WO2015008281A1

WO2015008281A1 - Sample recording device and system

Info

Publication number: WO2015008281A1
Application number: PCT/IL2014/050637
Authority: WO
Inventors: Israel Schechter; Yehuda Yavets-Chen
Original assignee: Technion Research And Development Foundation Ltd.
Priority date: 2013-07-16
Filing date: 2014-07-15
Publication date: 2015-01-22

Abstract

A sample recording device includes a receptacle with a plurality of reception zones for holding samples dispensed by a dispenser that dispenses samples for later assaying. An association facilitator facilitates association between each of the reception zones and its corresponding sample with a characteristic of the dispensing of that sample.

Description

SAMPLE RECORDING DEVICE AND SYSTEM

FIELD OF THE INVENTION

[0001] The present invention relates to recording of dispensed samples.

BACKGROUND OF THE INVENTION

[0002] In liquid chromatography, a liquid solvent or eluant is used to separate various analytes from a sample mixture. For example, in column chromatography, gravity is utilized to separate the various analytes from one another in a vertical separation column. Each analyte falls through the column at a different rate. The various separated analytes are thus eluted from the solution. The various analytes may be collected as eluates in different containers.

[0003] High-performance liquid chromatography (HPLC) represents an improvement over column chromatography. In HPLC, the solvent is forced through a separation column at high pressure (e.g., 400 atmospheres). In this manner, analytes may be separated from one another much faster than in typical column chromatography. Each of the various analytes passes through the separation column at a rate that is typical for that analyte. The analyte then exits the column as a stream of liquid eluate after the retention time for that analyte. Each eluate may be collected in a container.

[0004] In HPLC, a detector may be utilized to detect various analytes. For example, the detector may include a radiation source and radiation detector. A beam of radiation (e.g., ultraviolet radiation) from the radiation source may be shone through the stream of liquid toward the detector. A reading or signal from the radiation detection is indicative of absorption of the radiation beam by the stream of liquid as a function of time. For example, an analyte may be identifiable by its retention time (e.g., identified via a previous calibration). The reading of the detector may then be indicative of a concentration of the analyte in the eluate.

[0005] Diverting of the analyte to another detector, such as a mass spectrometer, may be utilized to identify the analyte at each retention time. SUMMARY OF THE INVENTION

[0006] There is thus provided, in accordance with some embodiments of the present invention, a sample recording device including a receptacle with a plurality of reception zones for holding samples dispensed by a dispenser dispensing samples for later assaying, and an association facilitator for facilitating association between each of the reception zones and its corresponding sample of the plurality of samples with a characteristic of the dispensing of that sample.

[0007] Furthermore, in accordance with some embodiments of the present invention, the device includes a cover for retaining the samples in the reception zones.

[0008] Furthermore, in accordance with some embodiments of the present invention, the device includes partitions separating adjacent reception zones.

[0009] Furthermore, in accordance with some embodiments of the present invention, the characteristic of the dispensing is selected from the group of characteristics consisting of time of the dispensing of that sample, location of the dispensing of that sample, and source of that sample.

[0010] Furthermore, in accordance with some embodiments of the present invention, the plurality of reception zones is linearly arranged along a strip.

[0011] Furthermore, in accordance with some embodiments of the present invention, the device includes a mechanism for linear translation of the strip to successively bring reception zones of the plurality of reception zones to the dispenser.

[0012] Furthermore, in accordance with some embodiments of the present invention, the plurality of reception zones are distributed in a circular pattern.

[0013] Furthermore, in accordance with some embodiments of the present invention, the plurality of reception zones includes radially oriented grooves.

[0014] Furthermore, in accordance with some embodiments of the present invention, the device includes a mechanism for rotation of the sample recording device so as to successively bring reception zones of the plurality of reception zones to the dispenser.

[0015] Furthermore, in accordance with some embodiments of the present invention, the plurality of reception zones includes capillary tubes. [0016] Furthermore, in accordance with some embodiments of the present invention, the capillary tubes are attached to a foldable strip.

[0017] Furthermore, in accordance with some embodiments of the present invention, each of the capillary tubes includes two electrodes that are electrically isolated from one another.

[0018] Furthermore, in accordance with some embodiments of the present invention, the device includes a mechanism for bringing an end of the capillary tube into contact with the dispensed sample.

[0019] Furthermore, in accordance with some embodiments of the present invention, a reception zone of the plurality of reception zones includes a window that is substantially transparent to electromagnetic radiation in at least one spectral range.

[0020] Furthermore, in accordance with some embodiments of the present invention, each reception zone of the plurality of reception zones includes an electrode.

[0021] There is further provided, in accordance with some embodiments of the present invention, a sample recording cassette including: a housing with an opening; a receptacle enclosed within the housing, the receptacle including a plurality of reception zones for holding samples dispensed by a dispenser dispensing samples for later assaying, and an association facilitator for facilitating association between each of the reception zones and its corresponding sample of the plurality of samples with a characteristic of the dispensing of that sample; and a mechanism for sequentially transporting each reception zone of the plurality of reception zones to the opening so as to allow a sample of the samples that is dispensed by the dispenser to be received by that reception zone.

[0022] Furthermore, in accordance with some embodiments of the present invention, the plurality of reception zones is linearly arranged along a flexible strip.

[0023] Furthermore, in accordance with some embodiments of the present invention, the cassette includes a mechanism for uncoiling the strip or for coiling the strip.

[0024] There is further provided, in accordance with some embodiments of the present invention, a sample recording system including: a receptacle enclosed within the housing, the receptacle including a plurality of reception zones for holding samples dispensed by a dispenser dispensing samples for later assaying, and an association facilitator for facilitating association between each of the reception zones and its corresponding sample of said plurality of samples with a characteristic of the dispensing of that sample; and a motor for driving a mechanism to sequentially transport each reception zone of said plurality of reception zones to the dispenser.

[0025] Furthermore, in accordance with some embodiments of the present invention, the system includes a mechanism for covering each reception zone of the plurality of reception zones after that reception zone has received a sample of the samples.

