WO2002054085A1 - Dispositif, procede et produit de programme informatique pour acquisition automatique de donnees d'echantillonnage a fort rendement - Google Patents

Dispositif, procede et produit de programme informatique pour acquisition automatique de donnees d'echantillonnage a fort rendement Download PDF

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Publication number
WO2002054085A1
WO2002054085A1 PCT/US2002/000064 US0200064W WO02054085A1 WO 2002054085 A1 WO2002054085 A1 WO 2002054085A1 US 0200064 W US0200064 W US 0200064W WO 02054085 A1 WO02054085 A1 WO 02054085A1
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WIPO (PCT)
Prior art keywords
sample
port
instrument
analytical instrument
flushing
Prior art date
Application number
PCT/US2002/000064
Other languages
English (en)
Inventor
Erik D. Frederick
Gary M. Eichenbaum
Valery R. Polyakov
Hendrik M. Geysen
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Chemcodes, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Chemcodes, Inc. filed Critical Chemcodes, Inc.
Priority to US10/182,885 priority Critical patent/US20040014227A1/en
Publication of WO2002054085A1 publication Critical patent/WO2002054085A1/fr

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00584—Control arrangements for automatic analysers
    • G01N35/0092—Scheduling

Definitions

  • the present invention relates to apparatus, methods and computer program products for implementing and controlling improved high-throughput sampling and data acquisition. More particularly, the present invention relates to valve configurations and computer software for improving such sampling and data acquisition.
  • the present invention in one aspect achieves increased throughput by integrating sample delivery and data acquisition/analysis systems.
  • the present invention provides a computer software-controlled, robotic autosampling system for the rapid injection and flushing of samples into an analytical instrument such as, for example, a mass spectrometer.
  • the system comprises a valve assembly, a sample injection loop, appropriate tubing and pumps, a sampling probe such as an injection needle mounted on a robotic apparatus, and the analytical instrument.
  • the software consists of instrument controlling objects that function in a synchronous or asynchronous mode.
  • the software controls all aspects of the sampling and data acquisition processes implemented by the system, including sample take-up, sample injection, sampling needle rinsing, sample loop flushing, and sample injection flow rate.
  • the system provided by the invention enables an increase in sample throughput over conventional single-valve injection port-based systems.
  • the invention provides a novel valve assembly or system that is integrated with software to allow rapid sampling of multiple samples with minimal inter-sample delay and signal carryover.
  • the valve assembly is mounted to the robotic apparatus in close proximity to the sampling needle, so that the valve assembly is mounted within approximately 30 cm of any sample site of the system, and to limit dead volume to, in the non-limiting case of micro-sample delivery, less than approximately 35 ⁇ L.
  • a sample loop is connected to the valve assembly.
  • the valve assembly comprises a pair of multiport valves (each including, for example, six ports). Each valve is adjustable to at least two positions. By altering the combination of respective positions of the two valves, at least three positional modes can be realized by the valve assembly.
  • sample injection/needle rinse mode a sample injection flow path and a sampling needle rinsing flow path are defined. This mode is utilized to inject a sample contained in the sample loop, while simultaneously allowing the needle to be rinsed using an appropriate pump such as a syringe pump.
  • sample loop load/instrument flush mode a sampling loop loading flow path and an instrument flushing flow path are defined. This mode allows the sample loop to be loaded from the needle using the syringe pump, while simultaneously maintaining a continuous flow of solvent to the analytical instrument.
  • a sample loop flushing flow path as well as the instrument flushing flow path are defined.
  • This position allows sample injection to be interrupted without having to flush the entire sample into the analytical instrument.
  • the valve assembly can be switched to this position, and the remaining sample in the sample loop is diverted and flushed to waste and clean solvent is introduced into the analytical instrument at a constant rate.
  • the flow of a fluid (either a sample solution or clean solvent) to the analytical instrument is maintained.
  • the valve assembly comprises a single multiport valve that is adjustable to at least three positions for realization of the three functional modes.
  • valve assembly and associated autosampling system are provided in accordance with the present invention to address the needs of increased sample throughput into an analytical instrument.
  • the invention in at least one preferred embodiment satisfies the following conditions: a) Flow to the analytical instrument must not be interrupted between samples. b) The injection needle or probe employed by the system must be able to be rinsed during the injection of a sample. c) The system must be able to make a decision, based on predetermined parameters or algorithms, to dynamically abort a sample by flushing the sample to a waste line instead of through the analytical device. In one embodiment of the invention, a sample is taken up into an analytical instrument.
  • valve system ⁇ injection loop and pumped into the analytical instrument through the valve system. Based on a data-driven, software-controlled decision, the sample is either flushed to waste or sampled to completion. Additionally, placement of the valve system in close proximity to the sampling needle results in increased throughput by minimizing the time required for a sample to travel between the autosampling system and the analytical instrument, as well as a reduction in deadspace.
  • sample acquisition is performed by transferring a sample or at least an initial portion thereof into an analytical instrument.
  • the analytical instrument acquires data from the sample.
  • While the analytical instrument is acquiring data, one or more properties of the sample are measured or the status of the system or instrumentation is considered. A determination is made as to whether the sample or the associated system or instrumentation meets one or more decision criteria based on the one or more properties measured or on the status information obtained. In response to determining that the sample, system, or instrumentation has failed to meet any of the one or more decision criteria, the analytical instrument is caused to cease acquiring data from the sample or initial portion thereof. In response to determining that the sample, system, or instrumentation has met all of the one or more decision criteria, an additional portion of the sample is transferred into the analytical instrument and the analytical instrument acquires data from the additional portion.
  • a remaining portion of the sample can be prevented from being injected into the analytical instrument.
  • the remaining portion can be discarded or diverted away from the analytical instrument.
  • the remaining sample can also be transferred to a suitable apparatus, such as another analytical modality.
  • a sample is loaded into a sample reservoir such as a sample loop from a sample conduit that can include a sampling needle and associated plumbing. While the sample is being loaded an injection conduit is flushed.
  • the injection conduit can include an analytical instrument and/or plumbing necessary for transferring the sample into the analytical instrument. At least a portion of the sample is injecting through the injection conduit into an analytical instrument. While the sample is being injected, the sample conduit is flushed.
  • the sample reservoir is also flushed. While the sample reservoir is being flushed, the injection conduit is flushed.
  • the methods summarized hereinabove and described in more detail hereinbelow can be implemented by a computer program product comprising computer-executable instructions embodied in a computer-readable medium.
  • a valve assembly for use in sample data acquisition comprises a sample loop and a valve.
  • the valve comprises an aspiration/dispensing port, a sampling port, a waste port, a pump-side port, and an instrument-side port.
  • the valve is selectively adjustable to at least first, second and third positions.
  • the first position defines a sample injection flow path and a sampling probe flushing path
  • the second position defines a sample loop loading flow path and an instrument flushing flow path
  • the third position defines a sample loop flushing flow path.
