The present teachings relate to methods and apparatuses that improve the flatness of microplates.
Microplates are used in spotting or filling work stations wherein the microwells receive assays, reagents and/or samples. The microplates may conform to SBS/ANSI (Society for Biomolecular Screening/American National Standards Institute) standard dimensions and may be about 127 millimeters in length by about 85 millimeters in width. The microplate may include a plurality of wells. For example, some microplates can have 6,144 wells or more. The small size and compact spacing of the wells makes the precise alignment of the wells on a spotting or filling work station difficult. While the microplate is typically manufactured to precise dimensions, the level of flatness can deviate from the nominal value to an extent that can lead to dispensed assays, reagents and/or samples missing their targeted wells.
The present teachings provide methods and apparatuses that improve the flatness of the microplates. In some embodiments of the present teachings, a pair of opposing channels that extends along a length of a rigid member is used to retain the microplate on the rigid member and to impart a level of flatness of at least a predetermined value. In some embodiments of the present teachings, one or more rigid framing members each having a channel therein are disposed along the edges of a microplate and impart a level of flatness of at least a predetermined value to the microplate. In some embodiments of the present teachings, a method of flattening the microplate comprises securing the microplate to a rigid member so the microplate has a flatness of at least a predetermined value and maintaining the microplate secured to the rigid member during a subsequent spotting or filling operation. These and other features of the present teachings are set forth herein.
The skilled artisan will understand that the drawings, described below, are for illustration purposes only. The drawings are not intended to limit the scope of the present teachings in any way.
The present teachings provide methods and apparatuses for improving the flatness of high-density microplates. The following definitions and non-limiting guidelines must be considered in reviewing the description of the invention set forth herein.
The section headings used herein are used for organizational purposes only and are not to be construed as limiting the subject matter described in any way. Furthermore, while the present teachings are described in conjunction with various embodiments, it is not intended that the present teachings be limited to such embodiments. On the contrary, the present teachings encompass various alternatives, modifications and equivalents, as will be appreciated by those of skill in the art.
The description and specific examples, while indicating embodiments of the invention, are intended for purposes of illustration only and are not intended to limit the scope of the invention. Moreover, recitation of multiple embodiments having stated features is not intended to exclude other embodiments having additional features, or other embodiments incorporating different combinations of the stated features. Specific examples are provided for illustrative purposes of how to make, use and practice the devices and methods of these teachings and, unless explicitly stated otherwise, are not intended to be a representation that given embodiments of these teachings have, or have not, been made or tested.
As used herein, the word “include” and its variants are intended to be non-limiting, such that recitation of items in a list is not to the exclusion of other like items that may also be useful in the materials, compositions, devices and methods of these teachings.
Referring to
Microplates 26, for which flattening device 22 is configured to retain, have opposite first (upper) and second (bottom) surfaces 28, 30 and a sidewall 32 therebetween, as can be seen in
Microplate 26 can be made from a plastic such as polypropylene with graphite filler. It should be appreciated, however, that other materials such as, but not limited to, glass, silica, plastics, thermal conductive materials, and any other material useful to those skilled in the art can be used for microplate 26. The small size and compact spacing of microwells 34 can make the precise alignment of microwells 34 on a spotting or filling work station 20 difficult. In some embodiments, microplate 26 conforms to SBS/ANSI standard dimensions and is about 127 mm in length by about 85 mm in width. In some embodiments, microplate 26 can have at least 6,144 microwells. While microplate 26 is manufactured to precise dimensions, the level of flatness of microplate 26 can deviate from the nominal value an extent that can lead to dispensed reagents and samples missing their targeted microwells 34.
Flattening device 22 is operable to improve the flatness of microplate 26 to a level that can allow for precise alignment on spotting or filling work station 20 so that the reagents and samples can be accurately placed in the desired well. In some embodiments shown in
Referring now to FIGS. 2 and 3A-B, flattening device 22 can use a rigid microplate or chuck 46 having opposite first and second surfaces 48, 50 and a sidewall 52 therebetween. Chuck 46 can be precisely dimensioned to allow indexing off a portion of sidewall 52 to align on an instrument deck 24 of a work station 20. If desired, chuck 46 can include alignment features that correspond with complementary alignment features on instrument deck 24 to align chuck 46 on instrument deck 24 in a desired position and orientation. In some embodiments, chuck 46 can have a footprint about the size of a microtiter or microplate conforming to SBS/ANSI dimensional standards. In other embodiments, chuck 46 can have a footprint of a differing size. Chuck 46 can be more rigid than microplate 26 to allow chuck 46 to improve the flatness of microplate 26. Chuck 46 can be made from a variety of materials. For example, materials from which chuck 46 can be made include steel, aluminum or other metals or materials including polymers.