BRIEF DESCRIPTION OF THE DRAWINGS

[0026] In order to better understand the present invention, and appreciate its practical applications, the following Figures are provided and referenced hereafter. It should be noted that the Figures are given as examples only and in no way limit the scope of the invention. Like components are denoted by like reference numerals.

[0027] Fig. 1A schematically illustrates a system for sample recording, in accordance with an embodiment of the present invention.

[0028] Fig. IB schematically illustrates the sample recording system of Fig. 1A as applied to HPLC eluate recording, in accordance with an embodiment of the present invention.

[0029] Fig. 2A schematically illustrates a sample recording device in the form of a tape, in accordance with an embodiment of the present invention.

[0030] Fig. 2B schematically illustrates a cassette that incorporates the sample recording device shown in Fig. 2A.

[0031] Fig. 3 schematically illustrates a sample recording device in the form of circular disk, in accordance with an embodiment of the present invention.

[0032] Fig. 4 schematically illustrates a sample recording device with reception zones arranged in the form of a square array, in accordance with an embodiment of the present invention. [0033] Fig. 5 A schematically illustrates a sample recording device with reception zones in the form of an array of capillary tubes, in accordance with an embodiment of the present invention.

[0034] Fig. 5B schematically illustrates a capillary tube of the sample recording device shown in Fig. 5A.

[0035] Fig. 6 is a flowchart depicting a method for operation of a sample recording system, in accordance with an embodiment of the present invention.

DETAILED DESCRIPTION OF EMBODIMENTS

[0036] In the following detailed description, numerous specific details are set forth in order to provide a thorough understanding of the invention. However, it will be understood by those of ordinary skill in the art that the invention may be practiced without these specific details. In other instances, well-known methods, procedures, components, modules, units and/or circuits have not been described in detail so as not to obscure the invention.

[0037] In accordance with embodiments of the present invention, a device is provided for recording samples. A sample as used herein may refer to a liquid, gel, or powder that is dispensed by a dispenser. For example, a liquid sample may include a sample of eluate that is produced by application of high-performance liquid chromatography (HPLC). While the description of the present specification describes use of a sample recording device for use with HPLC, it is to be understood that this is just an example, and a sample recording device, according to embodiments of the present invention, may be used in conjunction with other eluate source or sources, or with other types of devices or systems that create or generate eluates or other samples. For example, a sample recording device may be utilized to periodically sample a product that is produced by a production line, or that is being transported by a pipeline.

[0038] A sample recording device according to embodiments of the present invention includes a receptacle with a plurality of reception zones. A reception zone is configured to receive and hold a dispensed sample for later assaying of the sample. For example, a reception zone may include enclosed or partially enclosed spaces, e.g., in the form of a chamber, cavity, indentation, enclosure, groove, of capillary tube, in which a sample may be retained. Such a reception zone may be covered, plugged, or sealed after receiving a sample. As another example, a reception zone may include an absorbent material, such as paper, cardboard, or cloth.

[0039] The reception zones may be physically isolated from one another (e.g., by gaps or partitions), or may include separate spatial regions of a continuous receptacle (e.g., regions of an absorbent strip). The reception zones are arranged in the form of an array of reception zones. The array, in some embodiments, may comprise a single line of reception zones. In some embodiments the array may include a plurality of substantially parallel rows of reception zones, forming a matrix of reception zones. A dispensed sample (e.g., an eluate from HPLC that may contain an analyte) may be placed in each reception zone of the array. Each reception zone is configured to hold or store a sample in a stable and transportable manner. For example, a reception zone may be covered or sealed after receiving a sample.

[0040] The sample recording device is configured with an association facilitator or is otherwise configured to facilitate association of each reception zone with the sample that is held in that reception zone. For example, the association facilitator may include a structure, such as fiducial markings, or a distinguishable end, edge, or corner, that enables unique and unambiguous identification of each reception zone. The association facilitator may include placement of the reception zones at regular spatial intervals so as to enable unique identification of a reception zone by measurement of a distance. The association facilitator may include a unique marking of each reception zone (e.g., printed markings, embossing, perforation, optical marking, magnetic marking, or any other marking that may utilized to identify a reception zone of the sample recording device).

[0041] For example, an eluate that exits a separation column of an HPLC apparatus after a specific retention time may be placed in one of the reception zones of the array. An eluate that exits the separation column after another retention time may be placed in another reception zone of the array. For example, with a sample recording device with a single row of reception zones may be moving at a constant rate relative to a dispenser of the HPLC apparatus (e.g., reception zones that are arranged along a linear strip that is being linearly displaced at a constant speed, or along a perimeter of a circular receptacle that is being rotated at a constant angular velocity). In such a case, each reception zone may be associated with a time that its sample was received. The dispensing time (e.g., retention time) of a sample in a reception zone may be determined by counting reception zones from that reception zone to an indicated starting point, or by measuring a distance from that reception zone to the starting point.

[0042] As used herein, sample recording refers to storage or retention of different samples in reception zones of the sample recording device in a manner that enables identifiable retrieval of the sample that is stored in each reception zone. The storage and retrieval may be automatically controlled.

[0043] As used herein, an array of reception zones refers to any one-, two-, or three- dimensional arrangement of reception zones. For example, the array of reception zones may be arranged linearly along an elongated strip or tape, along the perimeter of a circular disk or other two-dimensional shape, in a matrix or spiral arrangement on a rectangular, cubic, circular, spherical, or other two- or three-dimensional surface, or any other arrangement of multiple reception zones.

[0044] A reception zone as referred to herein may include any structure of which a plurality of such structures may be arranged in the form of an array as defined above. Samples are held by the reception zones in such a manner that a sample that is placed in one reception zone is isolated from a sample placed in any of the other reception zones of the array. For example, a reception zone may include a cavity for holding the sample. As used herein, a cavity may refer to a compartment, groove, indentation, capillary tube, or any other space that may be utilized to hold a sample. A reception zone may include a piece of an absorbent material made out of cloth, paper, cardboard, plastic or other synthetic material, or any other absorbent material, or may include any other type of structure that may be made to hold sample and isolate it from a sample that is held in another reception zone of an array of such structures.