  • the sample injection flow path is directed from the pump-side injection port, through the sample loop, and to the instrument-side injection port.
  • the sampling probe flushing path is directed from the aspiration/dispensing port to the sampling port.
  • the sample loop loading flow path is directed from the sampling port to the sample loop.
  • the instrument flushing flow path is directed from the pump-side injection port to the instrument-side injection port.
  • the sample loop flushing flow path is directed from the aspiration/dispensing port, through the sample loop, and to the waste port.
  • the valve assembly comprises a valve structure and a movable valve body.
  • the valve structure comprises the aspiration/dispensing port, the sampling port, the waste port, the pump-side port, and the instrument-side port.
  • the valve body comprises a plurality of internal fluid passages selectively communicating with one or more of the ports of the valve structure at the first, second and third positions.
  • the present invention provides embodiments of the valve assembly in dual-valve rotary, single-valve linear, and single-valve rotary configurations.
  • a sample analysis system comprises a robotic assembly, a sampling probe movably mounted to the robotic assembly, a sample loop, and a valve assembly mounted to the robotic assembly.
  • the valve assembly comprises an aspiration/dispensing port, a sampling port, a waste port, a pump-side port, and an instrument-side port.
  • the valve assembly is selectively adjustable to at least first, second and third positions. The first position defines a sample injection flow path and a sampling probe flushing path, the second position defines a sample loop loading flow path and an instrument flushing flow path, and the third position defines a sample loop flushing flow path.
  • a reversible pump such as a syringe pump fluidly communicates with the aspiration/dispensing port, a waste receptacle fluidly communicates with the waste port, an instrument pump fluidly communicates with the pump-side port, and an analytical instrument such as a mass spectrometer fluidly communicating with the instrument-side port.
  • a reversible pump such as a syringe pump fluidly communicates with the aspiration/dispensing port
  • a waste receptacle fluidly communicates with the waste port
  • an instrument pump fluidly communicates with the pump-side port
  • an analytical instrument such as a mass spectrometer fluidly communicating with the instrument-side port.
  • Figure 1 is a schematic view of an automated sampling and data acquisition system provided in accordance with the present invention
  • Figure 2 is an exploded perspective view of a conventional multiport valve suitable for use in certain embodiments of the invention
  • Figure 3A is a schematic diagram of a valve assembly provided in accordance with one embodiment of the present invention and positioned at a sample injection/needle rinsing mode;
  • Figure 3B is a schematic view of the valve assembly illustrated in Figure 3A and positioned at a sample loop load/instrument flush mode;
  • Figure 3C is a schematic view of the valve assembly illustrated in Figures 3A and 3B and positioned at a sample loop flush/instrument flush mode;
  • Figure 4 is a partially cutaway cross-sectional view of a valve assembly provided in accordance with another embodiment of the present invention
  • Figure 5A is a schematic diagram of the valve assembly illustrated in Figure 4 and positioned at a sample injection/needle rinsing mode
  • Figure 5B is a schematic diagram of the valve assembly illustrated in Figure 4 and positioned at a sample loop load/instrument flush mode;
  • Figure 5C is a schematic diagram of the valve assembly illustrated in
  • Figure 4 and positioned at a sample loop flush/instrument flush mode
  • Figure 6 is a cutaway cross-sectional view of a valve assembly provided in accordance with yet another embodiment of the present invention.
  • Figure 7A is a top plan view of an upper valve structure of the valve assembly illustrated in Figure 6;
  • Figure 7B is a bottom plan view of a lower valve structure of the valve assembly illustrated in Figure 6;
  • Figure 7C is a perspective view of a valve body of the valve assembly illustrated in Figure 6;
  • Figure 8A is a schematic diagram of the valve assembly illustrated in Figure 6 and positioned at a sample injection/needle rinsing mode;
  • Figure 8B is a schematic diagram of the valve assembly illustrated in Figure 6 and positioned at a sample loop load/instrument flush mode;
  • Figure 8C is a schematic diagram of the valve assembly illustrated in Figure 6 and positioned at a sample loop flush/instrument flush mode;
  • Figure 9 is a schematic diagram illustrating an exemplary operational control environment for the system illustrated in Figure 1 ;
  • Figures 10A and 10B are block diagrams illustrating a sampling and data acquisition process carried out by the present invention.
  • Figure 11 is a block diagram illustrating a data-driven decisional process executed by computer software in accordance with the present invention.
  • Figure 12 is a plot of intensity versus time illustrating the rapid data acquisition of multiple samples in accordance with the present invention.
  • Figure 13 is a plot of intensity versus time illustrating the throughput performance achieved by the present invention in comparison to the performance achieved by a conventional sampling and data acquisition system.
  • valve assembly and "valve system” are taken to mean a valve unit that contains a single valve or manifold structure or a plurality of valves or manifold structures.
  • cleaning and “flushing” are used interchangeably to mean replacing a plug or volume of fluid with clean solvent and/or cleaning the inner walls of a liquid conduit by carrying away residual contaminants.
  • Sampling system 10 comprises a liquid handling apparatus, generally designated 20; a valve assembly VA; one or more solvent reservoirs 51; a high-pressure pump unit P 2 ; an analytical instrument Al; and an electronic control unit or computer 100 with computer software 112 (see Figure 9).
  • Liquid handling apparatus 20 is generally employed to perform sample preparation and liquid handling procedures, including the sequential injections of samples into analytical instrument Al.
  • the operations of liquid handling apparatus 20 are programmable by means of written, executable software instructions for these purposes.
  • liquid handling apparatus 20 comprises a main structural frame (a portion of which is designated 23) on which various operative components are supported.
  • main frame 23 Preferably attached to or supported by main frame 23 is a rack assembly 25 on which a variety of different types of racks or plates R., - R n can be removably mounted.
  • racks R - R n are usually constructed of aluminum, polypropylene, or quartz, depending on the particular application or sample composition contemplated.
  • Racks R., - R n can be plates that include respective arrays of wells for containing sample solutions, or can include an array of holes for holding vials, test tubes, cuvettes or other types of vessels that in turn contain sample solutions.
  • each rack R., - R n could constitute a conventional 96-well microtitre plate, thereby enabling liquid handling apparatus 20 to process a large number of different samples.
  • liquid handling apparatus 20 could be an originally constructed apparatus, or could be provided as or adapted from a commercially available apparatus.
  • a suitable commercially available apparatus is a GilsonTM Model 215 Liquid HandlerTM apparatus available from Gilson, Inc., Middleton, Wisconsin.
  • Such an apparatus, as well as other similar liquid handling apparatuses conventionally provides an injection port for direct injection of samples into an HPLC unit or an injection module for injection of samples into a mass spectrometry unit.
  • the standard injection port or module is not required in the present invention.
