Open port probe interfaces

Abstract

Integrated system for delivering sample to a mass spectrometer, which includes a chamber extending from a top to bottom end, an open port probe disposed in the chamber such that an open end of the probe, which is configured for receiving a sample, is positioned in proximity to top end of the chamber. The system can further include a solvent inlet port coupled to said chamber for receiving a solvent and directing said solvent to said probe, and a solvent outlet port for receiving a flow of the solvent from the open port probe and directing the received solvent out of the chamber. The system can also include an adapter for receiving a sample holder having an outlet port, the adapter is releasable and replaceable and couple with chamber to align the outlet port of sample holder with open end of probe for delivering sample to the probe.

Claims

1. A device for introducing a sample to a mass spectrometer, comprising: a chamber extending from a top end to a bottom end, a sampling probe disposed in said chamber such that a sampling space at an open end of the sampling probe provides a liquid-air interface for receiving one or more sample analytes positioned at or in proximity of said top end of the chamber, said sampling probe having an outlet port configured to be in fluid communication with an ionization source for delivering the one or more sample analytes thereto, a solvent inlet port coupled to said chamber for receiving a solvent and directing said solvent to said sampling space of the sampling probe, a solvent outlet port through which a flow of the solvent is received from the sampling space of the sampling probe and is directed out of the chamber, wherein said chamber is configured for releasable and replaceable coupling at its top end to an adapter that is configured to align an outlet port of a sample holder with said open end of the probe for introduction of a sample to the probe, wherein said top end of the chamber comprises a mounting surface for engaging with a respective mounting surface of said adapter, thereby coupling the adapter to the chamber and wherein said chamber comprises a ridge at said top end thereof, wherein an external surface of said ridge corresponds to said mounting surface of the chamber.

2. The device of claim 1, wherein said ridge is substantially circular.

3. The device of claim 1, further comprising a fixation element for securing said open port probe to said chamber.

4. The device of claim 1, wherein said sample holder comprises any of a pipette, a capillary tube, a melting point tube, a dried blood spot (DBS) card, and a vial cap.

5. The device of claim 1, wherein said adapter comprises a top surface and a sidewall extending downwardly from said top surface, said sidewall including an inner surface configured for engaging with said external surface of said ridge for coupling the adapter to the chamber.

6. The device of claim 5, wherein said adapter comprises a channel having an opening at said top surface, said channel being configured for receiving at least a portion of the open port probe including an open end thereof upon coupling of the adapter to said chamber.

7. The device of claim 6, wherein said adapter comprises an alignment element for receiving at least partially said sample holder so as to align an outlet port of the sample holder with said open end of the open port probe for introduction of a sample contained in the sample holder to the probe.

8. The device of claim 7, wherein said alignment element is configured to receive any of a capillary tube, a melting point tube, a pipette and a dried blood spot card.

9. The device of claim 7, wherein said alignment element comprises a slot formed on the top surface of the adapter.

10. The device of claim 7, wherein said alignment element comprises an inverted, truncated conical surface protruding above said top surface of the adapter and tapering down to said channel opening.

11. A device for introducing a sample to a mass spectrometer, comprising: a chamber extending from a top end to a bottom end, a sampling probe disposed in said chamber such that a sampling space at an open end of the sampling probe provides a liquid-air interface for receiving one or more sample analytes positioned at or in proximity of said top end of the chamber, said sampling probe having an outlet port configured to be in fluid communication with an ionization source for delivering the one or more sample analytes thereto, a solvent inlet port coupled to said chamber for receiving a solvent and directing said solvent to said sampling space of the sampling probe, a solvent outlet port through which a flow of the solvent is received from the sampling space of the sampling probe and is directed out of the chamber, wherein said chamber is configured for releasable and replaceable coupling at its top end to an adapter that is configured to align an outlet port of a sample holder with said open end of the probe for introduction of a sample to the probe, wherein said chamber comprises a bottom cylindrical portion and an upper cylindrical portion, each of said portions having a side wall and wherein said top cylindrical portion has a larger diameter than said lower cylindrical portion.

