Patent Application
20130050692
This invention relates to laboratory analysis devices and more particularly to laboratory analysis devices for holding low-volume solution samples.
Researchers may measure low-volume solution samples using photometric measurement systems and laboratory automation systems. These systems may be adapted to receive cartridges having structures that hold aliquots of a low-volume sample solution during measurement and analysis of the sample solution.
Cross-contamination of sample solutions between experiments may affect researchers' confidence in the accuracy of the measurement and analysis results. Therefore, it may be desirable to clean or decontaminate the cartridges and aliquot-contacting surfaces between uses. It may also be desirable to replace aliquot-contacting surfaces between uses to minimize the risk of cross-contamination.
The aliquot-containing structures in existing designs, however, may be fixed to the cartridge. As a result, adequately cleaning the structures may be timely and costly, and replacing the aliquot-containing structures between uses may be a cost-prohibitive option. Additionally, existing designs may include hinges or other mechanical structures that can wear out or fail thus requiring timely and costly maintenance. Hinges and other mechanical structures may also make existing designs incompatible with automated handlers such as microplate stackers that use grippers.
Therefore, a need exists for an affordable system for measuring and analyzing low-volume solution samples that reduces the risk of cross-contamination and reduces the need for maintenance.
A presentation system for a low-volume solution sample for use in an analysis system is provided. An adapter positions aliquots of the low-volume sample solution for measurement by the analysis system. The adapter includes a recess formed in an upper surface of the adapter for removable receipt of a sample holder that holds the aliquots of the low-volume sample solution. The sample holder is seated in the recess when the sample holder is inserted into the recess. The shape of the recess substantially conforms to at least a portion of the shape of the sample holder such that the recess maintains the sample holder in place during measurement of the aliquots. The recess also has a depth sufficient to receive the sample holder and a cover plate when the sample holder and the cover plate are inserted into the recess.
A method for presenting a low-volume solution sample for use in an analysis system is also provided. A sample holder is inserted into a recess formed in an upper surface of an adapter of a presentation system. The sample holder has aliquots of a low-volume sample solution and is supported in the recess of the adapter. The sample holder is positioned in the recess such that the recess maintains the sample holder in place during measurement of the aliquots by the analysis system. The presentation system is provided to the analysis system for measurement of the aliquots. The presentation system is retrieved when measurement of the aliquots is complete, and the sample holder is removed from the recess of the adapter. A replacement sample holder is inserted into the recess having aliquots of a new low-volume solution sample for a subsequent measurement of the aliquots of the new low-volume sample solution.
Referring to
As seen in
As provided below, the presentation system 100 may be used in the analysis of low volumes of solution samples. The presentation system 100 may be received by an analysis system such as, for example, a microplate reader (not shown), which may illuminate aliquots of a low-volume solution sample with a beam of light to obtain photometric measurements. A low-volume solution sample may be, for example, an aqueous solution around 2-4 microliters (μL) in volume.
The presentation system 100 positions the aliquots of the low-volume solution sample for measurement by the analysis system. For example, the presentation system 100 may position the aliquots of the low-volume solution sample in the light path of a microplate reader. In this example, the dimensions of various components of the presentation system 100 may be kept within a relatively small range of mechanical tolerances to control the placement and positioning of the aliquots for measurement by the analysis system. The particular tolerances may depend, for example, on the volume of the solution sample and the diameter of the light beam. For a low-volume solution sample around 2 μL and a light beam having a diameter around 1 mm, for example, mechanical tolerances of around ±0.1-0.2 mm may be specified.
When positioning the aliquots in the light path for a beam of light, for example, it may be desirable to use a sufficient amount of solution to cover a relatively larger area to ensure that the solution absorbs as much of the beam of light as possible. When measuring aliquots of a low-volume solution sample, however, it may be desirable to measure the individual aliquots over a relatively smaller area. As seen, presentation system 100 controls the placement and positioning of the aliquots of the low-volume solution sample such that, for example, the aliquots cover a minimal amount of surface area while absorbing a maximal amount of light.
