The invention generally relates to a small sample injection vial for interfacing with an analytical instrument.
Capillary electrophoresis (CE) is an analytical method that utilizes differences in electrophoretic mobility between analytes to separate sample substances. Generally, CE is performed in a capillary tube, which is typically open on both ends and to which an electric field is typically applied which causes electrophoretic separation of the analytes within the sample. The electric field is applied by means of electrodes that are arranged at the ends of the capillary and connected to a high voltage power supply. The capillary is filled with an electrically conductive electrolyte so that the electric field can build up within the capillary.
When sample substances are to be introduced into the capillary for subsequent separation, the capillary is generally immersed in a vial containing the sample. In one common method for injecting the sample into the capillary known as electrokinetic injection, electromigration of sample analytes is caused by generating an electric field in the sample through the simultaneous immersion of an electrode that is generally disposed parallel and offset from the electrode. One such exemplary CE instrument utilizing electrokinetic injection is the P/ACE™ MDQ Plus marketed by SCIEX, which can perform an automated CE analysis on a plurality of sample vials contained within a tray. In particular, the tray containing the vials is maneuvered relative to the instrument's capillary/electrode probe such that samples from various vials can be injected and analyzed serially. Though one format of an instrument is to use a single capillary and electrode pair, instruments can be configured with multiple capillary/electrode pairs to analyze sample in parallel (at the same time).
Though CE is well-regarded due its high-resolution separation and minimal volumes of samples and reagents actually utilized in the CE analysis, the sample vials must nonetheless contain a sufficient volume of sample to allow the parallel electrode and capillary to consistently penetrate the liquid. Rather than wide, 2 mL cylindrical vials traditionally utilized in interfacing with some CE instruments, some vendors have recently created narrow vial “inserts” that fit within the standard vials and attempt to “stand up” the fluid in the sample vial by reducing the maximum inner diameter of the vial and by terminating in a frusto-conical bottom (e.g., Eppendorf tubes). Such small-volume inserts typically provide a maximum volume of 200 μL, but nonetheless require a minimum volume of 20-50 μL of sample to insure injection. Accordingly, even in such “small-volume” vials, a significant amount of the sample is wasted as it is unable to be accessed by the sample probe.
In some cases, users only want to use very small sample when the sample is scarce or the sample is very expensive. Using small amounts of sample allows users to perform multiple experiments on the same sample and preserve their valuable sample for future experiments.
Accordingly, there remains a need to eliminate or reduce the waste of expensive and/or scarce samples common in the round vials and vial inserts conventionally used in the art. Because the capillary and the parallel, offset electrode of conventional CE sampling probes must both penetrate the sample, the “narrowing” of conventional vials is necessarily limited by the offset distance between these elements in order to avoid contact with the inner wall of the vial. In accordance with various aspects of the present teachings, Applicants provide a non-round, polarized vial (or insert) that allows for very small sample volumes to be sampled by CE probes, and without giving up large volume containment. Though typically described herein with reference to a capillary electrophoresis (CE) instrument having a parallel electrode and capillary that are to be simultaneously immersed in the sample contained by the sample vial for electrokinetic injection thereof, it should be appreciated that sample vials in accordance with the present teachings are not limited to such use. Rather, a person skilled in the art will appreciate that the present teachings can provide significant reductions in the volume of sample that must be contained within a sample vial for interfacing with a variety of analytical instruments, and particularly, for analytical instruments that interact with a sample via a “polar” or asymmetric probe including in applications such as liquid chromatography and gas chromatography, by way of non-limiting example.
In accordance with various aspects of the present teachings, a vial preferably for use with an asymmetric sampling probe of an analytical instrument is provided, the vial comprising a body extending from a superior end to an inferior end along a longitudinal axis. The body defines a fluid chamber extending from the superior end for containing the sample, wherein a cross-sectional shape of the fluid chamber in at least one plane orthogonal to the longitudinal axis of the body exhibits two or fewer axes of symmetry.
In accordance with various aspects of the present teachings, for example, a vial for use with a capillary electrophoresis (CE) instrument having a sampling capillary and an electrode (the distal ends of which are configured for immersion within a sample contained with the vial), the vial comprising a body extending from a superior end to an inferior end substantially along a longitudinal axis. The body defines a fluid chamber extending from the superior end for containing the sample, wherein a cross-sectional shape of the fluid chamber in at least one plane orthogonal to the longitudinal axis of the body exhibits two or fewer axes of symmetry.
In related aspects, the cross-sectional shapes of the fluid chamber in at least one other plane orthogonal to the longitudinal axis can exhibit more than two axes of symmetry (e.g., circular or square).
In various aspects, the fluid chamber further comprises: a first fluid compartment configured to receive a distal end of an electrode of the CE instrument, and a second fluid compartment configured to receive a distal end of a sampling capillary of the CE instrument, wherein the first fluid compartment and the second fluid compartment are in fluid communication.