[0045] Each reception zone may be sealable or otherwise constructed so as to retain the held sample for later access. For example, a sealing tape, coating, cap, plug, or membrane may be placed over one or more reception zones of the array after some or all of the reception zones are filled. A sample may be held within a capillary tube by cohesive and adhesive fluid forces, or an open end of the capillary tube may be plugged. [0046] For example, later access may include extraction of some or all of a stored sample, or examination of the sample while contained in the reception zone. An extracted sample may be subjected to analysis to determine its composition. For example, the extracted sample may be subjected to one or more chemical analyses, or to mass spectroscopy, or another analytic technique. The reception zone may be provided with one or more windows that are transparent to electromagnetic radiation on one or more spectral regions, or an extracted sample may be placed in an apparatus that is transparent in that spectral region. The sample may thus be analyzed using one or more optical spectroscopy techniques.

[0047] As used herein, a window is considered to be transparent to radiation in a spectral region when sufficient radiation is transmitted by the window for its intended application. As used herein, a window may refer to a region of a wall, side, surface, or cover of a reception zone (e.g., that is in the form of a cavity), or an entire wall, side, surface, or cover of the reception zone.

[0048] The reception zone may be configured to facilitate multi-photon electron emission spectroscopy (MEES) analysis of the sample. MEES is a method for surface analysis based on multi-photon ionization of atoms or molecules of the surface. MEES analysis includes illuminating the sample with pulses of electromagnetic radiation from a MEES source at a plurality of different wavelengths. The illumination may result in multi-photon ionization of atoms or molecules of the sample. Charged electrodes collect charges (electrons or ions) that are generated by the multi-photon ionization process. A signal that is indicative of the collected charge for each wavelength of illumination is recorded. The resulting spectrum (charge as a function of wavelength) may be analyzed to provide an identification of one or more components of the sample.

[0049] For example, the reception zone may be provided with an electrode, or an extracted sample may be placed on an appropriate MEES electrode. Thus the sample may be exposed to illumination from an appropriate MEES source, while an appropriate electric charge is applied to the electrode, for application of MEES analysis of the sample. When MEES analysis is applied to a sample that is enclosed in a reception zone, a cover of the reception zone may be removed during MEES analysis to enable electron flow between an electrode in the reception zone and an external electrode of the MEES apparatus. Alternatively, a second electrode may be incorporated into the reception zone, or into a cover of the reception zone, to enable MEES analysis of the enclosed sample without opening the reception zone.

[0050] An HPLC system may be configured for operation with sample recording, in accordance with embodiments of the present invention. The HPLC system includes an HPLC apparatus that dispenses eluate during operation, and a sample recording device that includes an array of reception zones. The HPLC system includes a channeling mechanism through which the eluate that is dispensed during each of a plurality of time periods is channeled. For example, the various time periods may correspond to a sequence of successive retention times for the eluate. As another example, the time periods may correspond to separated retention times that are selected in accordance with one or more criteria. The channeling mechanism is configured to channel eluates that are dispensed during different time periods to different reception zones of the sample recording device. The channeling mechanism is controllable in coordination with operation of the HPLC system. The channeling mechanism may be operated to channel eluates with different retention times to different reception zones of the array of reception zones. For example, a controller that operates the channeling mechanism may be in communication with a controller that operates the HPLC system or with a detector that detects analytes that exit a separation column of the HPLC system.

[0051] For example, the channeling mechanism may include a transport mechanism that moves the array of reception zones in coordination with operation of the HPLC system. The transport mechanism may thus be configured to transport a selected reception zone of the array of reception zones to a sampling point in the HPLC system. For example, the sampling point may be positioned opposite an exit opening (e.g., port, nozzle, channel, tube, or pipe) through which an eluate exits from a separation column, detector, or other component of the HPLC system. The transport mechanism may thus bring a different reception zone of the array opposite the exit opening whenever the eluate that is to be sampled is expected to have different analyte content than the previous eluate that was sampled.

[0052] For example, when the array includes reception zones in a linear arrangement, such as along a tape or strip, the transport mechanism may advance the tape or strip to bring a selected reception zone of the array to the sampling point. If the array includes a two- or three-dimensional matrix arrangement, the transport mechanism may translate the array (or translate and rotate the array) to bring a selected reception zone of the array to the sampling point. When the array includes reception zones in a circular or spiral (or spherical) arrangement, the transport may rotate the array (or rotate and translate the array) to bring a selected reception zone of the array to the sampling point.

[0053] A controller of the channeling mechanism or transport mechanism may, in accordance with some embodiments of the present invention, cause reception zones of the array to be filled continuously in sequence. Reception zones of the sample recording device may be filled in a sequential order at fixed time intervals. Thus, the contents of a reception zone may be correlated with retention time by determining the position of that reception zone in the sequence.

[0054] In accordance with some embodiments of the present invention, the controller may be configured to selectively fill reception zones of the array, e.g., in accordance with a condition such as when a predetermined condition is satisfied. For example, the controller may be configured to operate the channeling mechanism such that an HPLC eluate is sampled only when a sensor reading indicates that the eluate includes an analyte, or that a concentration of an analyte in an eluate exceeds a threshold value. The controller may be configured to operate the channeling mechanism such that an eluate is sampled only when a timing mechanism indicates that the current retention time corresponds to an analyte of interest (e.g., in accordance with previously acquired retention time analysis).

[0055] The controller may be configured to record one or more characteristics that are associated with the eluate that is stored in each reception zone of the sample recording device. The characteristics may include, for example, the dispensing time of the sample that is stored in each reception zone, a location where the sample was dispensed (e.g., from a dispenser with multiple dispensing nozzles), a source of a sample, a value that is indicative of a sensor reading corresponding to the sample, or another characterizing value that is related to the sample (e.g., value indicative of analyte concentration in an HPLC eluate). The characteristics may be recorded on the as a marking on sample recording device itself (e.g., encoded in the form of a barcode or alphanumeric code) or on an appropriate medium (e.g., on a removable or non-removable non-volatile computer-readable medium, as a printout, or any other retrievable form) in a manner that is correlated with the reception zone in which the sample is stored. For example, the sample characteristics may be listed in a sequential order in which each characteristic is associated with the corresponding reception zone in a sequence of reception zones on the sample recording device. In the case of a two-dimensional (or three-dimensional) array of reception zones, the characteristic may be correlated with a coordinate of the corresponding reception zone.

