefully introducing the pressurized rinse solution from source l02 via conduit l00 and wash sleeve bore 97 at the top of wash sleeve bore portion 94 to surround and forcefully contact the outer surface of the off-take probe 84, and withdrawing the thusly introduced rinse solution from the bottom of wash sleeve bore portion 94 to waste through sleeve vacuum bore 98 and conduit l04. Controller 24 now also operates to actuate wash sleeve drive motor 96 to drive the thusly operating wash sleeve from the FIG. l to FIG. 3 position thereof, thus effectively causing the operating wash sleeve to traverse substantially the entire outer surface of the off-take probe 84 thereby thoroughly rinsing the same and removing therefrom the residue of the sample 86 therefrom. As the wash sleeve 90 reaches the FIg. 3 position thereof, it will be understood that the vacuum existing in the tip portion of probe 84 will operate to aspirate the rinse solution from wash sleeve rinse solution bore 97, as mixed of necessity with some measure of ambient atmospheric air, into the open probe tip for flow following the remaining sample as described to waste via conduit ll0. As well understood by those skilled in this art, this flowing mixture of air, in the form of air bubbles, and the rinse solution, will have a particularly effective cleansing action on the interior of probe 84, conduit l06, selector valve l72, conduit l04, and the relevant connected passages and loops of shear valve l28 with regard to the particularly thorough removal of the residue of sample 86 therefrom. Controller 24 then operates to close pinch valves l05 and l24, and to open pinch valve l26, thereby discontinuing rinse solution supply to the wash sleeve 90, and commencing rinse solution supply to the probe 84 via conduit l20, detector passages ll7 and ll4, conduit l70, the relevant connected passages and loops of shear valve l28, conduit l74, selector valve l72, conduit l06 and probe 84, thereby backflushing the same with rinse solution against the direction of sample flow therein for additional, particularly thorough and effective cleansing thereof with regard to the residue of sample 86. As this backflushing rinse solution exits the tip of probe 84, the same is simply aspirated to waste via wash sleeve vacuum bore 98 and conduit l04, thus preventing contaminated rinse solution spillage at the situs of operation of sampler l0. Of particular significance with regard to probe backflushing in instances wherein the sample(s) of interest are constituted by whole blood samples is the demonstrated effectiveness of the same with regard to removal of otherwise difficult-to-remove fibrinogen, or clotted blood fibrin materials. At the completion of probe and sample supply means backflushing as described, controller 24 operates to close pinch valve l26 and open pinch valve l24 to aspirate the rinse solution remaining in the probe 84, conduit l06, selector valve l72, conduit l74, the relevant connected passages and loops of shear valve l28, to waste via conduit l70, detector passages ll4 and ll6, conduit ll8, chamber l08 and conduit ll0, respectively, thus effectively again flushing the same with rinse solution in the direction of sample flow to complete the particularly thorough cleansing thereof with rinse solution vis-a-vis the residue of sample 86. Ambient atmospheric air will, of course, be aspirated into probe 84 following the aspiration of the remaining rinse solution therefrom as described to waste to air-dry the same, and all other relevant sampler components, to complete the cleansing thereof. Concomitantly, controller 24 operates to actuate wash sleeve drive motor 96 to return the wash sleeve 90 to the FIG. l position thereof, thus effectively air-drying the same due to the flow of ambient atmospheric air around the probe into wash sleeve vacuum bore 98, to thus complete the cleansing of the probe exterior. At the completion of the above, controller 24 operates to re-close pinch valves l22 and l07 to prepare open tube sampler l4 for a succeeding cycle of operation as described upon presentation of another open sample-containing tube to the off-take probe 84 as described. Although disclosed hereinabove as stationary relative to upper closed tube holding assembly plate 28, it will be clear that tube insertion and support guide 34 may be moveable relative thereto taking, for example, the form of a plurality of such tube insertion and support guides as may be disposed in manner well understood by those skilled in this art on a turntable or like device and which are indexable in turn into the depicted operational position for sampling in turn from the closed sample-containing tubes as inserted and supported therein. Although disclosed hereinabove by way of representative example as applied to the sampling and analysis of blood samples, it will be clear to those skilled in this art that the apparatus and method of my invention are by no means limited to use with samples as constituted by blood. Various changes may, of course, be made in the hereindisclosed preferred embodiment of my invention without departing from the scope thereof as defined by the appended claims.