12. The device of claim 11, wherein an external surface of the sidewall of said top cylindrical portion provides said mounting surface for engaging with the respective mounting surface of said adapter.

13. The device of claim 11, further comprising a partition separating said upper cylindrical portion from said lower cylindrical portion, wherein said partition comprises an opening through which said open port probe extends such that said open end of the probe is positioned in said upper chamber.

14. The device of claim 13, further comprising a disk having an opening and supported by said partition such that the disk opening being in register with the partition opening, said disk having an opening through which the open port probe extends, thereby maintain said open port probe in a desired orientation.

15. An integrated system for delivering a sample to a mass spectrometer, comprising: a chamber extending from a top end to a bottom end, an open port probe disposed in said chamber such that an open end of the probe, which is configured for receiving a sample, is positioned in proximity of said top end of the chamber, a solvent inlet port coupled to said chamber for receiving a solvent and directing said solvent to said open port probe, a solvent outlet port for receiving a flow of the solvent from the open port probe and directing the received solvent out of the chamber, an adapter for receiving a sample holder having an outlet port, wherein said adapter is configured for releasable and replaceable coupling with said chamber so as to align said outlet port of the sample holder with the open end of the probe for delivering the sample to the probe, wherein said chamber comprises a mounting surface at or in proximity of said top end thereof and said adapter comprises a respective mounting surface for releasable and replaceable engagement with the mounting surface of said chamber and wherein said chamber comprises a lower chamber and an upper chamber, and a partition separating the upper and the lower chambers, said partition having an opening so as to allow said open port probe to extend from the upper chamber to the lower chamber such that the open end of the probe is positioned in said upper chamber, wherein said upper chamber comprise a sidewall having an external surface providing said mounting surface of the chamber.

16. A kit for use with a mass spectrometer comprising: a sampling probe that comprises: an open end that is configured to provide a liquid-air interface at a sampling space, an outlet port that is configured to be fluidly connected to an ionization source, a probe aligning apparatus comprising: a chamber extending from a top end to a bottom end, the chamber being configured to receive the sampling probe such that the open end of the sampling probe is positioned at or in proximity of the top end when the sampling probe is disposed in the chamber, an inlet port that is coupled to the chamber that is configured to receive a solvent and is fluidly connected to direct the solvent to the sampling space of the sampling probe, a solvent outlet port that is configured to receive a flow of solvent from the sampling space and is configured to direct solvent from the sampling space to outside of the chamber, two or more different sample holders, two or more adapters configured to interface with the sample holders, the chamber being configured to releasably and replaceably couple at its top end, each of the two or more adapters separately, each of the two or more adapters being configured to align an outlet port of a different sample holder of the two or more different sample holders, with the sampling space of the sampling probe when the sampling probe is disposed in the chamber, wherein said top end of the chamber comprises a mounting surface for engaging with a respective mounting surface of each of the two or more adapters separately, thereby coupling each of the two or more adapters, separately, to the chamber and wherein said chamber comprises a ridge at said top end thereof, wherein an external surface of said ridge corresponds to said mounting surface of the chamber.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) FIG. 1A schematically depicts a sample delivery device in accordance with an embodiment of the present teachings having an open port probe for delivering a sample to a mass spectrometer,

(2) FIG. 1B is a schematic top view of a partition disposed in the delivery device of FIG. 1A to separate a top chamber from a bottom chamber of the device,

(3) FIG. 2 schematically depicts an exemplary implementation of an open port probe suitable for use in the device of FIG. 1A,

(4) FIG. 3A schematically depicts an integrated sample delivery system according to an embodiment of the present teachings, which includes an adapter configured for receiving a sample holder coupled to the sample delivery device depicted in FIG. 1A,

(5) FIG. 3B is a schematic cross-sectional side view of an adapter employed in the system of FIG. 3A,

(6) FIG. 4 schematically depicts an integrated sample delivery system according to another embodiment of the present teachings,