In various related aspects, the first fluid compartment extends along a first longitudinal axis and the second fluid compartment extends along a second longitudinal axis, wherein the first and second longitudinal axes are substantially parallel to the longitudinal axis of the body. In some aspects, the first and second longitudinal axes are offset from the longitudinal axis of the body. Additionally, in some aspects, the first longitudinal axis is configured to align with the longitudinal axis of the electrode and the second longitudinal axis is configured to align with the longitudinal axis of the sampling capillary.
In various aspects, the first fluid compartment extends from a superior end to an inferior end, the superior end of the first fluid compartment being inferior to the superior end of the body. Likewise, the second fluid compartment extends from a superior end to an inferior end, the superior end of the second fluid compartment being inferior to the superior end of the body. In related aspects, the inferior end of the first fluid compartment can be inferior to the inferior end of the second fluid compartment.
The first and second compartments can have a variety of shapes. In one aspect, for example, the first and second fluid compartments can be substantially frusto-conical. As noted above, the first and second fluid compartments can be in fluid communication. For example, the first and second fluid compartments can be coupled via a narrow channel. In some aspects, the narrow channel can comprise a narrow gap formed between planar surfaces extending between the first and second fluid compartments. In some related aspects, the superior ends of the first and second substantially frusto-conical fluid compartments are fluidly coupled to an inferior end of a superior fluid compartment. For example, the superior fluid compartment can be a flared compartment from the merger of both the first and second fluid compartments, the superior fluid compartment having a substantially circular cross-sectional shape. In various aspects, the minimum sample volume in the fluid chamber during electrokinetic injection therefrom the fluid chamber can be less than 3 μL (e.g., less than 2 μL).
In various aspects, the cross-sectional shape at an inferior end of the fluid chamber can be substantially rectangular, wherein the major dimension of the cross-section of the fluid chamber is slightly larger than the offset between an electrode and a parallel capillary of a CE probe inserted into the superior end of the fluid chamber and the minor dimension is slightly larger than the diameter of the distal portion of the electrode or capillary. In various aspects, minimum sample volume in the fluid chamber during electrokinetic injection therefrom the fluid chamber can be less than 5 μL.
In accordance with various aspects of the present teachings, an external surface of the body can exhibit a circular cross-sectional shape substantially along its entire length from the superior end to the inferior end. For example, the body can be sized so as to be retained in a conventional sample tray for use with a CE instrument. In some related aspects, the body can exhibit an increased diameter of its external surface adjacent its inferior end so as to retain the body within the sample tray by a compression fit. In various aspects, a tab extends radially from the external surface of the body to aid in proper alignment of the body within the sample tray relative to the electrode and the capillary configuration of the CE instrument. For example, the tab on a first body disposed within the tray prevents a second, adjacent body from being improperly aligned within the tray. Additionally or alternatively, the vial can comprise a second body coupled to the first body, the second body defining a fluid chamber extending from the superior end for containing a second sample, wherein a cross-sectional shape of the fluid chamber in at least one plane orthogonal to the longitudinal axis of the body exhibits two or fewer axes of symmetry, and wherein the fluid chamber of the first and second body are not fluidly coupled. Coupling between the first body and the second body can aid in proper alignment of the bodies within the sample tray relative to the electrode and capillary configuration of the CE instrument.
In some aspects, the body can exhibit an increased diameter of its external surface about an inferior end of the fluid chamber so as to act as a magnifying lens of the sample contained within the fluid chamber.
In various aspects, the maximum volume defined by the fluid chamber can be about 200 μL or greater and the minimum sample volume in the fluid chamber during electrokinetic injection therefrom can be less than about 3 μL and less than about 2 μL.
In accordance with various aspects of the present teachings, a system for use with an asymmetric sampling probe of an analytical instrument is provided, the system comprising a vial comprising a body extending from a superior end to an inferior end along a longitudinal axis, the body defining a fluid chamber extending from the superior end for containing the sample, wherein a cross-sectional shape of the fluid chamber in at least one plane orthogonal to the longitudinal axis of the body exhibits two or fewer axes of symmetry. The system can also include a vial tray configured to retain a plurality of vials.
In various aspects of the system, a tab extends radially from an external surface of the body to aid in proper alignment of the body within the sample tray relative to the electrode and the capillary configuration of the CE instrument. For example, the tab on a first body disposed within the tray can prevent a second, adjacent body from being improperly aligned within the tray.
In some aspects, a second body can be coupled to the first body, the second body defining a fluid chamber extending from the superior end for containing a second sample, wherein the fluid chamber of the first and second body are not fluidly coupled. However, the mechanical coupling between the first body and the second body aid in proper alignment of the bodies within the sample tray relative to the electrode and capillary configuration of the CE instrument.