[0056] An eluate that is stored using a sample recording device, in accordance with embodiments of the present invention, may be accessed at a later time. For example, an eluate that is stored in a reception zone of the sample recording device may be subjected to assaying or analysis, e.g., at a later date, to determine its contents. The analysis may require sampling or removing contents of a reception zone, or may be performed in situ (e.g., optical analysis via an appropriate transparent wall or window of the reception zone. The reception zone that includes a particular sample may be identified by its sequence in a linear array of reception zones (or in a two- or three-dimensional array in which reception zones are filled in a fixed order), or by its coordinates in a multidimensional array.

[0057] For example, analysis may thus enable identification of HPLC eluate contents of a reception zone independently of the HPLC results. Such identification of the contents may be utilized to correlate HPLC retention time with analyte content of eluates. Determination of the contents may be utilized to resolve ambiguous or disputed HPLC results that are based on retention time alone.

[0058] Fig. 1A schematically illustrates a system for sample recording, in accordance with an embodiment of the present invention.

[0059] Samples are dispensed from sample dispenser 28. For example, dispenser 28 may include one or more nozzles through which a liquid or other sample material is dispensed. A sample is dispensed to one or more reception zones 14 of sample recording device 12. (Reception zones 14 are shown in a linear arrangement. However, the discussion may be understood as referring to any arrangement of reception zones 14.) [0060] Controller 24 controls relative motion between sample dispenser 28 and sample recording device 12. For example, controller 24 may be configured to control operation of drive motor 26. Drive motor 26 may, via transmission 25, control operation of device motion mechanism 27. For example, a device motion mechanism 27 may provide for linear motion of a linear strip (e.g., by linear translation, by rotating a take-up reel about which the strip may be coiled, by rotating a sprocket wheel that engages corresponding perforations in the strip, or by rotating one or more rollers), rotational (or rotational plus translational) motion of a sample recording device 12 with circularly-arranged reception zones 14 (e.g., by rotating a turntable, chuck, or axis), or two- or three-dimensional translational motion of a sample recording device 12 with reception zones 14 arranged in a two- or three-dimensional array (e.g., multi-dimensionally translatable stage).

[0061] Fig. IB schematically illustrates the sample recording system of Fig. 1A as applied to HPLC eluate recording, in accordance with an embodiment of the present invention.

[0062] HPLC sample recording system 10 includes sample recording device 12. Sample recording device 12 cooperates with HPLC apparatus 15.

[0063] Sample recording device 12 includes a plurality of reception zones 14. Each reception zone 14 may be utilized to store an eluate that exits HPLC apparatus 15. For example, each reception zone 14 may include one or more of a piece of absorbent material (including, e.g., paper, cloth, cotton, or a synthetic material), an indentation or cavity, a capillary tube, a walled or partially enclosed region, or any other structure that is capable of holding a sample of a liquid eluate. Although reception zones 14, as shown, are arranged linearly, the reception zones may be arranged in a circular, spiral, matrix, or any other configuration.

[0064] Sample recording device 12 may be transported relative to sample dispenser 28, e.g., by operation of drive motor 26 (operating a transmission and device motion mechanism as shown in Fig. 1A). The motion may include linear motion, (e.g., for use with a linear arrangement of reception zones 14), may include two- or three- dimensional (e.g., for use with a two- or three-dimensional array arrangement of reception zones), may include circular motion (e.g., for use with a circular, spiral, or cylindrical arrangement of reception zones), or any other combination of motions. [0065] In HPLC apparatus 15, a liquid solvent (eluent or mobile phase) is provided from supply container 16. Supply container may include two or more containers, each containing a separate component solvent. The separate component solvents may be mixed together prior to being pumped through separation column 20, or may be pumped separately through separation column 20.

[0066] Pump 18 pumps the liquid solvent through separation column 20. Pump 18 may include two or more separate pumps, each configured to pump a different component of the liquid solvent.

[0067] A sample material to be analyzed by HPLC analysis may be injected into the liquid solvent by sample injector 19. The sample material typically includes various component materials. The sample material may be dissolved in the liquid solvent, forming a mixture of the sample material and liquid solvent.

[0068] Separation column 20 includes a packing material (stationary phase) in the form of particles. Molecules of the sample material may be adsorbed onto the packing material. The relative attraction between molecules of each component of the sample material with the stationary phase and with the mobile phase, as well as other factors (e.g., the applied pressure, particle size of the packing material, and temperature) may determine the retention time for that component material. Thus, various component materials of the sample material are carried by the liquid solvent through separation column 20 at different rates, thus eluting the various component materials from the original mixture. The eluted materials are carried out of separation column 20 as an eluate.

[0069] The eluate may be analyzed by analyzer 22. For example, analyzer 22 may include an optical analyzer that measures absorption of various wavelengths of optical radiation (e.g., ultraviolet radiation) by the eluate. Analyzer 22 may detect when an eluate containing with a relatively large concentration of analyte passes through analyzer 22. Correlation of the time of detention with previously known retention times of various analytes may enable determination of component materials of the sample material. [0070] Eluate may be dispensed by HPLC apparatus 15 via sample dispenser 28. Some or all of the eluate that is dispensed via sample dispenser 28 may be directed to a reception zone 14 of sample recording device 12.

[0071] Sample dispenser 28 may be configured to control flow of eluate from exit HPLC apparatus 15 toward sample recording device 12. For example, sample dispenser 28 may include one or more branches that direct some eluate toward sample recording device 12 and the remainder to a collection receptacle. Sample dispenser 28 may include one or more controllable valves that control flow of eluate into a reception zone 14 of sample recording device 12. Sample dispenser 28 may include one or more sensors or meters for determining a quantity of eluate that flows out of sample dispenser 28, or a rate of flow of eluate through sample dispenser 28.