  • Robotic assembly 30 includes a sample aspiration and dispensing device, which preferably is provided as a sampling probe or needle SN. While conventional needles typically have a 0.03-inch bore, it is preferable that sampling needle SN used in the present invention have a 0.015-inch bore to further minimize deadspace and reduce the volume of the sample in the sample vessels required for filling a sample loop or other suitable sample reservoir. The tip of sampling needle SN can be sharpened if desired to enable penetration through the septum of a sample-holding container that is sealed in such manner.
  • Sampling needle SN is linked to a vertical arm 33 of robotic assembly 30 by a suitable needle mounting unit or carriage unit 35.
  • Sampling needle SN and its carriage unit 35 slide along a vertical track 33A of vertical arm 33 along a vertical direction indicated by vertical axis Z.
  • Vertical arm 33 is linked through a suitable linkage 39 to a horizontal arm 41.
  • Vertical arm 33 and its linkage 39 slide along a horizontal track (not shown) along a horizontal direction running into and out of the sheet of Figure 1 , as indicated by the point of horizontal axis Y.
  • Horizontal arm 41 is linked to main frame 23 and slides along a horizontal track 23A along a horizontal direction indicated by horizontal axis X.
  • robotic assembly 30 can be programmed to move sampling needle SN to and from various sites of liquid handling apparatus 20, including the various wells or vessels disposed on racks R., - R n as well as a rinsing station or waste receptacle W ordinarily integrally provided in some form with liquid handling apparatus 20.
  • Liquid handling apparatus 20 further includes a pump P , which can be integrated with liquid handling apparatus 20 or provided as a separate module.
  • pump P 1 is a syringe pump or other conventionally designed pump that is capable of reversible or two-way flow (i.e., for both aspiration and dispensing), and to which inlet and outlet liquid transfer lines L, and L 2 , respectively, are connected.
  • Liquid transfer lines L, and L 2 are usually constructed of PTFE tubing or a similarly chemically inert and flexible material.
  • Inlet liquid transfer line L communicates with one or more solvent reservoirs 51.
  • Outlet liquid transfer line L 2 conventionally communicates directly with sampling needle SN, but in the present invention communicates with valve assembly VA as described in more detail hereinbelow.
  • Valve assembly VA is configured to enable the advantageous methods of the present invention as described in more detail hereinbelow.
  • valve assembly VA comprises two multiport valves V, and V 2 as specifically shown in Figure 1.
  • valve assembly VA comprises a single multiport valve in accordance with other embodiments of the invention described hereinbelow.
  • Each valve V, and V 2 provided by valve assembly VA can be of conventional design.
  • a typical valve generally designated 60, includes a rotary valve body 62 and a stationary structure such as a disk 64.
  • Valve body 62 contains a network of internal passages 66A, 66B and 66C, and disk 64 has a plurality of ports 68A - 68F that communicate with one or more of internal passages 66A - 66C.
  • Transfer tubing lines (not shown in Figure 2) are connected to one or more of ports 68A - 68F to enable fluid communication between valve 60 and the fluid circuit in which valve 60 operates along desired flow paths.
  • Other ports 68A - 68F may be plugged to prevent siphoning and entry of air into the system.
  • Valve body 62 can be rotated in an indexing fashion by a stepper motor 70 and suitable coupling and transmission means to re-align ports 68A - 68F with at least some of internal passages 66A - 66C and thus switch or alter the course or courses of one or more flow paths associated with the fluid circuit.
  • a multiport valve that is suitable for use as a valve of valve assembly VA is the RheodyneTM Model 7010 valve incorporated into the GilsonTM Model 819 Injection ModuleTM apparatus available from Gilson, Inc., Middleton, Wisconsin.
  • FIG. 1 illustrates a preferred embodiment of the fluid circuit arrangement associated with sampling system 10 in accordance with the invention.
  • syringe pump P 1 communicates with solvent reservoir 51 through liquid transfer line L,, and with valve V, through liquid transfer line L 2 .
  • Valve V communicates with high-pressure pump P 2 through a liquid transfer line L 3 , and with analytical instrument Al through a liquid transfer line L 4 .
  • Valve V also includes a sample loop SL, the use and operation of which are generally known in the art, or some other type of sample reservoir suitable for containing a precise volume of a liquid-phase containing substance such as a solvent or a sample carried by a mobile phase or dissolved in a solvent.
  • Valve V 2 communicates with waste receptacle W through a liquid transfer line L 5 , and with sampling needle SN through a liquid transfer line L 6 . Finally, valves V, and V 2 communicate with each other through a fluid transfer line L 7 .
  • Valve assembly VA is mounted directly to robotic assembly 30 so as to minimize the length of fluid passages and hence the total dead volume. Preferably, valve assembly VA is mounted to vertical arm 33 of robotic assembly 30 through a suitable mounting bracket or bracket assembly 55.
  • the dead volume is defined by the volume of sampling needle SN, the volume of liquid transfer line L 6 , the volume of liquid transfer line L 7 and the internal volumes of V, and V 2 .
  • valves V, and V 2 are disposed within approximately 30 cm of any sample well or vessel of racks R 1 - R n at any given time during operation of sampling system 10.
  • High-pressure pump P 2 can be any pump suitable for moving fluid at pressures normally used for injecting samples into analytical instruments.
  • high-pressure pump P 2 can operate at different flow rates and/or pressures.
  • high-pressure pump P 2 can be the type of pump conventionally used to inject samples into an HPLC instrument.
  • a suitable commercially available pump is a GilsonTM Model 307 isocratic pump available from Gilson, Inc., Middleton, Wisconsin.
  • High-pressure pump P 2 communicates with solvent reservoir 51 through a liquid transfer line L 8 , or alternatively could communicate with a separate solvent reservoir (not shown).
  • Analytical instrument Al can be any instrument used in the art to analyze samples.
  • analytical instrument Al constitutes a mass spectrometer, although the invention is not limited to such an instrument.
  • other types of instruments suitable for use in connection with the invention include those designed to carry out optical spectrochemical analysis in the UV, visible, and IR spectra (e.g., spectroscopy and spectrophotometry).
  • the particular analytical instrument Al used in the present invention is not limited by any sample size restrictions.
  • the advantages provided by the invention can be realized using an analytical instrument Al capable of either macro analysis (0.1 g or greater sample weight), semimicro or meso analysis (0.01 to 0.1 g), micro analysis (10 "4 to 10 "2 g), ultramicro analysis (10 "4 g or less), or ultra-trace analysis.
  • Analytical instrument Al could be capable of performing qualitative and/or quantitative analyses. Analytical instrument Al could be capable of performing multiple- species analyses in either a sequential, simultaneous, or parallel manner. In addition, analyzing instrument Al could comprise more than one analytical modality (e.g., two mass spectrometers, a mass spectrometer and a fraction collector, and so on).
  • analytical modality e.g., two mass spectrometers, a mass spectrometer and a fraction collector, and so on.