Claims: Sampler apparatus for supplying samples to sample analysis apparatus and comprising, a closed tube sampler (12), an open tube sampler (14), sample supply means (16) operatively associated with said closed tube sampler (12) and said open tube sampler (14) and operable to supply samples as provided thereto by said samplers (13, 14) to sample analysis apparatus (22), and selector valve means (20) operatively associated with said closed tube sampler (12), said open tube sampler (14), and said sample supply means (16), respectively, and operable to select between said closed tube sampler (12) and said open tube sampler (14) for the provision of samples to said sample supply means (16). Sampler apparatus as in Claim 1 further comprising, rinse means (16) operatively associated with said closed tube sampler (12), said open tube sampler (14), said sample supply means (16), and said selector valve means (20), respectively, and operable to rinse said closed tube sampler (12), said open tube sample (14), and said sample supply means (16), said selector valve means (20). being further operable to select between said closed tube sampler (12) and said open tube sampler (14) for rinse by said rinse means (16). Sampler apparatus as in Claims 1 or 2 further comprising, means (18) operatively associated with said sample supply means (16) and said rinse means (16), and operable to divide samples as supplied thereto by said sample supply means (16) into separate sample quantities for independent sample quantity analysis, said rinse means (16) being operable to rinse said sample dividing means (18) attendant the rinse of said sample supply means (16). Sampler apparatus as in Claims 1, 2 or 3 which include means to supply samples from a closed sample container (34) by introducing sample aspiration means (40) thereinto, said sample supply means (16) including, means operatively associated with said sample aspiration means (40) and operable upon the introduction thereof into said closed sample container (34) to equalize the pressure in said container (34) with ambient atmospheric pressure prior to sample aspiration, thereby inhibiting vacuum build-up in said closed sample container (34) upon the aspiration of samples therefrom, said pressure equalization means comprising a pressure equilibration chamber (108) operatively connected to said sample aspiration means (40), said sampler apparatus further comprising, means to supply samples from an open sample container (88) by introducing sample aspiration means (84) thereto, and selector means (20) operatively associated with said closed and open sample container sample supply means (16) and operable to select therebetween for sample supply from said sampler apparatus. Sampler apparatus as in any one of claims, 2 - 4 further including means (54) to remove said sample aspiration means (40) from said closed sample container (34) following sample aspiration, and said rinse means (16) operatively connected to said sample supply means (16) and operable upon the removal of said sample aspiration means (40) from said closed sample container (34) following sample aspiration therefrom to flow a rinse through said sample supply means (16) and said sample aspiration means (40) against the direction of aspirated sample flow therethrough, thereby backflushing said sample supply means (16) and said sample aspiration means (40) to remove aspirated sample residue therefrom, said sample aspiration means (40) comprise a sampling needle (41), and wherein said rinse means (16) are operable to flow said rinse solution through the interior of said sampling needle (41) and around the exterior thereof to remove aspirated sample residue from both the interior and exterior of said sampling needle (41) and wherein said sampling needle (41) is generally vertically oriented upon the flow of said rinse solution therethrough. Sampler apparatus as in any one of claims 4 or 5 wherein said sample supply means (16) are further operable to flow said rinse therefrom and from said sample aspiration means (40) in the direction of aspirated sample flow therethrough, thereby flushing said sample supply means (16) and said sample aspiration means (40) to remove aspirated sample residue therefrom. Sampler apparatus as in any one of claims 4 to 6 wherein said container (34) comprises a generally circular stopper (38) closing the same, and said sampling needle (41) is operable to pierce said stopper (38) for sample aspiration from said container (34), said sampling needle (41) being disposed off-center relative to said container stopper (38) whereby said sampling needle (41) will not pierce the center of said stopper (38) attendant sample aspiration from said container. Sampler apparatus as in any one of claims 2 to 7 wherein said rinse means (16) are operatively connectable by said selector means (24) to said open sample container sample supply (16) and sample aspiration means (84), said rinse means (16) being operable upon such connection following sample aspiration from said open sample container (88) to flow a rinse through said open sample container sample supply (16) and sample aspiration means (84) against the direction of aspirated sample flow therethrough, thereby backflushing said open sample container sample supply (16) and sample