[0072] Controller 24 may be configured to control relative motion between sample dispenser 28 and sample recording device 12 (e.g., by controlling operation of drive motor 26). Controller 24 may include a single controller device, or two or more intercommunicating controller devices. One or more components of controller 24 may be incorporated into, or may be associated with, HPLC apparatus 15.

[0073] Controller 24 may include one or more processors that are configured to operate in accordance with programmed instructions. For example, controller 24 may include one or more computers or other processing devices.

[0074] Controller 24 may monitor operation of supply container 16 (e.g., monitor selection of component solvents to form the eluent), pump 18 (e.g., monitor a pumping rate), or analyzer 22 (e.g., selection of wavelength of radiation or monitoring analysis results), and motion 26 (e.g., to align a reception zone 14 with sample dispenser 28). Additional function related to HPLC apparatus 15 (e.g., control of flow through sample dispenser 28) or sample recording device 12 (e.g., sealing of reception zones 14) may be controlled or monitored by controller 24.

[0075] Controller 24 may control flow of eluate from sample dispenser 28 to a reception zone 14. For example, controller 24 may operate a valve or barrier to enable flow of the eluate into a reception zone 14 only when a result from analyzer 22 indicates that the eluate includes an analyte (e.g., with a concentration that is greater than a threshold concentration). As another example, controller 24 may limit a volume of flow of eluate into a reception zone 14 in accordance with a known capacity of that reception zone 14. When that reception zone 14 is full, flow of eluate into reception zone 14 may be interrupted. Motion 26 may be applied to bring an empty reception zone 14 in position near sample dispenser 28. Flow of eluate through sample dispenser 28 may be resumed to enable flow of eluate into the empty reception zone 14. Alternatively, or in addition, when a reception zone 14 is full, flow of eluate may be diverted by one or more valves to another collection container, to a waste disposal arrangement, or to another conduit or containment component or facility.

[0076] A sample recording device may be configured to facilitate saving of the eluate in reception zones.

[0077] Fig. 2A schematically illustrates a sample recording device in the form of a tape, in accordance with an embodiment of the present invention.

[0078] Sample recording apparatus 30 includes a sample recording device in the form of sample recording strip 31, configured as an elongated flexible tape. For example, sample recording strip 31 may be initially stored in rolled or coiled form, as represented by supply coil 32. Alternatively, supply coil 32 may represent other suitable configurations for containing and dispensing a length of sample recording strip 31 prior to use. For example, sample recording strip 31 may be initially stored as folded in a suitable container, contained in a sleeve, or in another configuration.

[0079] Reception zones 14 of sample recording strip 31 may be square, rectangular, round, or any other polygonal or rounded shape. Reception zones 14 may include separately formed units that are attached to a tape to form sample recording strip 31. Alternatively, the tape from which sample recording strip 31 is formed may have sufficient thickness to enable formation (e.g., molding or laser forming) of reception zones 14 out of the tape. Alternatively, recording strip 31 may be formed by reception zones 14 that are connected to one another in the form a chained structure.

[0080] Sample recording strip 31 may include a metallic or other electrically conducting material, e.g., at a base of each reception zone 14. The electrically conducting material may be configured (e.g., provided with a suitable connector or lead) for connection to a suitable electrode. For example, connection to an electrode may enable MEES analysis of contents of the reception zone 14. Sample recording strip 31 may be, or may include window regions that are, transparent to radiation in one or more spectral ranges. Such a window may enable optical spectral analysis of the contents of the reception zone 14. A transparent window on one (e.g., upper) surface of reception zone 14 and an optically reflecting and electrically conductive material on an opposite (e.g., lower) surface of reception zone 14, may be utilized to enhance the efficiency of optical spectral analysis of contents of reception zone 14 (e.g., by approximately doubling the optical path of light through a sample held in reception zone 14).

[0081] Operation of device motion mechanism 27 may cause sample recording strip 31 to move in the direction indicated by arrow 33 toward a storage configuration represented by take-up coil 34. Take-up coil 34 may represent a rolled or coiled form, a folded form, or any other suitable mechanism for storing sample recording strip 31 after use and for later access. For example, sample recording strip 31 may be cut between reception zones 14 and stored as separate strips.

[0082] For example, device motion mechanism 27 may include a drive that rotates an axis or a reel around which supply coil 32 or take-up coil 34 (as shown) is wound. Device motion mechanism 27 may include a sprocket wheel that engages corresponding perforations in sample recording strip 31. A mechanism may include one or more rollers for pulling sample recording strip 31 from supply coil 32 toward take-up coil 34. Other mechanisms, any of which may be understood as being represented by device motion mechanism 27, may be used.

[0083] Motion of sample recording strip 31 as represented by arrow 33 may bring reception zone 14a of reception zones 14 opposite sample dispenser 28. When situated opposite sample dispenser 28, a sample may be dispensed by sample dispenser 28 to reception zone 14a. After a predetermined period of time, after a flow of a predetermined quantity of sample into reception zone 14a, or after satisfaction of another suitable condition, motion of sample recording strip 31 moves reception zone 14a past sample dispenser 28. Filled reception zones 14b represent reception zones 14 that have been moved past sample dispenser 28.

[0084] Filled reception zones 14b may be sealed so as to prevent evaporation, spillage, or other loss of a fluid or other sample stored in filled reception zone 14b. For example, a cover tape 36 may be placed over filled reception zones 14b to form covered reception zones 14c. Cover tape 36 may be transparent to one or more ranges of electromagnetic radiation, or may included windows that are transparent to one or more ranges of electromagnetic radiation. Cover tape 36 may be impermeable to an sample that is deposited in covered reception zone 14c. Cover tape 36 may be configured to be perforable (e.g., by a syringe or micropipette) so as to enable extraction of a fluid sample from a covered reception zone 14c (e.g., for chemical analysis or for mass spectrometry analysis). After perforation, cover tape 36 may be re-sealable, e.g., by application of heat.

[0085] Cover tape 36 may be dispensed from a dispenser configuration represented by cover tape coil 38. For example, cover tape coil 38 may represent a rolled or coiled continuous cover tape 36. A mechanism for moving sample recording strip 31 may also operate cover tape coil 38 (e.g., a reel or axis) to dispense cover tape 36 in a manner that is coordinated with motion of sample recording strip 31.