  • Figures 3A- 3C illustrate three modes attainable by valve assembly VA when valve assembly VA is provided in the two-valve configuration. Specifically, Figure 3A illustrates a sample injection/needle rinse mode, Figure 3B illustrates a sample loop load/instrument flush mode, and Figure 3C illustrates a sample loop flush/instrument flush mode. These modes are attained by selectively adjusting the respective rotary valve bodies of first and second valves V, and V 2 . The adjustments have the effect of selecting which pairs of ports on each valve V, and V 2 become fluidly interconnected by the internal passages that rotate with their respective valve bodies, as well as which components of sampling system 10 are actively associated with the flow paths defined by the three modes.
  • valve V includes ports A - F and adjustable internal passages a - c
  • valve V 2 includes ports G - L and adjustable internal passages d - f.
  • the ends of sample loop SL are fluidly connected at ports A and D, respectively, of valve V,.
  • Liquid transfer line L 7 fluidly interconnects valves V, and V 2 at port C of valve V, and port K of valve V 2 .
  • Liquid transfer line L 2 fluidly interconnects syringe pump P n of liquid handling apparatus 20 with valve V, at port B.
  • Liquid transfer line L 3 fluidly interconnects high-pressure pump P 2 with valve V, at port F.
  • Liquid transfer line L 4 fluidly interconnects analytical instrument Al with valve V, at port E.
  • Liquid transfer line L 6 fluidly interconnects sampling needle SN (or a suitable, alternative sample source) with valve V 2 at port L.
  • liquid transfer line L s fluidly interconnects waste receptacle W with valve V 2 at port J.
  • valves V, and V 2 are positioned at the sample injection/needle rinse mode. This mode enables a sample contained in sample loop SL to be injected into analytical instrument Al and, simultaneously, sampling needle SN to be rinsed with a suitable solvent.
  • Valve V is positioned such that internal passage a fluidly interconnects port B and port C, internal passage b fluidly interconnects port D and port E, and internal passage c fluidly interconnects port F and port A.
  • Valve V 2 is positioned such that internal passage f fluidly interconnects port L and port K.
  • valves V, and V 2 are positioned to define two flow paths: a sample injection flow path P 2 -» L 3 - F - c - A - SL - D - b -> E -> L 4 - Al; and a sampling needle rinsing flow path P., - L 2 - B -> a - C - L 7 ⁇ K -> f ⁇ L ⁇ L 6 ⁇ SN.
  • a sample previously loaded into sample loop SL is injected into analytical instrument Al by moving through port D, internal passage b, port E, and liquid transfer line L 4 .
  • the sample moves and is thus injected into analytical instrument Al under the influence of high- pressure pump P 2 , which creates fluid pressure in transfer line L 3 , port F, internal passage c, and port A.
  • syringe pump P. draws solvent from solvent reservoir 51 (see Figure 1 ) through liquid transfer line L,, and pushes the solvent through liquid transfer line L 2 , port B, internal passage a, port C, liquid transfer line L 7 , port K, internal passage f, port L, liquid transfer line L 6 , and sampling needle SN.
  • a control signal be sent to robot apparatus 30 (see Figure 1 ) to position sampling needle SN at an appropriate waste receptacle, such as waste receptacle W, or a rinsing station for collection of the used solvent.
  • valves V, and V 2 are positioned at the sample loop load/instrument flush mode. This mode enables a sample of precise volume to be loaded into sample loop SL and, simultaneously, analytical instrument Al to be flushed with a clean solvent.
  • Valve V has been rotated, and is now positioned such that internal passage a fluidly interconnects port C and port D, internal passage b fluidly interconnects port E and port F, and internal passage c fluidly interconnects port C and port B.
  • the position of valve V 2 is maintained at the position shown in Figure 3A, such that internal passage f fluidly interconnects port K and port L.
  • valves V, and V 2 are positioned to define two flow paths: a sample loading flow path SN - L 6 -» L -> f -> K - ⁇ L 7 -» C - ⁇ a ⁇ D - SL -> A - c - B -> L 2 -> P.,; and an instrument flushing flow path P 2 - L 3 - F ⁇ b -» E - L 4 ⁇ Al.
  • sample loading flow path a sample that has been drawn into sampling needle SN moves through transfer line L 6 , port L, internal passage f, port K, transfer line L 7 , port C, internal passage a, port D, and into sample loop SL.
  • the sample is pulled by the vacuum induced by syringe pump P ⁇ through transfer line L 2 , port B, internal passage c, and port A.
  • the particular sample loaded in sample loop SL is selected by sending appropriate control signals to liquid handling apparatus 20 (see Figure 1).
  • robotic assembly 30 is caused to move sampling needle SN into position over a selected vessel of the array of vessels contained on a selected one of racks R 1 - R n , after which time sampling needle SN is lowered into the selected vessel and syringe pump P., activated to cause the selected sample (or an aliquot thereof) to be aspirated into sampling needle SN.
  • solvent is circulated by high-pressure pump P 2 into analytical instrument Al through transfer line L 3 , port F, internal passage b, port E, and transfer line L 4 .
  • Analytical instrument Al is considered to be completely flushed when the only artifacts observed by analytical instrument Al are those characterizing the solvent used.
  • analytical instrument Al is typically equipped with means for collecting all substances it receives.
  • an air handling system takes away the vapors produced by or sent through the mass spectrometer.
  • valves V, and V 2 are positioned at the sample loop flush/instrument flush mode. This mode enables sample loop SL to be flushed with a suitable solvent and, simultaneously, analytical instrument Al to be flushed with a suitable solvent.
  • the position of valve V is maintained at the position shown in Figure 3B, such that internal passage a fluidly interconnects port C and port D, internal passage b fluidly interconnects port E and port F, and internal passage c fluidly interconnects port A and port B.
  • Valve V 2 has been rotated, and is now positioned such that internal passage d fluidly interconnects port J and port K.
  • valves V, and V 2 are positioned to define two flow paths: a sample loop flushing flow path P., ⁇ L 2 ⁇ B -> c ⁇ A -> SL ⁇ D - a ⁇ C ⁇ L 7 ⁇ K - d - J - L s -> W; and the instrument flushing flow path P 2 - L 3 - F - b -> E -> L 4 -> Al described hereinabove with reference to Figure 3B.
  • syringe pump P. is activated to draw solvent from solvent reservoir 51 through liquid transfer line L, (see Figure 1) and to push the solvent through transfer line L 2 , port B, internal passage c, and port A, thereby causing a sample residing in sample loop SL to be pushed through port D, internal passage a, . port C, transfer line L 7 , port K, internal passage d, port J, transfer line L s , and into waste receptacle W.
  • the instrument flushing flow path can continue to be used to flush analytical instrument Al.
  • valve assembly VA is capable of loading sample loop SL while flushing analytical instrument Al, injecting the sample from sample loop SL while rinsing sampling needle SN, and flushing the remaining sample in sample loop SL to waste while flushing clean solvent into analytical instrument Al. Moreover, at each state attained by valve assembly VA, some form of fluid, whether containing a sample or a rinsing medium, is being circulated through analytical instrument Al.