In some aspects of the present teachings, a sample vial for use with a capillary electrophoresis (CE) instrument is provided, the vial comprising a body extending from a superior end to an inferior end, the body defining a fluid chamber extending from the superior end for containing a sample therewithin, wherein the fluid chamber comprises a first fluid compartment configured to receive a distal end of an electrode of the CE instrument and a second fluid compartment configured to receive a distal end of a sampling capillary of the CE instrument, wherein the first fluid compartment and the second fluid compartment are in fluid communication. For example, the first fluid compartment can extend from a superior end to an inferior end, the superior end of the first fluid compartment being inferior to the superior end of the body, and the second fluid compartment can extend from a superior end to an inferior end, the superior end of the second fluid compartment being inferior to the superior end of the body. Additionally, in some aspects, the fluid chamber can comprise a superior fluid compartment defining a volume extending from the superior end of the body to an inferior end, wherein first and second fluid compartments extend distally from the inferior end of the proximal fluid compartment.
These and other features of the applicant's teachings are set forth herein.
The skilled person in the art will understand that the drawings, described below, are for illustration purposes only. The drawings are not intended to limit the scope of the applicant's teachings in any way.
It will be appreciated that for clarity, the following discussion will explicate various aspects of embodiments of the applicant's teachings, while omitting certain specific details wherever convenient or appropriate to do so. For example, discussion of like or analogous features in alternative embodiments may be somewhat abbreviated. Well-known ideas or concepts may also for brevity not be discussed in any great detail. The skilled person will recognize that some embodiments of the applicant's teachings may not require certain of the specifically described details in every implementation, which are set forth herein only to provide a thorough understanding of the embodiments. Similarly it will be apparent that the described embodiments may be susceptible to alteration or variation according to common general knowledge without departing from the scope of the disclosure. The following detailed description of embodiments is not to be regarded as limiting the scope of the applicant's teachings in any manner. As used herein, the terms “about” and “substantially equal” refer to variations in a numerical quantity that can occur, for example, through measuring or handling procedures in the real world; through inadvertent error in these procedures; through differences in the manufacture, source, or purity of compositions or reagents; and the like. Typically, the terms “about” and “substantially equal” as used herein means greater or lesser than the value or range of values stated by 1/10 of the stated values, e.g., ±10%. For instance, a concentration value of about 30% or substantially equal to 30% can mean a concentration between 27% and 33%. The terms also refer to variations that would be recognized by one skilled in the art as being equivalent so long as such variations do not encompass known values practiced by the prior art.
In accordance with various aspects of the applicant's teachings, the methods and systems described herein can reduce the minimum volume of sample fluid required to be contained with a sample vial when interfacing the sample vial with an analytical instrument, and particularly, for use in analytical instruments that interact with a sample via a “polar” or asymmetric probe, including in capillary electrophoresis, liquid chromatography, and gas chromatography, by way of non-limiting example. In various aspects, the vials can reduce the waste of expensive and/or scarce samples common in the round vials and vial inserts conventionally used in the art, without sacrificing the ability to use the vials with high-volume analyses. Importantly, in some aspects, the outer shape of the vials according to the present teachings can be substantially identical to the conventional vials that currently used on CE instruments, though the inner shape (i.e., the shape of the fluid chamber) can be formed to optimize low-volume applications. Unlike most conventional vials that allow for a useable range of about 10× (200 μL to 2 mL full scale for large volume or 20 μL to 200 μL full scale for small volume inserts), the present teachings can allow for accommodating volumes less than about 2 μL to about 200 μL full scale, by way of non-limiting example. Thus, vials in accordance with various aspects of the present teachings can provide drastically-reduced minimum volume from which electrokinetic injection can occur, as well as a ˜10× improvement in sample-size range over current designs currently used.
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In light of the lack of full symmetry provided in vials in accordance with various aspects of the present teachings,
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Because of the particularly small sample volumes enabled by the present teachings, the exemplary vial 400 additionally includes an increased diameter portion 430 about the inferior end of the fluid chamber 416. When the vial 400 is formed from a transparent material, this convex, bulge portion 430 can function as a magnifying window so as to view the sample within the fluid chamber 416. Additionally, as shown in
The section headings used herein are for organizational purposes only and are not to be construed as limiting. While the applicant's teachings are described in conjunction with various embodiments, it is not intended that the applicant's teachings be limited to such embodiments. On the contrary, the applicant's teachings encompass various alternatives, modifications, and equivalents, as will be appreciated by those of skill in the art.
This application claims the benefit of priority from U.S. Provisional Application Ser. No. 62/221,094, filed on Sep. 20, 2015, the entire contents of which is incorporated by reference, herein.
Filing Document | Filing Date | Country | Kind |
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PCT/IB2016/055608 | 9/20/2016 | WO | 00 |
Number | Date | Country | |
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62221094 | Sep 2015 | US |