Patent Application
20210299671
The disclosed embodiments relate generally to biological specimen collection. In particular, the embodiments relate to a plate for a sampling apparatus and a microcentrifuge vial for a microsampling apparatus.
Traditional clinical diagnostics are performed using blood samples collected by phlebotomy in physician offices or phlebotomy centers. The sample volumes of blood collected by phlebotomy may be up to 10 milliliters.
Alternative sample types are of interest to potentially improve the patient experience and patient convenience. For example, microsampling is a procedure for obtaining and analyzing small biological samples (e.g., 100 microliters or less) for analysis. Microsampling may be performed via fingerstick collection by the patient in a remote location such as their home or office. Fingerstick collection involves pricking the finger of the patient with a needle, allowing a drop of blood to rise to the skin surface, and capturing the drop of blood in an absorbent tip of a testing device. The testing device is then sealed in a case and mailed without refrigeration or special handling to a laboratory for analysis. A full range of analytes may be tested using the small biological sample (e.g., molecular, small molecules, proteins, peptides, etc.). Although fingerstick collection is described in the example above, one of ordinary skill in the art would appreciate that small biological samples (microsamples) may be collected by other known approaches, provided the sample size is 100 microliters or less.
The sample volume required in microsampling may be as much as 500 to 1,000 times less than the sample volume required in traditional clinical diagnostics that are collected, for example, by phlebotomy. The reduced blood volumes collected in microsampling are advantageous, for example, for patients who undergo frequent testing for several analytes where anemia and/or iron deficiency can be a problem. Use of microsampling approaches may be desirable for individuals who fear or dislike phlembotomy, or for individuals with difficult venous access (e.g., young children, obese individuals, etc.). Microsampling also reduces the infrastructure costs associated with traditional diagnostic testing sample collection, which requires a physician office or phlebotomy center.
An example of a microsampling specimen collection device (i.e., a microsampler) is the Mitra® microsampler. Referring to
Before being analyzed, the biological sample must be extracted from the microsampler. In general, a plurality of samples are processed in a single procedure (sequentially or simultaneously). For example, the samples may be processed in a conventional 96 well plate, each configured to receive one sample. As another example, a sample rack may include a plurality of wells that receive test tubes, each configured to receive one sample. Some sample racks may include up to 96 wells or test tubes such that up to 96 samples are processed.
In order to extract the sample, the sampler tip of each microsampler is placed in contact with an extraction buffer that is absorbed in the sampler tip. Next, each sampler tip must be manually removed from the microsampler in order to undergo additional extraction processing (e.g., shaking, heating, or cooling). It takes a long time to manually remove each sampler tip taking care to not contaminate the sample.
In the case of microsampling approaches, the volume of the acquired sample is less than or equal to 100 microliters. When the sampler tip is removed from the microsampler and placed in the bottom of a standard test tube (12 mm×75 mm), there are limitations regarding the type of lab equipment that may be used to recover the sample, obtain liquid from the bottom of the test tube, and analyze the recovered sample.
A need exists for improved technology, including technology that addresses the problems described above.
One exemplary embodiment relates to an apparatus for use in biological sampling. The apparatus includes a plate configured for attachment to a sample rack. The plate includes a plurality of openings extending therethrough, where the plurality of openings each have a non-circular shape that comprises a first portion and a second portion, the first portion having a smaller lateral dimension than the second portion.
According to some embodiments, each of the plurality of openings has a teardrop shape. According to other embodiments, each of the plurality of openings has a keyhole shape. According to still other embodiments, the first portion of the openings is a notched portion.
According to some embodiments, the each of the plurality of openings is configured to receive a sampling device therethrough and the first portion is configured to allow for separation of a sampler tip from the sampling device.
According to some embodiments, the sampling device is a microsampling specimen collection device.
According to some embodiments, the apparatus includes a sample rack, and the plate is coupled to the sample rack.
According to some embodiments, the sample rack is configured to hold a plurality of test tubes that are aligned with the plurality of openings in the plate.