Referring to
The adapter 102 includes a recess 112 that may receive a sample holder 104 (
The recess 112 of the adapter 102, in this example, also includes a lip 114 attached to the inner wall 116 that defines the shape of the recess 112. When a sample holder 104 is inserted into the recess 112 of the adapter 102, the sample holder 104 may rest on the lip 114 around the perimeter of the recess 112. Additionally, the adapter 102, in this example, includes one or more (in the illustrated example, two) recesses 118 adjacent to the recess 112 that receives the sample holder 104. The adjacent recesses 118, in this example, may receive the fingers of a researcher or robotic slide handler when placing the sample holder 104 into or removing the sample holder 104 from the adapter 102.
The recess 112 of the adapter 102 may have a predetermined depth sufficient to receive both the sample holder 104 and the cover plate 106 when the sample holder 104 and the cover plate 106 are inserted into the recess 112. The depth of the recess 112 may also be sufficient to support the sample holder 104, for example, at an optimal height in a light path of a beam of light from a microplate reader. As mentioned above, a microplate reader may illuminate the aliquots of the sample holder 104 in order to obtain photometric measurements. The microplate reader may illuminate the aliquots of the low-volume sample solution with a beam of light that narrows as the light approaches the sample holder (i.e., a narrowing cone of light) and expands after the beam of light passes through the aliquots (i.e., an expanding cone of light). In this example, the recess 112 of the adapter 102 may have a depth sufficient to position the sample holder 104 at the narrowest portion of the beam of light.
As an example, the depth of the recess 112 may be sufficient to receive a sample holder 104 around 1 mm thick, a separating member (
In this example, the adapter 102 also includes an opening 117 formed in the lower surface 119 of the adapter 102. The opening 117, in this example, conforms to the size, shape, and position of the recess 112. Accordingly, when the sample holder 104 is seated in the recess 112 of the adapter 102, the adapter 102 does not obstruct a beam of light that illuminates the aliquots of the low-volume solution sample held by the sample holder 104 when obtaining photometric measurements.
The adapter 102 may also include one or more alignment bores 120 for mechanical alignment of the adapter 102 at the analysis system. In this example, the adapter 102 includes four circular alignment bores 120 formed in the upper surface 117 of the adapter 102 and respectively positioned near each of the corners of the adapter 102. The adapter 102 may also include a chamfered corner 122 to ensure proper orientation of the adapter 102 when placing the adapter 102 in or at an analysis system. The chamfered corner 122 of the adapter 102 may physically prevent the adapter 102 from being inserted at the analysis system in an incorrect orientation.
The adapter 102, in this example, has a solid construction and may be made of any dimensionally stable material. For example, the adapter 102 may be constructed from a tempered aluminum alloy such as, for example, 6061-T6 aluminum alloy and may include an anodized finish.
Referring now to
The patterned coating 124 includes multiple apertures 108 that expose respective portions 109 of the upper surface 110 of the substrate 126. The apertures 108 in the patterned coating 124 also function to robustly position aliquots 127 of the low-volume solution sample for measurement by the analysis system. The apertures 108, in this example, spatially constrain the aliquots 127 of the low-volume solution sample to respective exposed portions 109 of the upper surface 110 of the substrate 126. In the example shown in
In some example implementations, the centers of the apertures 108 of the patterned coating 124 may be separated by around 9 mm to correspond to the layout of a standard 96-well microplate. In other example implementations, the centers of the apertures 108 of the patterned coating 124 may be separated by around 4.5 mm to correspond to the layout of a 384-well microplate. In this way, the sample holders 104 are compatible with standard laboratory tools such as multi-channel pipettes and the like.
The size, shape, and positioning of the apertures 108 may determine where the aliquots 127 are positioned for measurement by the analysis system. In the example sample holder 104 shown in
The patterned coating 124 may be made of any material suitable to constrain an aqueous solution for measurement and analysis by an analysis system (e.g., photometric or laboratory automation systems). For example, the patterned coating 124 may be made of materials that are hydrophobic and chemically inert such that the material does not contribute significant contamination to the low-volume solution sample. A fluoropolymer is one example of a material that may be employed for the patterned coating 124 of the sample holder 104.