[0086] As another example, individual cover tapes 36, each sized and shaped to cover one, or a few, filled reception zones 14b, may be attached to a continuous backing film or tape. Other dispensing mechanisms or configurations may be utilized.

[0087] As another example, each reception zone may be formed with a cover or as a sealed enclosure. A mechanism for filling the cover (e.g., sample dispenser 28) may be provided with a syringe or other structure for inserting a liquid sample into the reception zone. The reception zone may then be re-sealed, e.g., by application of heat, or by application of a suitable glue or patch.

[0088] A suitable sealing mechanism may be utilized to hold cover tape 36 to covered reception zone 14c. For example, cover tape 36, reception zones 14, or both may include a suitable adhesive for causing cover tape 36 to adhere to edges of a covered reception zone 14c. As another example, thermally applied sealing or welding, electrostatic forces, magnets, mechanical clips or tabs, or any other suitable sealing mechanism may be used.

[0089] After collection of samples, sample recording strip 31 with covered reception zones 14c may be coiled, folded, or otherwise stored, as represented by take-up coil 34. [0090] In accordance with some embodiments of the present invention, all or some components of sample recording apparatus 30 may be incorporated into a self-contained replaceable cassette.

[0091] Fig. 2B schematically illustrates a cassette that incorporates the sample recording device shown in Fig. 2A.

[0092] Although recording device cassette 35 is shown as enclosing sample recording apparatus 30, a recording device cassette may be based on any configuration of reception zones, as described below.

[0093] Recording device cassette 35 encloses all components of sample recording apparatus 30 (Fig. 2A). For example, device motion mechanism 27 may be configured to engage a cooperating drive motor and transmission when inserted into an appropriate frame or holder. The frame or holder may position cassette opening 39 opposite a sample dispenser. When recording device cassette 35 is removed from the holder, cassette opening 39 may be automatically closed.

[0094] A similar frame or holder may position cassette opening 39 opposite a cooperating assaying or analysis device. Such position may enable automated selection and assaying of samples held in one or more reception zones 14.

[0095] In accordance with some embodiments of the present invention, a sample recording device may be in a circular, spiral, or similar configuration. For example, the reception zones of the sample recording device may include radially oriented grooves that are distributed about a central hub or axis.

[0096] Fig. 3 schematically illustrates a sample recording device in the form of circular disk, in accordance with an embodiment of the present invention.

[0097] Circular sample recording device 40 includes a plurality of reception zones in the form of radial groove reception zones 42. In accordance with some embodiments of the present invention, all or some of radial groove reception zones 42 may each be divided into two or more reception zones at different radial distances from an axis of symmetry of circular sample recording device 40. For example, each radial groove reception zone 42 that is so divided may include an appropriate barrier at an appropriate distance from the axis of symmetry. Alternatively, reception zones in a circular recording device may include reception zones arranged in annular sectors of one or more concentric annuli of a circular sample recording device. Other arrangements of reception zones, including, e.g., arc-shaped grooves arranged in concentric circles such a spiral arrangement of reception zones, are possible. Alternatively or in addition to grooves or indentations, the reception zones may include an absorbent material. Reference in the discussion below to a radial groove reception zone 42 may be understood as referring to any reception zone of such alternative configurations.

[0098] Device motion mechanism 27, including an appropriate turntable, axis, or other rotational motion mechanism or arrangement, may be operated to rotate circular sample recording device 40 so as to sequentially bring different radial groove reception zones 42 opposite or near an exit nozzle of an HPLC apparatus (or other apparatus that generates liquid samples) during operation of the HPLC apparatus. In the case where reception zones are arranged at different distances from a rotation axis of circular sample recording device 40, a mechanism may be provided for coordinated rotational and translational motion. For example, device motion mechanism 27 may include a rotational mechanism may be provided for rotating circular sample recording device 40, coordinated with a mechanism for linear motion of the exit nozzle or the rotation axis. The linear motion mechanism may be operated so as to change the distance between the exit nozzle and the rotation axis of circular sample recording device 40. Motion of circular sample recording device 40 may be coordinated with operation of the HPLC apparatus, or various motions of circular sample recording device 40 may be coordinated with one another, via a controller.

[0099] Radial groove reception zones 42 of circular sample recording device 40 may be covered by a disk-shaped cover 44. Alternatively, individual radial groove reception zones 42 or groups of radial groove reception zones 42 may be provided with appropriately shaped reception zone covers, or the reception zones may be initially covered or sealed.

[00100] Radial groove reception zone 42, disk-shaped cover 44 (or an alternatively configured cover), or both, may be transparent or may be provided with a transparent window. When transparent to an appropriate wavelength range of electromagnetic radiation, such transparency may enable spectral analysis of the contents. Similarly, transparency may facilitate exposure of the contents of a radial groove reception zone 42 to radiation from a MEES source for MEES analysis of the contents. Similarly, a radial groove reception zone 42 may include a conducting region to serve as an electrode to enable MEES analysis of contents of radial groove reception zone 42. Radial groove reception zones 42 or disk-shaped cover 44 may be perforable to enable extraction of some or all of the contents of radial groove reception zone 42.

[00101] In accordance with some embodiments of the present invention, all or some components of circular sample recording device 40 may be incorporated into a self-contained replaceable cassette.

[00102] In accordance with some embodiments of the present invention, a sample recording device may have reception zones arranged in a two-dimensional array. For example, the reception zones may be square-shaped and arranged in a two-dimensional regular array.

[00103] Fig. 4 schematically illustrates a sample recording device with reception zones arranged in the form of a square array, in accordance with an embodiment of the present invention.

[00104] Rectangular sample recording device 50 includes a plurality of reception zones, e.g., in the form of square indentation reception zones 52 separated by partitions 53. Rectangular sample recording device 50 may be square or rectangular (or have another polygonal shape). Alternatively or in addition to square indentation reception zones 52, reception zones in a rectangular sample recording device may be rectangularly shaped, may be in the form of parallel elongated strips or grooves, may have polygon-shaped reception zones (e.g., hexagonal reception zones for that may be arranged in a hexagonally close-packed arrangement), may have circular or elliptical reception zones, or may have another arrangement of reception zones. Alternatively to indented reception zones, each reception zone may include an appropriately shaped piece of absorbent material. In the following discussion, any such alternative arrangement of reception zones is to be understood as included when reference is made to square indentation reception zones 52.