According to some embodiments, a microcentrifuge vial is included that comprises a base and a protrusion extending from the base, where the base is configured for securing the microcentrifuge vial to a test tube. According to some embodiments, an extension extends from the base that defines a channel in which an upper end of a test tube may be received to aid in securing the microcentrifuge vial to the test tube. According to some embodiments, the protrusion is hollow and is configured to receive a biological sample.
According to an exemplary embodiment, a method of extracting a biological sample from a sampling device utilizes an apparatus as recited any of the preceding paragraphs in this section. The method includes inserting at least a portion of a sampling device containing a biological sample through one of the plurality of openings in the plate, the sampling device comprising a sampler body and a sampler tip, wherein the sampler tip is beneath the plate following the insertion. The method also includes moving the sampling device laterally toward the first portion of the opening. The method also includes retracting the sampler body out of the opening to separate the sampler tip from the sampler body.
According to some embodiments, retracting the sampler body out of the opening causes at least a portion of the sampler tip to engage with the plate surrounding the first portion of the opening to cause separation of the sampler tip from the sampler body.
According to some embodiments, the method includes simultaneously performing the steps of the method for a plurality of sampling devices.
According to some embodiments, the method is performed using an automated sample handler.
It should be appreciated that any of the features described in this application may be used in other combinations and with other embodiments than those with which they are primarily described, and all such variations and modifications are intended as being within the scope of the present disclosure.
The disclosure will become more fully understood from the following detailed description, taken in conjunction with the accompanying figures, in which:
Any dimensions identified in the figures are non-limiting examples.
Before turning to the figures, which illustrate the exemplary embodiments in detail, it should be understood that the present application is not limited to the details or methodology set forth in the description or illustrated in the figures. It should also be understood that the terminology is for the purpose of description only and should not be regarded as limiting.
In accordance with an exemplary embodiment, a sampling apparatus or system includes features that are intended to improve the automation of the sample analysis process, as well as allowing for enhanced functionality with respect to microsampling. According to one exemplary embodiment, a sampling rack utilizes a plate that includes a plurality of non-circular holes or openings that facilitate the removal of sampling tips from sampling devices that are used to procure biological samples. The non-circular holes or openings include a portion that has a dimension that is smaller than the sampling device and is configured to allow separation of the sampling tip from the sampling device. The plate may include any number of openings or holes, and in one particular embodiment, may include 96 such openings or holes so as to be compatible with standard sample racks used in the field.
The sampling apparatus or system may also utilize microcentrifuge vials that may be configured to couple to test tubes, vials, or other similar devices. The microcentrifuge vials have a configuration that is intended to allow for the capture or retention of relatively small volume biological samples, and are compatible with centrifuge or other analysis equipment. Once received within the microcentrifuge vial, the sample may be transported to a centrifuge or to other analysis equipment for analysis.
Turning now to
Either or both of the sample rack 10 and the plate 20 can be produced by any suitable process using biocompatible materials that will not affect the analyte analysis. For example, the plate may be produced using additive manufacturing processes (e.g., 3D printing). Other production methods may also be used according to other exemplary embodiments. Alternatively, the plate 20 can be 3D printed (or produced by other processes) and fit to a commercially available sample rack such as that shown as sample rack 10.
As discussed above, the sample rack 10 can have a conventional 96-well configuration (see
Each of the openings 21 is non-circular and has a first portion 21A (shown as a notched or reduced-area portion) and a second portion 21B (shown as a larger portion that has a generally circular shape adapted to allow a test tube or sample vial to be provided therethrough). For ease of reference, the first portion 21A will be referred to hereafter as “notched portion 21A” and the second portion 21B will be referred to as the “larger portion 21B” of the opening 21. The larger portion 21B has a larger lateral dimension as compared to the notched portion 21A.
The larger portions 21B are configured to receive the sampler tip, and the notched portions 21A are configured to assist in separating/removing the sampler tip containing a biological sample therein from the body of a sampling device, as will be described in more detail below.