The patterned coating 124 may be applied to the surface 110 of the substrate 126 of the sample holder 104. The substrate 126 may be made of any dimensionally stable material. The particular material for the substrate 126 may also depend on the type of analysis system in which the sample holder 104 is used. Because the sample holder 104, in this example, is used in photometric measurement systems, light-transmissive materials and materials that do not emit light—such as, for example, glass or plastic—may be selectively employed as the material for the substrate 126 of the sample holder 104. Fluorescence-grade fused silica may be used where a photometric measurement system performs fluorescence measurements since fused silica does not auto-fluoresce and is transparent over a broad range of light wavelengths extending from UV (ultraviolet) through visible to IR (infrared).
The sample holder 104 may also include a chamfered corner 130 to indicate the proper orientation of the sample holder 104 when inserting the sample holder 104 into the recess 112 of the adapter 102. The chamfered corner 130 of the sample holder 104 may likewise physically prevent the sample holder 104 from being inserted into the recess 112 of the adapter 102 in an incorrect orientation.
As discussed further below in reference to
Referring now to
The substrate 135 for the cover plate 106 may also be made of any dimensionally stable material. The material for the substrate 135 of the cover plate 106 may likewise depend on the type of analysis system in which the cover plate 106 is used. Because the sample holders 104, in this example, are used with photometric measurement systems, the substrate 135 may be made of a transparent material such as, for example, quartz glass. In some example embodiments, the cover plate 106 may match the shape (e.g., rectangular) and size (e.g. 76 mm long, 25 mm wide, and 1 mm thick) of the sample holder 104.
The cover plate 106 may include one or more (in the illustrated example, two) separating members 136, i.e., separators, which rest on the upper surface 110 of the substrate 126 of the sample holder 104 and separate the cover plate 106 from the sample holder 104 at a particular distance. In the example shown, the separators 136 of the cover plate 106 are longitudinal separators 136 along the respective longitudinal edges 138 of the cover plate 106. The separators 136, in this example, match the contact regions 132 of the sample holder 104 of
The separators 136 may be attached (e.g., fused) to the lower surface 140 of the cover plate 106 as shown by way of example in
The separators 136 may vary in size. For example, the separators 136 may be 0.5 mm thick, 1 mm thick, etc. The separators 136 of the cover plate 106 may also be color-coded to provide a visual indicator of the thickness of the separators 136 thus making cover plates 106 having separators 136 of different thicknesses easily distinguishable and identifiable. For example, a transparent color may indicate a 0.5 mm separator thickness, and a white color may indicate a 1 mm separator thickness. In some example implementations, the separators 136 of the cover plate 106 may function to establish a path length for absorbance measurements. Like the adapter 102 and sample holder 104, the cover plate 106, in this example, may also include a chamfered corner 142 to ensure proper orientation of the cover plate 106 when the cover plate 106 is placed onto the sample holder 104. Like the chamfered corner 130 of the sample holder 104, the chamfered corner 142 of the cover plate 106 may physically prevent the cover plate 106 from being inserted into the recess 112 of the adapter 102 in an incorrect orientation.
Regarding the absorption path length, a suitable signal-to-noise ratio may be achieved when measuring absorbance of the low-volume solution sample with an absorption path length of, for example, around 0.5 mm. As an example, if the low-volume solution sample is around 2 μL in volume, then an absorption path length of around 0.5 mm may be achieved with apertures 108 (
Referring now to
The sample holder 104 and the cover plate 106 may be placed into the recess 112 of the adapter 102 as shown by way of example in
The presentation system 100 described improves measurement and analysis of low-volume solution samples. Because the adapter 102, in this example, has a solid construction and does not include mechanical structures (e.g., hinged structures) that may wear out, the time and cost associated with maintenance is reduced thereby advantageously increasing the throughput of the analysis systems. Because the adapter 102, in this example, does not include hinged structures or other like mechanical structures, the adapter 102 minimizes the time and cost of servicing the presentation system 100. Furthermore, because the adapter 102, in this example, has a solid construction, it is suitable for use with robotic microplate handlers.