(7) FIG. 5 schematically depicts an integrated sample delivery system according to yet another embodiment of the present teachings,

(8) FIG. 6 is a schematic depiction of a mass spectrometer in which a sample delivery system according to the present teachings is incorporated,

(9) FIG. 7A is an image of a prototype sample delivery device according to the present teachings,

(10) FIG. 7B is an image of a prototype sample delivery system according to the present teachings,

(11) FIG. 8 is an image of another prototype sample delivery system according to the present teachings, and

(12) FIG. 9 is an image of another prototype sample delivery system according to the present teachings having an adapter for coupling to a DBS card.

DETAILED DESCRIPTION

(13) The present teachings are generally directed to devices and systems that allow for efficient delivery of a sample from a sample holder to an open port probe (OPP). In some embodiments, a device containing an OPP is provided that can be releasably and replaceably coupled to a variety of adapters, each configured to facilitate aligning of an outlet port of a sample holder, such as a capillary, melting point tube, a pipette, or a dried blood spot card, to the open end of the OPP. In some embodiments, the adapter can be in the form of a cap that can be releasably and replaceably coupled to the sample delivery device having an OPP. The adapter can include one or more sample alignment elements (features), which can be tailored for a variety of different types of sample introduction to the OPP. Such alignment features can advantageously facilitate the reproducible introduction of a sample to the same location of the open interface of the OPP. The outlet of the OPP can be fluidly coupled to an ion source of a mass spectrometer for delivery of a sample to the ion source. The device and the adapter can collectively form an integrated sample delivery system that can be used for rapid sample introduction for infusion-based mass spectroscopic analysis. For example, the device and the adapter can allow solid surfaces, fluids and flowing capillaries to be guided into position relative to the OPP, thereby allowing improved manual loading of the OPP.

(14) FIG. 1A schematically depicts a device 100 for delivery of a sample to a mass spectrometer. The device 100 includes an open port probe (OPP) 102 that is disposed/inserted in a chamber 104 (herein also referred to as a fluidic chamber, which operates as a probe alignment apparatus), which extends from a top opening 104a to a bottom opening 104b. In this embodiment, the chamber 104 includes an upper portion 106 and a lower portion 108. The upper and the lower portions are substantially cylindrical, though other shapes can also be employed. The upper portion 106 of the chamber 104 includes a sidewall 110 having an inner surface 110a and an outer surface 110b. As discussed in more detail below, the outer surface 110b provides a mounting surface for releasably and replaceably coupling the chamber to an adapter configured to receive a sample holder. In this embodiment, the upper portion 106 is in the form of a circular ridge.

(15) The lower portion 108 of the chamber 104 has a cylindrical sidewall 108a. A tapered transition segment 112 joins the upper portion 106 of the chamber 104 to its lower portion 108. In this embodiment, the upper portion, the tapered transition segment and the lower portion of the chamber 104 are formed as one integral unit, though in other embodiments they can be made separately and joined to one another.

(16) The OPP 102 extends from an open end 102a, which is configured to receive a sample, to an outlet port 102b through which the sample can exit the probe, e.g., to reach a downstream ionization source of a mass spectrometer. The OPP 102 is positioned within the chamber 104 such that a top portion thereof is within the upper portion 106 and the lower portion thereof is within the lower portion 108 of the chamber 104. More specifically, in this embodiment, the OPP 102 passes through an opening 112a (See, FIG. 1B) of a partition 112 disposed between the upper portions 106 and 108 of the chamber 104 to extend between these two portions of the chamber. A disk-shaped element 114, which is supported by the floor of the partition 112, surrounds a portion of the OPP 102 to facilitate maintaining the OPP 102 is a stable orientation within the chamber 104.

(17) In this embodiment, the OPP 102 is positioned substantially vertically within the chamber 104 such its open end 102a is at, or in close proximity of, the top opening 104a of the chamber 104. In other embodiments, the open end 102a of the probe can protrude above the upper portion 106 of the chamber 104.