[00105] Device motion mechanism 27 may include an appropriate two- dimensional translation mechanism (e.g., translation stage) and may be operated to sequentially bring different square indentation reception zones 52 opposite an exit nozzle of an HPLC apparatus (or other apparatus that generates liquid samples) during operation of the HPLC apparatus. Motion of rectangular sample recording device 50 may be coordinated with operation of a sample dispenser (e.g., of an HPLC apparatus), or various motions of rectangular sample recording device 50 may be coordinated with one another, via a controller.

[00106] Reception zones of rectangular sample recording device 50 may be covered by a rectangular cover 54. Alternatively, individual reception zones or groups of square indentation reception zones 52 (or of alternatively configured reception zones) may be provided with appropriately shaped reception zone covers.

[00107] Square indentation reception zone 52, rectangular cover 54 (or an alternatively configured cover), or both may be transparent to electromagnetic radiation in one or more spectral regions, or may be provided with a window that is transparent in those spectral regions. The window may thus enable spectral analysis of the contents in those spectral regions, or may enable exposure to radiation in those spectral regions (e.g., for application of MEES). Square indentation reception zones 52 may each be provided with a conducting region, such as an electrode 56, which may be utilized in application of MEES analysis. Electrode 56 may be reflecting, and may thus be utilized to facilitate optical spectral analysis of contents of square indentation reception zone 52. Square indentation reception zones 52 or cover may be perforable to enable extraction of some or all of the contents of square indentation reception zones 52.

[00108] In accordance with some embodiments of the present invention, all or some components of rectangular sample recording device 40 may be incorporated into a self-contained replaceable cassette.

[00109] In accordance with some embodiments of the present invention, a sample recording device may include an arrangement of capillary tubes.

[00110] Fig. 5A schematically illustrates a sample recording device with reception zones in the form of an array of capillary tubes, in accordance with an embodiment of the present invention.

[00111] Capillary sample recording device 60 includes an array of capillary tubes 62. For example, capillary tubes 62 may be arranged in a rectangular or close- packed two-dimensional array. Capillary tubes 62 may be arranged in a linear array, e.g., along (and parallel to the width of) an elongated flexible belt, strip, or tape. Such a flexible belt may be coiled, wound, or folded to enable compact storage.

[00112] A capillary tube 62 may be filled by bringing an end 66 of the capillary tube 62 into contact with eluate that exits an exit nozzle of an HPLC apparatus (or other apparatus that generates liquid samples) during operation of the HPLC apparatus. For example, a capillary tube 62a of capillary tubes 62 may be extended outward from capillary sample recording device 60 such that end 66 contacts a stream, drop, or accumulation of eluate.

[00113] The structure of capillary tube 62 may be configured to facilitate analysis of its contents.

[00114] Fig. 5B schematically illustrates a capillary tube of the sample recording device shown in Fig. 5 A.

[00115] For example, a beam of (e.g., monochromatic) electromagnetic radiation may be directed into capillary tube 62 via one end 66. Radiation then passes through the sampled eluate in capillary tube 62 and emerges through the other end 66. A filled capillary tube 62 may serve as a waveguide to channel the radiation through the sampled eluate filling capillary tube 62. Radiation that emerges from the other end 66 may be detected. In this manner, path of the radiation through the sampled eluate is maximized. Spectroscopy is thus facilitated by maximizing attenuation (e.g., absorption or scattering) of attenuated wavelengths and increasing the sensitivity of the spectroscopy measurement. Furthermore, scattered, fluorescent, of evanescent light that exits a transparent wall 68 of capillary tube 62 may be collected, detected, and analyzed.

[00116] Capillary tubes 62 may incorporate one or more electrically conductive electrodes 64a and 64b. Two or more electrodes 64a and 64b are electrically isolated from one another. For example, electrodes 64a and 64b may be produced as metallic inserts (e.g., separated from one another by an electrically insulating strip) that may be inserted into capillary tube 62 prior to filling (or after filling). Separate voltages or charges may be applied to each of electrodes 64a and 64b. For example, one of electrodes 64a and 64b may be positively charged, and the other negatively charged. When appropriate electromagnetic radiation is directed into capillary tube 62 via an end 66, electrodes 64a and 64b may be operated to perform MEES analysis of the sample contained in capillary tube 62.

[00117] Fig. 6 is a flowchart depicting a method for operating a sample recording system, in accordance with an embodiment of the present invention. Reference is made also to components shown in Fig. 1A.

[00118] Sample recording method 100 may be implemented by an appropriate controller, such as controller 24. Controller 24 may control operation of sample recording device 12 in accordance with a sensed status, condition, or configuration of sample dispenser 28 (e.g., of an HPLC apparatus).

[00119] It should be understood with respect to any flowchart referenced herein that the division of the illustrated method into discrete operations represented by blocks of the flowchart has been selected for convenience and clarity only. Alternative division of the illustrated method into discrete operations is possible with equivalent results. Such alternative division of the illustrated method into discrete operations should be understood as representing other embodiments of the illustrated method.

[00120] Similarly, it should be understood that, unless indicated otherwise, the illustrated order of execution of the operations represented by blocks of any flowchart referenced herein has been selected for convenience and clarity only. Operations of the illustrated method may be executed in an alternative order, or concurrently, with equivalent results. Such reordering of operations of the illustrated method should be understood as representing other embodiments of the illustrated method.

[00121] Sample recording method 100 is executed when sample dispenser 28 (or an associated system or apparatus) is operating (block 110). During operation of sample dispenser 28, various samples are dispensed (e.g., after different retention times).

[00122] A reception zone 14 of sample recording device 12 may be placed in position to collect the dispensed sample (block 120). For example, the reception zone 14 may be placed at an appropriate position relative to sample dispenser 28 so as to collect the dispensed sample.