Additionally, because the sample holders 104, in this example, may be constructed of a low-cost material, replacement of the sample holders 104 between uses is an affordable option. The relatively high-cost adapter 102 may be reused while advantageously replacing the relatively low-cost sample holders 104. Moreover, replacing the sample holders 104 between uses advantageously reduces the risk of cross-contamination thereby improving the confidence of the measurement and analysis results. Additionally, the size and shape of the adapter 102 of the presentation system 100, in this example, conforms to the ANSI/SBS standardized microplate dimensions. Accordingly, the presentation system 100 is suitable for use with existing analysis systems, in particular, automated systems having robotic components designed to transport microplates conforming to the standardized dimensions.
In an example method of use, a user may place the adapter 102 of the presentation system 100 in an analysis system and insert the sample holder 104 into the recess 112 of the adapter 102. The user may then apply a low-volume solution sample to a sample holder 104. The patterned coating 124 on the sample holder 104 will spatially constrain aliquots of the low-volume sample solution to the exposed portions 109 of the substrate 126 of the sample holder 104. The recess 112 of the adapter 102 may conform to the size and shape of the sample holder 104 so as to provide a snug fit for the sample holder 104 when the sample holder 104 is seated in the recess 112.
The recess 112 of the adapter 102 may have a depth sufficient to also receive a cover plate 106 to protect the sample holder 104 when the sample holder 104 is seated in the recess 112 of the adapter 102. Accordingly, the user may also insert a cover plate 106 into the recess 112 of the adapter 102 to protect the sample holder 104 during the measurement process. The recesses 118 adjacent to the recess 112 for the sample holder 104 and cover plate 106 permit access of the fingers of the user (or a robotic slide handler) as the user (or robotic slide handler) inserts the sample holder 104 and cover plate 106 into the recess 112 of the adapter 102. In this way, the adjacent recesses 118 provide a convenient pathway for the fingers of the user or a robotic slide handler.
Once the presentation system 100 has been inserted into the analysis system, the analysis system may obtain various measurements (e.g., photometric measurements) of the aliquots of the low-volume solution sample held by the sample holder 104 of the presentation system 100. After the measurement process is complete, the user may retrieve the presentation system 100 from the analysis system. The user may remove the cover plate 106 and sample holder 104 from the adapter 102. The user may clean the sample holder 104 and cover plate 106 to remove the analyzed low-volume solution sample. Cleaning methods such as immersion or sonication may be used where there is risk of cross-contamination; where there is minimal risk of cross-contamination, the user may wipe dry the sample holder 104 before dispensing the next batch of aliquots on the sample holder 104. After the user has cleaned to sample holder 104 and cover plate 106, the user may reassemble the presentation system 100 for a subsequent analysis with a new low-volume solution sample.
The presentation system 100 may be used in a manual fashion as described above or in an automated fashion. The analysis system may include automated material handlers to automatically process multiple presentation systems 100 in a queue (i.e., batch processing). When measurement of the aliquots in one presentation system 100 is complete, the automated handlers may automatically remove the presentation system 100 from the analysis system and automatically replace the presentation system 100 with the next presentation system 100 in the queue. Accordingly, in some example methods of use, the user may prepare multiple presentation systems 100 each having a respective low-volume solution sample from a batch of low-volume solution samples. The user may arrange the multiple presentation systems 100 to form a queue of presentation systems 100. The user may then load the multiple presentation systems 100 into a plate handling robot for automatic analysis of the low-volume solution samples in each respective presentation system 100. The presentation system 100, in this example, is designed to fit into the drawer of, for example, a microplate reader, which allows for this type of sequential batch processing.
The foregoing description of implementations has been presented for purposes of illustration and description. It is not exhaustive and does not limit the claimed inventions to the precise form disclosed. Modifications and variations are possible in light of the above description or may be acquired from practicing the invention. The claims and their equivalents define the scope of the invention.