The plate 20 is configured to attach to the sample rack 10, for example, via snap fit or by inserting fasteners in holes 22 provided in the plate 20. As illustrated in
In operation, the plate 20 is attached to the sample rack 10. One or more sampling devices, each having a sampler tip containing a biological sample, is inserted into the sample rack 10 (one microsampler per well or test tube) from above the plate 20 through the larger portions 21B of the openings 21. The size of the larger portions 21B of the openings 21 is such that larger than that of the sampling device so that the sampling device may easily be inserted through the openings 21 without interference between the sides of the opening and the sides of the sampling device. After insertion, the sampler tip is located beneath the plate 20, while a body and distal end of the sampling device are provided above the plate 20 (see, for example,
Handling of the sampling devices can be automated using a commercially available automated sample handler (e.g., which includes 20-200 microliter pipette heads). According to an exemplary embodiment, the distal end of the sampling device is configured for use with (e.g., will fit) a standard 20-200 microliter pipette head. The automated sample handler may be programmed to pick up the sampling devices via the pipette head and to insert the sampling devices into the sample rack 10 at a desired location. The automated sample handler may also be configured to move the sample devices laterally within the sample rack 10 such that the sampler tips are at least partially located in the notched portions 21A of the openings 21. Once the sampler tips are located in the notched portions 21A, the automated sample handler may move the sampling devices vertically out of the plate 20. As the sampling devices are lifted, the sampler tip cannot fit through the notched portions 21A, which is smaller than the larger portions 21B of the non-circular openings 21. Because the sampler tips cannot pass through the notched portions 21A, the sampler tips will be separated from the sampling device and will remain in the sample rack 10. Thus, using the plate 20 having non-circular openings 21, the sampler tip removal process may be automated. The automated sample holder can be used to move a plurality of sampling devices simultaneously or sequentially.
The plate 20 may be removed prior to performing a process for extracting the sample, or the plate 20 may remain in place while an extraction buffer or water is added to the wells of the sample rack 10.
Referring now to
The microcentrifuge vial 50 is hollow and includes a base 51 (e.g., shown as an annular rim or lip) and a protrusion 52 (e.g., a cup, receptacle, etc.) that extends downward from the base 51. Referring to
The microcentrifuge vial 50 may be manufactured using any suitable process, including via additive manufacturing (e.g., 3D printing). The microcentrifuge vial 50 may be produced in a variety of shapes and sizes configured to be compatible with the type of microsampling device selected or the lab equipment being used.
The microcentrifuge vial 50 may be used in a sampling apparatus including the sample rack 10 and the plate 20 described above. Alternatively, the microcentrifuge vial 50 may be used in a sampling apparatus including the sample rack 10 and plate having circular openings (see, e.g.,
The microcentrifuge vial 50 containing the sampler tip and the extraction buffer or water therein can be removed from the test tube and placed in a centrifuge by itself, or the microcentrifuge vial 50 containing the sampler tip and the extraction buffer or water therein can be placed in a centrifuge while still attached to the test tube. The centrifuge is used to extract the sample from the sampler tip. The biological sample may be, for example, blood, urine, tears, saliva, sweat, serum, cerebral spinal fluid (CSF), plasma, or synovial fluid (although other types of samples can be used in accordance with other exemplary embodiments). The microsampler may be used in conjunction with the microcentrifuge vial 50 and the test tube, but is not necessarily part of the microsampling apparatus.
If desired, instead of using a standard size test tube, the microcentrifuge vial 50 can be fitted to a custom tubular casing 40. In some examples, the tubular casing 40 is a hollow, cylindrical shell that is open on one end thereof in order to receive the microcentrifuge vial 50 (see
Referring to
In a step 120, each of the microcentrifuge vials 50 may be pre-loaded with an extraction buffer or water prior to the sampler tip being inserted into the microcentrifuge vial 50, or an extraction buffer or water may be added to the microcentrifuge vial 50 with the sampler tip already present therein. Removing the sampler tips and then submerging them in the extraction buffer or water prior to performing a sample extraction process increases analyte recovery. The microsampling apparatus may then undergo a sample extraction process in a step 130, which includes one or more known extraction methods such as shaking, heating, or cooling. In some examples, the sample may optionally be dried down under nitrogen and/or reconstituted. The microsampling apparatus is then loaded in a step 140 onto an instrument such as a mass spectrometer or an autoanalyzer (e.g., an Abbott Architect and Beckman-Coulter AU autoanalyzer) to analyze the desired properties of the sample.