(18) With continued reference to FIG. 1A, the device 100 further includes a solvent inlet port 116 that includes a connector 116a that protrudes through the sidewall 108a of the lower portion of the chamber outside the chamber for coupling to a source of solvent and a pipe 116b that extends from the connector 116a to the OPP 102. The solvent inlet port can provide a flow of a solvent through the OPP 102. The device 100 further includes a solvent overflow outlet 118 that is coupled to the chamber and protrudes through the sidewall 108a of the lower portion of the chamber through which solvent overflow can be removed from the OPP 102.

(19) The OPP 102 can have a variety of configurations but generally includes an open end, such as the open end 102a, by which a liquid delivered from a sample holder is open to the atmosphere, thus exhibiting a liquid-air interface. The open end can further be configured to receive therethrough a sample containing or suspected of containing one or more analytes. By way of non-limiting example, the sample can comprise a liquid sample that can be introduced (e.g., injected, pipetted, acoustically injected) directly into the liquid present within the sample space. It will likewise be appreciated by those skilled in the art in light of the teachings herein that any liquid (e.g., solvent) suitable for directly receiving a liquid sample, for example, and amenable to the ionization process can be provided in accordance with various aspects of the present teachings.

(20) The device 100 further includes a ground wire 10 for electrically grounding the OPP 102.

(21) FIG. 2 schematically depicts an exemplary implementation of the OPP 102, which can provide a fluid pathway between a sample holder 1 and an ion source 2 such that analytes entrained within a liquid in the sample holder (e.g., desorption solvent) can be delivered to and ionized by the ion source 2. The OPP 102 can have a variety of configurations for receiving a liquid sample through its open end or sampling desorbed analytes from a substrate, but in the depicted exemplary configuration, it includes an outer tube (e.g., outer capillary tube 3) extending from a proximal end 3a to a distal end 3b and an inner tube (e.g., inner capillary tube 4) disposed co-axially within the outer capillary tube 3. As shown, the inner capillary tube 4 also extends from a proximal end 4a to a distal end 4b. The inner capillary tube 4 comprises an axial bore providing a fluid channel therethrough, which as shown in the exemplary embodiment of FIG. 2 defines a sampling conduit 6 through which liquid can be transmitted from the OPP 102 to the ion source 2 via the probe outlet conduit 4c. On the other hand, the annular space between the inner surface of the outer capillary tube 3 and the outer surface of the inner capillary tube 4 can define a solvent conduit 8 extending from an inlet end coupled to the solvent source 5 (e.g., via the probe inlet conduit 49) to an outlet end (adjacent the distal end 4b of the inner capillary tube 4). In some exemplary aspects of the present teachings, the proximal end 4a of the inner capillary tube 4 can be recessed relative to the proximal end 3a of the outer capillary tube 3 (e.g., by a distance h as shown in FIG. 2) so as to define a distal fluid chamber 7 that extends between and is defined by the proximal end 4a of the inner capillary 4 and the proximal end 3a of the outer capillary tube 3. Thus, the distal fluid chamber 7 represents the space adapted to contain fluid between the open proximal end of the probe 102 and the proximal end 4a of the inner capillary tube 4.

(22) Further, as indicated by the arrows of FIG. 2 within the sampling probe 102, the solvent conduit 8 is in fluid communication with the sampling conduit 6 via this distal fluid chamber 7. In this manner, fluid that is delivered to the proximal fluid chamber 7 through the solvent conduit 8 can enter the inlet end of the sampling conduit 6 for subsequent transmission to the ion source 2. It should be appreciated that though the inner capillary tube 4 is described above and shown in FIG. 2 as defining the sampling conduit 6 and the annular space between the inner capillary tube 4 and the outer capillary tube 3 defines the solvent conduit 8, the conduit defined by the inner capillary tube 4 can instead be coupled to the solvent source 5 (so as to define the solvent conduit) and the annular space between the inner and outer capillaries 4, 3 can be coupled to the ion source 2 (so as to define the sampling conduit).