  • the operation of valve assembly VA and the rapid switching of valve assembly VA among its three modes or states significantly increases the throughput of sampling data acquisition processes as compared to, for example, conventional injection port-based systems due to the decreased inter-sample delay time needed to reach acceptable carryover requirements and the time savings realized by eliminating the injection port.
  • Valve assembly VA' is a linear valve design in which a valve body 81 slides within a stationary housing structure 83.
  • Valve body 81 is actuated by a suitable actuator (not shown, but could be, e.g., a solenoid, pneumatic cylinder, hydraulic cylinder, motor, worm drive, or the like) through a suitable arm or other linkage mechanism 85.
  • Valve body 81 can be actuated by a reciprocating, double-acting actuator of known design, or alternatively could be actuated in alternative directions respectively by two oppositely disposed actuators (in which case an additional, oppositely disposed linkage mechanism 85 would be required).
  • Housing structure 83 has an upper portion 83A and a lower portion 83B.
  • Valve assembly VA' has eight ports A - H.
  • Upper portion 83A of housing structure 83 includes ports A, B and C, and lower portion 83B includes ports D, E and F.
  • Valve body 81 includes ports G and H, which preferably are internally disposed with respect to housing structure 83.
  • Valve body 81 also includes six internal passages a - f. The centermost passages, internal passages c and d, are disposed in opposing, linear alignment with each other and terminate at ports G and H, respectively.
  • Sample loop SL is fluidly connected to ports G and H. Sample loop SL moves with valve body 81 and preferably is disposed internally with respect to housing structure 83 but could be located externally, connecting to ports G and H.
  • valve body 81 In the position of valve body 81 shown in Figure 4, internal passage b fluidly interconnects ports A and D, internal passage c fluidly interconnects ports B and G, internal passage d fluidly interconnects ports H and E, and internal passage e fluidly interconnects ports C and F. Additionally, internal passages a and f are effectively plugged at their respective openings by upper and lower portions 83A and 83B of housing structure 83. It can be seen, however, that as valve body 81 is selectively and controllably actuated to the left and to the right, different internal passages a - f are brought into fluid communication with different ports A - F in order to alter the fluid circuit with which valve assembly VA' is associated. As indicated in Figure 4, internal passage c is always fluidly associated with port G and internal passage d is likewise always fluidly associated with port H.
  • Figures 5A- 5C illustrate the three modes attainable by valve assembly VA' when valve assembly VA' is provided in the linear valve configuration illustrated in Figure 4. Specifically, Figure 5A illustrates the sample injection/needle rinse mode, Figure 5B illustrates the sample loop load/instrument flush mode, and Figure 5C illustrates the sample loop flush/instrument flush mode. These modes are attained by selectively adjusting valve body 81 with respect to housing structure 83 (see Figure 4). The adjustments have the effect of selecting which ports A ⁇ H become fluidly interconnected by internal passages a - f, as well as which components of sampling system 10 are actively associated with the flow paths defined by the three modes. In the present invention, the actuating movements required to effect the valve adjustments are initiated and controlled by drive signals supplied from electronic control unit 100 (see Figure 9) to the actuator connected to linkage mechanism 85 (see Figure 4).
  • fluid connections are made at ports A - H of valve assembly VA' from various components of sampling system 10 as in the case of valve assembly VA illustrated in Figures 3A - 3C.
  • High-pressure pump P 2 of liquid handling apparatus 20 is connected to both ports A and B by dividing the flow through liquid transfer line L 3 into two separate flow paths respectively directed to ports A and B, using a flow splitter or tee connection and two additional liquid transfer lines (not shown).
  • two separate high-pressure pumps P 2 (or a high-pressure pump and a syringe pump) and corresponding liquid transfer lines L 3 could be provided for transporting solvent through ports A and B, respectively.
  • Liquid transfer line L 2 fluidly interconnects syringe pump with valve assembly VA' at port C.
  • Liquid transfer line L 5 fluidly interconnects waste receptacle W with valve assembly VA' at port D.
  • Liquid transfer line L 4 fluidly interconnects analytical instrument Al with valve assembly VA' at port E.
  • Liquid transfer line L 6 fluidly interconnects sampling needle SN or other sample source with valve assembly VA' at port F.
  • Sample loop SL fluidly communicates with valve assembly VA' at ports G and H.
  • valve body 81 is positioned at the sample injection/needle rinse mode. Valve body 81 is positioned such that internal passage a is plugged, internal passage b fluidly interconnects ports A and D, internal passage c fluidly interconnects ports B and G, internal passage d fluidly interconnects ports H and E, internal passage e fluidly interconnects ports C and F, and internal passage f is plugged.
  • valve body 81 is positioned to define two flow paths: a sample injection flow path P 2 - L 3 -> B - c -> G - SL -> H -> d -> E -> L 4 - Al; and a sampling needle rinsing flow path P., - L 2 -> C - e - F - L 6 - SN.
  • a sample previously loaded into sample loop SL is injected into analytical instrument Al by moving through port H, internal passage d, port E, and liquid transfer line L 4 .
  • syringe pump P draws solvent from solvent reservoir 51 through liquid transfer line L, (see Figure 1), and pushes the solvent through liquid transfer line L 2 , port C, internal passage e, port F, liquid transfer line L 6 , and sampling needle SN.
  • a control signal be sent to robot apparatus 30 (see Figure 1 ) to position sampling needle SN at an appropriate waste receptacle, such as waste receptacle W, or a rinsing station for collection of the used solvent.
  • valve body 81 is positioned at the sample loop load/instrument flush mode. Valve body 81 is positioned such that internal passage a fluidly interconnects ports A and D, internal passage b fluidly interconnects ports B and E, internal passage c fluidly interconnects ports C and G, internal passage d fluidly interconnects ports H and F, and internal passages e and f are plugged.
  • valve body 81 In the sample loop load/instrument flush mode, valve body 81 is positioned to define two flow paths: a sample loading flow path SN ⁇ » L 6 - F ⁇ d -» H - SL - G -> c - C - L 2 -> P,; and an instrument flushing flow path P 2 - L 3 - B - b -> E - L 4 - Al.
  • a sample that has been drawn into sampling needle SN moves through transfer line L 6 , port F, internal passage d, port H, and into sample loop SL.
  • the sample is pulled by the vacuum induced by syringe pump P through transfer line L 2 , port C, internal passage c, and port G.
  • sample loaded in sample loop SL is selected by sending appropriate control signals to liquid handling apparatus 20 and robotic assembly 30 (see Figure 1) as described hereinabove.
  • solvent is circulated by high-pressure pump P 2 into analytical instrument Al through transfer line L 3 , port B, internal passage b, port E, and transfer line L 4 .