Because each of the components of the microsampling apparatus may be 3D printed, material costs are significantly reduced. The microsampling apparatus allows for automated chemistry and sample extraction, and is compatible with various microsamplers and automated sample handler systems.
One versed in the art would appreciate that there may be other embodiments and modifications within the scope and spirit of the disclosure. Accordingly, all modifications attainable by one versed in the art from the present disclosure, within its scope and spirit, are to be included as further embodiments of the present disclosure. Any dimensions included in the accompanying drawings are representative only and are not to be considered defining or limiting in any way, as many variations may be possible.
As utilized herein, the terms “approximately,” “about,” “substantially,” and similar terms are intended to have a broad meaning in harmony with the common and accepted usage by those of ordinary skill in the art to which the subject matter of this disclosure pertains. It should be understood by those of skill in the art who review this disclosure that these terms are intended to allow a description of certain features described and claimed without restricting the scope of these features to the precise numerical ranges provided. Accordingly, these terms should be interpreted as indicating that insubstantial or inconsequential modifications or alterations of the subject matter described and claimed are considered to be within the scope of the disclosure as recited in the appended claims.
It should be noted that the term “exemplary” and variations thereof, as used herein to describe various embodiments, are intended to indicate that such embodiments are possible examples, representations, or illustrations of possible embodiments (and such terms are not intended to connote that such embodiments are necessarily extraordinary or superlative examples).
The term “coupled” and variations thereof, as used herein, means the joining of two members directly or indirectly to one another. Such joining may be stationary (e.g., permanent or fixed) or moveable (e.g., removable or releasable). Such joining may be achieved with the two members coupled directly to each other, with the two members coupled to each other using a separate intervening member and any additional intermediate members coupled with one another, or with the two members coupled to each other using an intervening member that is integrally formed as a single unitary body with one of the two members. If “coupled” or variations thereof are modified by an additional term (e.g., directly coupled), the generic definition of “coupled” provided above is modified by the plain language meaning of the additional term (e.g., “directly coupled” means the joining of two members without any separate intervening member), resulting in a narrower definition than the generic definition of “coupled” provided above. Such coupling may be mechanical, electrical, or fluidic.
The term “or,” as used herein, is used in its inclusive sense (and not in its exclusive sense) so that when used to connect a list of elements, the term “or” means one, some, or all of the elements in the list. Conjunctive language such as the phrase “at least one of X, Y, and Z,” unless specifically stated otherwise, is understood to convey that an element may be either X, Y, Z; X and Y; X and Z; Y and Z; or X, Y, and Z (i.e., any combination of X, Y, and Z). Thus, such conjunctive language is not generally intended to imply that certain embodiments require at least one of X, at least one of Y, and at least one of Z to each be present, unless otherwise indicated.
References herein to the positions of elements (e.g., “top,” “bottom,” “above,” “below”) are merely used to describe the orientation of various elements in the FIGURES. It should be noted that the orientation of various elements may differ according to other exemplary embodiments, and that such variations are intended to be encompassed by the present disclosure.
Although the figures and description may illustrate a specific order of method steps, the order of such steps may differ from what is depicted and described, unless specified differently above. Also, two or more steps may be performed concurrently or with partial concurrence, unless specified differently above. Such variation may depend, for example, on the software and hardware systems chosen and on designer choice. All such variations are within the scope of the disclosure. Likewise, software implementations of the described methods could be accomplished with standard programming techniques with rule-based logic and other logic to accomplish the various connection steps, processing steps, comparison steps, and decision steps.
It is important to note that the construction and arrangement of the components as shown in the various exemplary embodiments is illustrative only. Additionally, any element disclosed in one embodiment may be incorporated or utilized with any other embodiment disclosed herein. For example, the extension shown in the microcentrifuge vial of
The present application claims the benefit of and priority to U.S. Patent App. No. 62/721,590, filed Aug. 22, 2018, the entire disclosure of which, including the specification and drawings, is incorporated herein by reference in its entirety.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/US2019/047564 | 8/21/2019 | WO | 00 |
| Number | Date | Country | |
|---|---|---|---|
| 62721590 | Aug 2018 | US |