(23) It will be appreciated that sampling probes in accordance with the present teachings can also have a variety of configuration and sizes, with the OPP 102 depicted in FIG. 2 representing an exemplary depiction. By way of non-limiting example, the dimensions of an inner diameter of the inner capillary tube 4 can be in a range from about 1 micron to about 1 mm (e.g., 200 microns), with exemplary dimensions of the outer diameter of the inner capillary tube 4 being in a range from about 100 microns to about 3 or 4 millimeters (e.g., 360 microns). Also by way of example, the dimensions of the inner diameter of the outer capillary tube 3 can be in a range from about 100 microns to about 3 or 4 millimeters (e.g., 450 microns), with the typical dimensions of the outer diameter of the outer capillary tube 3 being in a range from about 150 microns to about 3 or 4 millimeters (e.g., 950 microns). The cross-sectional shapes of the inner capillary tube 4 and/or the outer capillary tube 3 can be circular, elliptical, super-elliptical (i.e., shaped like a super-ellipse), or even polygonal (e.g., square).

(24) As noted above, the device 100 can be releasably and replaceably coupled to a variety of different adapters, which are configured for aligning a sample holder, e.g., the outlet end of a pipette, with the open end of the OPP 102 to allow facile and reproducible delivery of samples to the OPP 102. By way of example, FIG. 3A schematically depicts an integrated sample delivery system 300 according to an embodiment, which includes the device 100 described above, and an adapter 302 that can releasably and replaceably couple to the device 100 to align a sample holder with the open end 102a of the OPP 102. More specifically, with reference to FIG. 3A as well as FIG. 3B, in this embodiment, the adapter 302 includes a top surface 304, and a sidewall wall 306 extending downwardly from the top surface 304. The sidewall 306 includes an inner surface 306a, which can engage with the mounting surface 110b of the upper portion of the fluidic chamber 104 of the device 100 to releasably and replaceably couple the adapter 302 to the sample delivery device 100.

(25) The adapter 302 includes a slot 304a formed in the top surface 304 of the adapter 302 for receiving a sample holder 301, e.g., a pipette in this embodiment. The adapter 302 further includes a central channel 304b that is configured for receiving a top portion of the OPP 102 upon coupling the adapter to the fluidic chamber 104 such that the open end of the OPP 102 is in proximity of, or in contact with, the outlet port of the sample holder positioned in the slot 304a such that the OPP 102 can receive, via its open end, a sample contained in the sample holder.

(26) As noted above, the delivery device 100 having a OPP 102 can be coupled to a variety of different adapters, each configured for aligning one or more types of sample holders to the OPP 102. For example, FIG. 4 schematically depicts another adapter 400 that includes a pipettor alignment fixture 402 that allows a user to rest a pipette tip thereon and guide it to the open end of the OPP 102.

(27) More specifically, similar to the adapter 302 discussed above, the adapter 400 includes a top surface 404 and a sidewall 406 that extends downwardly from the top surface 404, and can be used to engage the adaptor 400 with the top end of the fluidic chamber 104 of the sample delivery device 100. The adapter 400 further includes a channel 408 having a top opening 408a. Upon engagement of the adapter with the fluidic chamber 104, a top portion of the OPP 102 is received in the channel 408 such that the open end 102a of the OPP 102 is substantially flush with the opening 408a.

(28) As noted above, the adapter 400 further includes the alignment fixture 402, which can be used to align a sample holder, e.g., a pipette, with the open end of the OPP 102. In this embodiment, the alignment fixture 402 is in the form of an inverted truncated conical surface that protrudes above the top surface 404 of the adapter 400 with its vertex positioned substantially at the opening 408a. In use, a pipette can be rested on the conical surface 402a of the alignment fixture and its outlet end (tip) can be guided to the open end 102a of the OPP 102 so as to deliver a sample contained in the pipette to the OPP 102.