  • valve body 81 is positioned at the sample loop flush/instrument flush mode. Valve body 81 is positioned such that internal passages a and b are plugged, internal passage c fluidly interconnects ports A and G, internal passage d fluidly interconnects ports H and D, internal passage e fluidly interconnects ports B and E, and internal passage f fluidly interconnects ports C and F.
  • valve body 81 In the sample loop flush/instrument flush mode, valve body 81 is positioned to define two flow paths: a sample loop flushing flow path P 2 - L 3 - A - c - G -> SL - H - d - D - L 5 - W; and another instrument flushing flow path P 2 - L 3 - B -> e - E -> L 4 - Al.
  • high-pressure pump P 2 is activated to draw solvent from solvent reservoir 51 through liquid transfer line L 8 (see Figure 1) and to push the solvent through transfer line L 3 , port A, internal passage c, and port G, thereby causing a sample residing in sample loop SL to be pushed through port H, internal passage d, port D, transfer line L 5 , and into waste receptacle W.
  • the instrument flushing flow path can be used to flush analytical instrument Al.
  • Valve assembly VA is a rotary design in which a valve body 91 rotates in relation to a stationary upper valve structure 93A and a stationary lower valve structure 93B.
  • Valve body 91 is preferably cylindrical, and upper and lower valve structures 93Aand 93B are preferably disk-shaped.
  • Valve body 91 is actuated by a suitable actuator (not shown, but could be, e.g., a solenoid, pneumatic cylinder, hydraulic cylinder, motor, or the like) through a suitable arm or other linkage mechanism (not shown).
  • the linkage mechanism could be, for example, an endless member such as a belt that operatively engages the outer lateral surface of valve body 91, or could be a rotatable shaft that is connected to valve body 91 through a bore (not shown) in upper valve structure 93A or lower valve structure 93B.
  • Valve assembly VA" has eight ports A - H.
  • Upper valve structure 93A includes ports A, B and C
  • lower valve structure 93B includes ports D, E and F.
  • Valve body 91 includes ports G and H, which preferably are internally disposed with respect to a structure (not shown) that houses valve body 91.
  • Valve body 91 also includes four internal passages a - d.
  • Internal passages b and c are disposed in opposing, linear alignment with each other and terminate at ports G and H, respectively.
  • Sample loop SL is fluidly connected to ports G and H and rotates with valve body 91.
  • valve body 91 is selectively and controllably actuated to rotate with respect to upper and lower valve structures 93A and 93B, different internal passages a - d are brought into fluid communication with different ports A - F in order to alter the fluid circuit with which valve assembly VA" is associated.
  • internal passage b is always fluidly associated with port G and internal passage c is likewise always fluidly associated with port H.
  • Figures 8A- 8C illustrate the three modes attainable by valve assembly VA" when valve assembly VA" is provided in the rotary valve configuration illustrated in Figures 6 and 7A - 7C.
  • Figure 8A illustrates the sample injection/needle rinse mode
  • Figure 8B illustrates the sample loop load/instrument flush mode
  • Figure 8C illustrates the sample loop flush/instrument flush mode.
  • These modes are attained by selectively adjusting valve body 91 with respect to upper and lower valve structures 93A and 93B (see Figures 6 and 7A - 7C).
  • the adjustments have the effect of selecting which ports A - H become fluidly interconnected by internal passages a -- d, as well as which components of sampling system 10 are actively associated with the flow paths defined by the three modes.
  • the actuating movements required to effect the valve adjustments are initiated and controlled by drive signals supplied from electronic control unit 100 (see Figure 9) to the actuator associated with valve assembly VA".
  • valve assembly VA the fluid connections made at ports A - H of valve assembly VA" are roughly analogous to those illustrated in Figures 5A - 5C regarding valve assembly VA'.
  • High- pressure pump P 2 of liquid handling apparatus 20 is connected to both ports A and B by dividing the flow through liquid transfer line L 3 into two separate flow paths respectively directed to ports A and B, using a flow splitter or tee connection and two additional liquid transfer lines (not shown).
  • two separate high-pressure pumps P 2 (or syringe pumps) and corresponding liquid transfer lines L 3 could be provided for transporting solvent through ports A and B.
  • Liquid transfer line L 2 fluidly interconnects syringe pump P., with valve assembly VA" at port C.
  • Liquid transfer line L 5 fluidly interconnects waste receptacle W with valve assembly VA" at port D.
  • Liquid transfer line L 4 fluidly interconnects analytical instrument Al with valve assembly VA" at port E.
  • Liquid transfer line L 6 fluidly interconnects sampling needle SN with valve assembly VA" at port F.
  • Sample loop SL fluidly communicates with valve assembly VA" at ports G and H.
  • valve body 91 is positioned at the sample injection/needle rinse mode. Valve body 91 is positioned such that internal passage a fluidly interconnects ports A and D, internal passage b fluidly interconnects ports B and G, internal passage c fluidly interconnects ports H and E, and internal passage d fluidly interconnects ports C and F.
  • valve body 91 In the sample injection/needle rinse mode, valve body 91 is positioned to define two flow paths: a sample injection flow path P 2 - ⁇ L 3 - ⁇ B - b -> G - SL - H - c - E - L 4 - Al; and a sampling needle rinsing flow path P 1 ⁇ L 2 -> C - d -> F - L 6 -> SN.
  • a sample previously loaded into sample loop SL is injected into analytical instrument Al by moving through port H, internal passage c, port E, and liquid transfer line L 4 .
  • syringe pump P ⁇ draws solvent from solvent reservoir 51 through liquid transfer line L, (see Figure 1), and pushes the solvent through liquid transfer line L 2 , port C, internal passage d, port F, liquid transfer line L 6 , and sampling needle SN.
  • a control signal be sent to robot apparatus 30 (see Figure 1) to position sampling needle SN at an appropriate waste receptacle, such as waste receptacle W, or a rinsing station for collection of the used solvent.
  • valve body 91 is positioned at the sample loop load/instrument flush mode. Valve body 91 has been rotated, and is now positioned such that internal passage a fluidly interconnects ports B and E, internal passage b fluidly interconnects ports C and G, internal passage c fluidly interconnects ports H and port F, and internal passage d fluidly interconnects ports A and D.
  • valve body 91 In the sample loop load/instrument flush mode, valve body 91 is positioned to define two flow paths: a sample loading flow path SN -> L « -> F -> c - ⁇ H - ⁇ SL - G - ⁇ b -> C - ⁇ L 2 -> P.,; and an instrument flushing flow path P 2 -> L 3 -> B -> a -> E -> L 4 -> Al.
  • a sample that has been drawn into sampling needle SN moves through transfer line L 6 , port F, internal passage c, port H, and into sample loop SL.
  • the sample is pulled by the vacuum induced by syringe pump P., through transfer line L 2 , port C, internal passage b, and port G.
  • sample loaded in sample loop SL is selected by sending appropriate control signals to liquid handling apparatus 20 and robotic assembly 30 (see Figure 1) as described hereinabove.