aspiration means (84) to remove aspirated sample residue therefrom. Sampler apparatus as in any one of claims 4 to 8 wherein said sample supply means (16) are further operable to flow said rinse therefrom and from said open sample container sample aspiration means (84) in the direction of aspirated sample flow therethrough, thereby flushing said sample supply (16) and open sample container sample aspiration means (84) to remove aspirated sample residue therefrom. Sampler apparatus as in any one of claims 4 to 9 wherein said open sample container sample aspiration means (84) comprise a probe (84), and wherein said rinse means (16) further comprise means operatively associated with said probe (84) and operable to rinse the exterior thereof to remove aspirated sample residue therefrom. Sampling method for supplying samples to sample analysis apparatus through use of sampler apparatus which comprise a closed tube sampler, an open tube sampler, and sampler rinse means, the steps of, selecting between said closed tube sampler and said open tube sampler for sample supply to said sample analysis apparatus, and selecting between said closed tube sampler and said open tube sampler for subsequent rinse by said sampler rinse means to remove sample residue therefrom. A method as in Claim 11 wherein said sampler apparatus include sample dividing means, and said method further comprises, the steps of, dividing said sample into separate sample quantities, supplying said separate sample quantities for independent sample quantity analysis, and rinsing said sample dividing means to remove sample residue therefrom. A method as in Claims 11 or 12, of supplying a sample from a closed sample container by the introduction of sample aspiration means thereinto, said method further comprising the steps of, equalizing the pressure in said closed sample container with ambient atmospheric pressure prior to sample aspiration therefrom, thereby preventing vacuum build-up in said closed sample container. A method as in Claims 11, 12 or 13, of supplying a sample from a closed sampler container by the introduction of sample aspiration means thereinto to withdraw said sample therefrom, and subsequently removing said sample aspiration means from said closed sample container, said method further comprising the steps of, flowing a rinse through said sample aspiration means against the direction of aspirated sample flow therethrough, thereby backflushing said sample aspiration means to remove aspirated sample residue therefrom, and subsequently flowing said rinse through said sample aspiration means in the direction of aspirated sample flow therethrough, thereby flushing said sample aspiration means to remove aspirated sample residue therefrom, and subsequently flowing ambient atmospheric air through said sample aspiration means, thereby air-drying the same to complete the cleansing thereof. A method as in either of claims 13 or 14 wherein said sample aspiration means comprise a sampling needle, and wherein the step of backflushing said sample needle with said rinse further comprises, the step of, flowing said rinse from the interior of said sampling needle around the exterior thereof, thereby removing aspirated sample residue from both the interior and exterior of said sampling needle. A method as in Claims 11 or 12 of supplying a sample from an open sample container by the introduction of sample aspiration means thereinto to withdraw said sample therefrom, and the subsequent removal of said sample aspiration means from said open sample container, the steps of, flowing a rinse through said sample aspiration means in the direction of aspirated sample flow therethrough thereby flushing said sample aspiration means to remove aspirated sample residue therefrom, and subsequently flowing a rinse through said sample aspiration means against the direction of aspirated sample flow therethrough thereby backflushing said sample aspiration means to remove aspirated sample residue therefrom. A method as in Claim 16 wherein said sample aspiration means comprise a probe further comprising, the steps of, subsequently flowing a rinse through said sample aspiration means in the direction of aspirated sample flow therethrough, thereby flushing said sample aspiration means to remove aspirated sample residue therefrom, and backflushing said probe comprise the flow of said rinse through the interior of said probe, and said method further includes, the steps of, rinsing the exterior of said probe to remove aspirated sample residue therefrom, and subsequently flowing ambient atmospheric air through said sample aspiration means and around the exterior of said probe, thereby air-drying the same to complete the cleansing thereof. A method as in Claims 16 or 17 wherein, the step of flowing said rinse through said sample aspiration means in the direction of aspirated sample flow therethrough to flush the same further comprises, the steps of, mixing ambient atmospheric air with said rinse for flow through said sample aspiration means, thereby increasing the effectiveness of the removal of aspirated sample residue therefrom.

Inventors: UFFENHEIMER, KENNETH F.
Applicants: TECHNICON INSTRUMENTS CORPORATION(A DELAWARE CORPORATION)
Application year: 1986
Main classification: G01N1
IPC codes: G01N35, G01N1