(29) FIG. 5 schematically depicts an integrated sample delivery system according to another embodiment, which includes the device 100 discussed above and an adapter 500 according to another embodiment, which is configured for coupling to a Dried Blood Spot (DBS) card 502 so as to expose a desired spot to the open end 102a of the OPP 102 of the device 100. More specifically, the adapter 500 includes a sidewall 502 that extends downwardly from a top surface (not visible in this figure) in which a channel is formed, similar to the channels 304b and 408 in the previous embodiments, for receiving a top portion of the OPP 102 such that the open end of the OPP 102 is substantially flush with the top surface of the adapter. In this embodiment, the adapter 500 further includes a DBS card holder 504 for receiving, via an opening 504a thereof, the DBS card 502 and maintaining the card over the top surface of the adapter. More specifically, in this embodiment, the DBS holder 504 is in the form of a bracket having two wings 504b and 504c that facilitate maintaining the DBS card over the OPP 102.

(30) In use, the DBS card 502 is inserted into the DBS holder 504 such that a spot is aligned with the open end of the OPP 102 for extraction of a sample from the spot. After sample extraction from a spot, the adapter can be lifted from the OPP, the card is moved to the next spot and the adapter is placed on the OPP for the next extraction.

(31) The sample delivery device and the adapter can be formed of a variety of suitable materials. For example, in some embodiments, the adapter can be formed of a plastic, such as ABS (acrylonitrile butadiene styrene). In some aspects, the OPP can be formed of stainless steel, plastic, or glass, all by way of non-limiting example.

(32) As noted above, a sample delivery system according to the present teachings can be used to deliver a sample to a mass spectrometer. By way of illustration, FIG. 6 schematically shows a mass spectrometer 600, which includes a sample delivery system 602 according to the present teachings, an ionization source 604 and a mass analyzer 606 disposed downstream of the ionization source. In use, a sample can be introduced to the open end of an OPP of the delivery system 602, which can in turn deliver the sample to the ionization source 604. The ionization source can ionize one or more species in the sample, and the ionized species can be transmitted to the mass analyzer 606 for mass analysis. A variety of ionization sources and mass analyzers can be employed. By way of example, the ionization source can be an electrospray ionization source and the mass analyzer can be any of quadrupole or a time-of-flight mass analyzer.

(33) In some embodiments, various parts of the device described previously may be combined to form a kit, the kit containing two or more interchangable adapters that releasably and replacebly interact and/or engage with the top end of the chamber so as to align an outlet port of a sample holder with the sampling space of the probe. In some embodiments there are at least two different sample holders and each of the at least two adapters is separately configured to align the sampling space of the probe with a different sample holder of the at least two different sample holders.

(34) The following examples are provided by way of providing further elucidation of various aspects of the present teachings, and are not intended to be limiting of the scope of the present teachings.

EXAMPLES

Example 1

(35) FIG. 7A depicts a prototype sample delivery device 700 according to an embodiment, which includes a shell 701 providing a chamber in which an OPP 702 is disposed. The OPP 702 includes an open end 702a providing a liquid-air interface for receiving a sample. FIG. 7B depicts the device 700 coupled to an adapter 703, in the form of a cap, which is releasably coupled to the OPP 702 so as to allow aligning a sample holder, e.g., a capillary tube, to the OPP 702 for delivery of a sample thereto.

Example 2

(36) FIG. 8 shows a prototype sample delivery system 800 according to an embodiment, which includes a sample delivery device 801, such as the above device 700, coupled to an adapter 803. In this embodiment, the adapter 803 includes an alignment element 803a that is configured to guide the tip of a pipette to the open end of the OPP of the sample delivery device 801.

Example 3

(37) FIG. 9 shows another prototype sample delivery system 900, which includes a sample delivery device 901, such as the above device 700, coupled to an adapter 902. In this embodiment, the adapter 902 includes an alignment element 902a, in the form of bracket, for aligning a DBS card with the OPP of the sample delivery device 901.

(38) Those having an ordinary skill in the art will appreciate that various changes can be made to the above embodiments without departing from the scope of the invention. Further, various features of one embodiment can be used with another embodiment.