  • solvent is circulated by high-pressure pump P 2 into analytical instrument Al through transfer line L 3 , port B, internal passage a, port E, and transfer line L 4 .
  • valve body 91 is positioned at the sample loop flush/instrument flush mode. Valve body 91 has again been rotated, and is now positioned such that internal passage a fluidly interconnects ports C and F, internal passage b fluidly interconnects ports A and G, internal passage c fluidly interconnects ports H and D, and internal passage d fluidly interconnects ports B and E.
  • valve body 91 In the sample loop flush/instrument flush mode, valve body 91 is positioned to define two flow paths: a sample loop flushing flow path P 2 -» L 3 -» A - ⁇ b -» G ⁇ » SL -» H -» c ⁇ » D ⁇ » L s ⁇ » W; and another instrument flushing flow path P 2 - L 3 -> B - d -> E - L 4 - Al.
  • high-pressure pump P 2 is activated to draw solvent from solvent reservoir 51 through liquid transfer line L 8 (see Figure 1) and to push the solvent through transfer line L 2 , port A, internal passage b, and port G, thereby causing a sample residing in sample loop SL to be pushed through port H, internal passage c, port D, transfer line L 5 , and into waste receptacle W.
  • the instrument flushing flow path can be used to flush analytical instrument Al.
  • FIG 9 is a schematic diagram illustrating an exemplary operational control environment for the invention.
  • the environment generally comprises an electronic control unit such as a computer 100 that can send output signals to and receive input signals from liquid handling apparatus 20 (including the operational components of robotic assembly 30, syringe pump P., and high- pressure pump P 2 ), valve assembly VA, and analytical instrument Al over suitable electronic transmission lines 102, 104 and 106, respectively (or, alternatively, by wireless means).
  • liquid handling apparatus 20 including the operational components of robotic assembly 30, syringe pump P., and high- pressure pump P 2
  • valve assembly VA and analytical instrument Al over suitable electronic transmission lines 102, 104 and 106, respectively (or, alternatively, by wireless means).
  • Computer 100 can be provided as a commercially available personal computer with a standard operating system such as WINDOWS ® , UNIX ® , LINUX ® , or the like. In addition, computer 100 preferably communicates over an electronic transmission line 108 with a peripheral user interface 110 to enable the user to input commands (e.g., by way of a keyboard) and to view output (e.g., by way of a monitor). Computer 100 processes data and instructions provided by control software 112. Control software 112 can comprise a single set of instructions, or could comprise a plurality of suitably interfaced and compatible modules or programs. For example, control software 112 could comprise several discrete objects each consisting of function-specific routines and data structures. Non-limiting examples of such objects include robotic drive, valve actuation, pump actuation, and analytic instrument control objects.
  • FIGS 10A and 10B illustrate an example of a sampling and data acquisition process performed by sampling system 10 under the control of control software 112.
  • block 201 designates the start of the sampling and data acquisition process.
  • high-pressure pump P 2 is set to a baseline flow rate.
  • signals are sent by control software 112 to liquid handling apparatus 20 and valve assembly VA to initiate the sample loop flush/instrument flush mode.
  • high-pressure pump P 2 is set to a high flow rate suitable for flushing the liquid lines, ports and passages that are fluidly associated with analytical instrument Al and valve assembly VA.
  • valve assembly VA has been set to the position illustrated in Figure 3C at which the instrument flushing flow path is defined, and solvent flows to analytical instrument Al.
  • solvent continues to flow to analytical instrument Al for a predetermined time so as to minimize carryover.
  • high-pressure pump P 2 is reset to the baseline flow rate.
  • solvent continues to flow through the instrument flushing flow path while control software 112 waits for analytical instrument Al to be readied for the ensuing data acquisition of a sample.
  • valve assembly VA has been set to the position illustrated in Figure 3C at which the sample loop flushing flow path is defined (which is the same position at which the instrument flushing flow path is defined).
  • syringe pump P. is activated to aspirate solvent from solvent reservoir 51 into the sample loop flushing flow path.
  • solvent flowing through the sample loop flushing flow path is dispensed through sample loop SL and into waste receptacle W under the influence of syringe pump P.,.
  • valve assembly VA is set to the sample injection/needle rinse mode illustrated in Figure 3A.
  • syringe pump P is activated to aspirate solvent from solvent reservoir 51 into the sampling needle rinsing flow path.
  • solvent flowing through the sampling needle rinsing flow path is dispensed through sample needle SN under the influence of syringe pump P r
  • control software 112 waits for the operations represented by blocks 205 - 213 and 215 -- 225 to complete before proceeding to the following sample loading and sample injection procedures.
  • control software 112 sends a signal to robotic assembly 30 to transport sampling needle SN to predetermined coordinates that define a selected rack R., - R n and a specific sample vessel selected from the array of sample vessels located on the rack R., - R n .
  • robotic assembly 30 causes the tip of sampling needle SN to enter the selected sample vessel.
  • valve assembly VA is set to the position illustrated in Figure 3B at which the sample loop loading flow path is defined.
  • syringe pump P 1 is activated to aspirate the particular sample contained in the selected sample vessel into sampling needle SN and the sample is transferred through the sample loop loading flow path into sample. loop SL.
  • valve assembly VA is set to the position illustrated in Figure 3A at which the sample injection path is defined.
  • Control software 112 sends a signal to high-pressure pump P 2 to begin injection of the sample contained in sample loop SL into analytical instrument Al.
  • control software 112 initiates a count based on flow rate to determine a time at which sample loop SL has been partially emptied.
  • control software 112 waits while the respective operations of liquid handling apparatus 20, valve assembly VA, and analyzing instrument Al represented by blocks 231 - 239 complete in preparation for data acquisition by analytical instrument Al.
  • control software 112 sends a signal to analytical instrument Al to initiate data acquisition from the sample.
  • control software 112 sets the flow rate of high-pressure pump P 2 to an intermediate level to accelerate the sample into analytical instrument Al.
  • control software 112 waits for the sample to arrive at analytical instrument Al and then, at block 249, backs the flow rate of high-pressure pump P 2 down to the baseline level while the sample is flowing into analytical instrument Al. As indicated in Figures 10A and 10B, this entire sampling and data acquisition cycle is repeated for the next sample.
  • a data-driven decisional process is provided to enhance sample throughput by enabling the sample delivery process to act on feedback received from the data acquisition/analysis process.
  • control software 112 makes decisions, such as whether to reject a particular sample during acquisition thereof, or divert a particular sample to a different sample path or analytical instrument, or permit analytical instrument Al to complete the acquisition of that sample, based on feedback from the data acquisition/analysis process.
  • each sample is processed without the time penalties associated with conventional systems, which require the entire sample to be pumped through the system at a nominal flow rate regardless of whether or not data is to be acquired.
  • Block 261 designates the start of the sampling and data acquisition process, and hence is equivalent to block 201 in Figure 10A.