[00123] If no dispensed sample is to be collected (block 130), the reception zone

14 remains in position (return to block 120). For example, in an HPLC system, controller 24 may determine that in accordance with a measured retention time, or in accordance with an analyzer result, insufficient analyte, or no analyte of interest, is present in the eluate that is currently being dispensed by sample dispenser 28. As another example, eluate may be sampled at fixed intervals of retention time.

[00124] If a dispensed sample is to be collected (block 130), sample recording system 10 is operated such that the dispensed sample is collected in reception zone 14 (block 140). For example, controller 24 may determine eluate that is currently exiting through sample dispenser 28 includes an analyte of interest. Sample dispenser 28 may then be operated such that the eluate is directed into the positioned reception zone 14. For example, a valve may be operated or a barrier removed to enable flow of eluate from sample dispenser 28 into the positioned nozzle 14.

[00125] It may be determined that collection of the dispensed sample in the positioned reception zone 14 is complete (block 150). For example, a monitored flow of the dispensed sample may indicate that the reception zone 14 is filled to its capacity or that a predetermined volume of the dispensed sample has exited from sample dispenser 28. A monitored time may indicate that a predetermined time interval has elapsed. As another example, an analyzer of an HPLC system or a previously determined retention time may indicate that the composition of the eluate has changed.

[00126] If collection of the dispensed sample in the reception zone 14 is determined to be complete, the filled reception zone 14 is stored (block 160). For example, the filled reception zone 14 may be moved away from sample dispenser 28, and the filled reception zone 14 may be sealed or covered to prevent loss of the dispensed sample. The filled reception zone 14 may be positioned for storage (e.g., in a coiled roll) for later access.

[00127] One or more values that characterize the dispensed sample that is stored in the reception zone 14 may be recorded in a suitable retrievable manner, e.g., by an appropriate reader. For example, the reader may be associated with an analysis device that may be utilized to assay or analyze contents of a reception zone 14 (e.g., spectral, MEES, chemical, or mass spectroscopy analysis). The reader may be utilized to automatically position one or more reception zones 14 for analysis, or may be utilized to verify the identity of a manually positioned reception zone 14. [00128] Characterizing values may indicate time of dispensing, a location of dispensing, a sample source, or may indicate a position in a sequence of reception zones 14. The characterizing values may be printed (e.g., in encoded form) on reception zone 14 or on a cover of reception zone 14, may be marked in another manner (e.g., a coded sequence of perforations or notches, by attachment of an identifying label, or by other marking), or may be recorded on another medium in a manner that is correlated with the corresponding reception zone 14. As another example, one or more reception zones 14 (e.g., a first reception zone in a sequence, a final reception zone in a sequence, periodically selected reception zones within a sequence) may be marked in a manner that is readable by a suitable reader.

[00129] If more of the dispensed sample is to be collected, an empty reception zone 14 may be placed in position (returning to block 120). With some examples of a sample recording device 12 (e.g., in the form of a strip or tape), positioning the filled reception zone 14 for storage may automatically position an empty reception zone 14 for collecting more of the dispensed sample.

[00130] If collection of the dispensed sample in the reception zone 14 is determined not to be complete (block 150), collection of the dispensed sample in the positioned reception zone 14 continues (returning to block 140).

Claims

1. A sample recording device comprising a receptacle with a plurality of reception zones for holding samples dispensed by a dispenser dispensing samples for later assaying, and an association facilitator for facilitating association between each of the reception zones and its corresponding sample of said plurality of samples with a characteristic of the dispensing of that sample.

2. The device of claim 1 , further comprising a cover for retaining the samples in the reception zones.

3. The device of claim 1 or 2, further comprising partitions separating adjacent reception zones.

4. The device of any of claims 1 to 3, wherein the characteristic of the dispensing is selected from the group of characteristics consisting of time of the dispensing of that sample, location of the dispensing of that sample, and source of that sample.

5. The device of any of claims 1 to 4, wherein said plurality of reception zones is linearly arranged along a strip.

6. The device of claim 5, comprising a mechanism for linear translation of the strip to successively bring reception zones of said plurality of reception zones to the dispenser.

7. The device of any of claims 1 to 6, wherein said plurality of reception zones are distributed in a circular pattern.

8. The device of claim 7, wherein said plurality of reception zones comprises radially oriented grooves.

9. The device of claim 7 or 8, comprising a mechanism for rotation of the sample recording device so as to successively bring reception zones of said plurality of reception zones to the dispenser.

10. The device of any of claims 1 to 9, wherein said plurality of reception zones comprises capillary tubes.

11. The device of claim 10, wherein the capillary tubes are attached to a foldable strip.

12. The device of claim 10 or 11, wherein each of the capillary tubes includes two electrodes that are electrically isolated from one another.

13. The device of any of claims 10 to 12, comprising a mechanism for bringing an end of the capillary tube into contact with the dispensed sample.

14. The device of any of claims 1 to 13, wherein a reception zone of said plurality of reception zones comprises a window that is substantially transparent to electromagnetic radiation in at least one spectral range.

15. The device of any of claims 1 to 14, wherein each reception zone of said plurality of reception zones comprises an electrode.

16. A sample recording cassette comprising:

a housing with an opening;

a receptacle enclosed within the housing, the receptacle including a plurality of reception zones for holding samples dispensed by a dispenser dispensing samples for later assaying, and an association facilitator for facilitating association between each of the reception zones and its corresponding sample of said plurality of samples with a characteristic of the dispensing of that sample; and

a mechanism for sequentially transporting each reception zone of said plurality of reception zones to the opening so as to allow a sample of said samples that is dispensed by the dispenser to be received by that reception zone.

17. The cassette of claim 16, wherein said plurality of reception zones is linearly arranged along a flexible strip.

18. The cassette of claim 17, comprising a mechanism for uncoiling the strip or for coiling the strip.

19. A sample recording system comprising:

a motor for driving a mechanism to sequentially transport each reception zone of said plurality of reception zones to the dispenser.

20. The system of claim 19, comprising a mechanism for covering each reception zone of said plurality of reception zones after that reception zone has received a sample of said samples.