  • Block 263 designates the sample loop flush/instrument flush mode illustrated in Figure 3C and described hereinabove.
  • Block 265 designates the sample loop load/instrument flush mode illustrated in Figure 3B and described hereinabove.
  • Blocks 267 and 269 designate the sample injection/needle rinse mode illustrated in Figure 3A and described hereinabove.
  • the sample (or at least an initial portion of the sample that has been introduced into analytical instrument Al) is analyzed by control software 112 in real time as it is acquired by analytical instrument Al.
  • control software 112 decides whether the sample, the system, and/or instrumentation thereof meets predetermined decision criteria. These criteria can include values based on certain properties of the sample and/or diagnostics or operational/functional states of the system or instrumentation. Non-limiting examples of decision criteria include insufficient sample intensity, thresholding criteria, noise criteria, criteria associated with the presence or absence of a particular peak in a spectrum, and/or criteria associated with the status of analyzing instrument Al.
  • decisions are made by comparing measured, detected, or instrumentation/system-generated values against the predetermined or stored criteria, and determining whether a pass or fail condition exists.
  • all such values used for comparison with the decisional criteria, whether or not such values are derived from the system, its instrumentation, or the sample itself, are characterized as being properties of the sample that are obtained by taking some type of measurement of the sample.
  • control software 112 determines that the sample fails to meet the decision criteria, the current method of data acquisition for that sample is terminated.
  • the remaining sample residing in sample loop SL is discarded at block 275, and the process then returns to block 263, where the sample loop SL, analytical instrument Al, and all associated fluid conduits are flushed in preparation for data acquisition of the next sample.
  • control software 112 can be programmed to cause either a change in the sample injection path or a change in the analytical method to be implemented.
  • An example of changing the sample injection path is to divert the remaining sample (i.e., that portion of the sample that has not yet been processed by or introduced into analytical instrument Al) away from analytical instrument Al to another type of instrument or device for further processing.
  • analytical instrument Al is a mass spectrometer
  • the other instrument or device could be a UV spectrophotometer, a fraction collector, a liquid chromatography device, or another mass spectrometer.
  • An example of selecting or altering a different analytical method is changing one or more settings of analytical instrument Al.
  • control software 112 could cause the mass spectrometer to scan for a different range of mass/charge ratios.
  • control software 112 determines that the sample meets the decision criteria, at block 281 , additional data for that sample can be acquired using the same or new analytical parameters. Data acquisition for that sample is permitted to continue to completion, as indicated by block 283. As shown in Figure 11 , the remaining sample is then discarded at block 285, and the process returns to block 263, where the sample loop SL, analytical instrument Al, and all associated fluid conduits are flushed in preparation for data acquisition of the next sample.
  • Figure 12 illustrates a plot of intensity in counts per second (cps) versus time for a data acquisition process carried out in accordance with the present invention.
  • sampling system 10 illustrated in Figure 1 was equipped with a dual-valve valve assembly VA as described hereinabove with reference to Figures 3A - 3C and an analytical instrument Al in the form of a mass spectrometer.
  • the intensity data was obtained for the 570 - 576 atomic mass unit (amu) range for eight consecutive samples.
  • the samples were processed by the mass spectrometer in 55-second cycle times, with 14 seconds of data acquisition time at maximum intensity for each cycle. No data were acquired during the inter-sample times so that intensity could be plotted as a baseline.
  • the results shown in Figure 12 demonstrate the capabilities of the invention to achieve rapid-fire sample introduction without carryover.
  • Figure 13 illustrates a plot of intensity versus time for a data acquisition process carried out in accordance with the present invention, in comparison to a process carried out by a conventional system.
  • the data acquisition times using the conventional system were approximately 2:39 minutes, while the data acquisition times achieved by the present invention were approximately 1 :59 minutes.
  • Figure 13 thus evidences an approximately 25% improvement in sample throughput by the invention over the conventional system. It will be understood that various details of the invention may be changed without departing from the scope of the invention. Furthermore, the foregoing description is for the purpose of illustration only, and not for the purpose of limitation — the invention being defined by the claims.

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Abstract

Cette invention concerne un procédé, un dispositif et un produit de programme informatique d'acquisition de données à partir d'un échantillon. L'échantillon ou au moins une partie initiale de l'échantillon est transféré dans un instrument d'analyse, lequel recueille des données à partir dudit échantillon. Pendant l'acquisition de données par l'instrument d'analyse, on examine une ou plusieurs propriétés de l'échantillon ou bien l'état du système ou des instruments. On détermine si l'échantillon ou bien le système ou les instruments connexes répondent à des critères basés sur la ou les propriétés mesurées ainsi qu'aux informations d'état. S'il apparaît que l'échantillon, le système ou les instruments ne répondent pas au ou aux critère(s) de décision, l'instrument d'analyse cesse de recueillir des données à partir de l'échantillon en tout ou en partie. S'il s avère en revanche que l'échantillon, le système ou les instruments répondent au ou aux critère(s) de décision, on transfert une partie supplémentaire de l'échantillon dans l'instrument d'analyse pour acquisition de données à partir de cette nouvelle partie d'échantillon. On trouve également un ensemble soupape réglable sur au moins trois mode : mode d'injection de l'échantillon/rinçage de l'aiguille ; mode de charge de la boucle d'échantillonnage/rinçage de l'instrument et mode de rinçage de la boucle d'échantillonnage/rinçage de l'instrument.
PCT/US2002/000064 2001-01-04 2002-01-04 Dispositif, procede et produit de programme informatique pour acquisition automatique de donnees d'echantillonnage a fort rendement WO2002054085A1 (fr)

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US60/259,758 2001-01-04

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5297431A (en) * 1992-06-01 1994-03-29 Thermo Separation Products (California) Inc. Automated sample dilution
US5624846A (en) * 1994-04-28 1997-04-29 Mitsubishi Materials Corporation Continuous flow analyzing method and apparatus
US5633168A (en) * 1995-06-07 1997-05-27 Glasscock; Larry M. Controlled dispersion flow analysis system
US5691486A (en) * 1996-07-30 1997-11-25 Bayer Corporation Apparatus and methods for selecting a variable number of test sample aliquots to mix with respective reagents
US6143573A (en) * 1994-07-11 2000-11-07 Tekmar Company Modular vial autosampler

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5297431A (en) * 1992-06-01 1994-03-29 Thermo Separation Products (California) Inc. Automated sample dilution
US5624846A (en) * 1994-04-28 1997-04-29 Mitsubishi Materials Corporation Continuous flow analyzing method and apparatus
US6143573A (en) * 1994-07-11 2000-11-07 Tekmar Company Modular vial autosampler
US5633168A (en) * 1995-06-07 1997-05-27 Glasscock; Larry M. Controlled dispersion flow analysis system
US5691486A (en) * 1996-07-30 1997-11-25 Bayer Corporation Apparatus and methods for selecting a variable number of test sample aliquots to mix with respective reagents

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