Chuck 46 can include a central aperture 54 which extends between first and second surfaces 48, 50. A vacuum fitting 56 can be attached to chuck 46 and can extend from second surface 50. Fitting 56 can communicate with aperture 54 to allow a vacuum source to be connected to chuck 46, as described below.
Two recessed fluid channels 58, 60 can extend longitudinally along first surface 48 of chuck 46. Two other recessed channels 62, 64 can extend laterally along first surface 48 of chuck 46. Fluid channels 58, 60, 62, 64 can all communicate with aperture 54 to allow a vacuum to be pulled between microplate 26 and first surface 48 of chuck 46 to retain microplate 26 in place and improve the flatness, as described below.
As seen in
As seen in
Support member 74 can provide a support surface for the bottom or second surface 30 of microplate 26. Support member 74 can limit deformation of microplate 26 due to the force of the vacuum between chuck 46 and microplate 26. Support member 74 can be a stiff or rigid support or a resilient support that undergoes some deformation due to the force of the vacuum between microplate 26 and chuck 46. As such, support member 74 can be a non-deformable gasket, O-ring or the like, or also function as a sealing member providing a fluid-tight seal between microplate 26 and chuck 46 and made from an elastomer or other resilient material.
Fluid channels 58, 60, 62, 64 can extend beneath support member 74 and can allow a vacuum to be imparted in region 68 of chuck 46 both inside and outside of support member 74. Sealing member 72, support member 74 and first surface 48 of chuck 46 can be dimensioned to provide a planar surface having a flatness equal to or better than a predetermined value when microplate 26 is being held thereon by a vacuum. The vacuum can cause microplate 26 to deform from its nominal dimensions and can result in the predetermined level of flatness, or better, to be imparted to microplate 26. The number of support members 74 and/or sealing members 72 can be increased or decreased to provide a required level of support to the bottom or second surface 30 of microplate 26 to impart a desired level of flatness to microplate 26. Furthermore, the width of sealing member 72 and/or support member 74 can be changed to provide a desired level of support to bottom or second surface 30 of microplate 26. The predetermined level of flatness can be chosen to allow precise positioning of microplate 26 on chuck 46 and subsequently on instrument deck 24 to allow for accurate spotting and/or filling operations by work station 20. By way of non-limiting example, a total flatness equal to or better than 500 microns or a nominal value ±250 microns or less can be the predetermined flatness level imparted by chuck 46 to microplate 26.
Chuck 46 can include alignment features to facilitate the alignment of microplate 26 on chuck 46. In some embodiments, as shown in
Instrument deck 24, as shown in
On instrument decks 24 without opening 82 therein, the chuck can have a different arrangement to account for the lack of the opening in the instrument deck. In some embodiments, as shown in
Referring now to
As shown in
Integrated chuck/deck 192 can use the same alignment features discussed above with reference to FIGS. 2 and 3A-B or, as shown in
In some embodiments according to the present teachings, a flattening device 222 comprises a flattening block 202, as shown in
Flattening block 202 can mechanically retain microplate 226 and can impart a predetermined level of flatness or better to microplate 226. Flattening block 202 can be a rigid member having a rigidity greater than that of microplate 226. Flattening block 202 can be made from a variety of materials including steel, aluminum, or other metals or materials, such as polymers. Flattening block 202 can be precisely dimensioned to allow indexing off a portion of flattening block 202, such as, by way of non-limiting example, the side wall, to align on an instrument deck of a work station. If desired, flattening block 202 can include alignment features that correspond with complementary alignment features on the instrument deck to align flattening block 202 on the instrument deck. In some embodiments, flattening block 202 can have a footprint the size of a microtiter microplate conforming to SBS standards. In some embodiments, flattening block 202 can have a footprint of a differing size. Flattening block 202 can have a top surface 204 that has a flatness of the predetermined level of flatness or better. Top surface 204 can support bottom surface 230 of microplate 226 when positioned on flattening block 202.
Flattening block 202 can comprise opposite top and bottom surfaces 204, 205 with longitudinally extending sidewalls 206, 208 extending therebetween. Bottom surface 205 can be flat and can engage with the instrument deck. Opposing side extensions 206a, 208a of opposing sidewalls 206, 208 of flattening block 202 can extend above top surface 204. Extensions 206a, 208a in conjunction with portions of top surface 204 can form opposing U-shaped channels 210, 212. The openings in channels 210, 212 can face one another. Channels 210, 212 can receive sidewalls 232 of microplate 226 therein. Channels 210, 212 can have an internal vertical height H1 that can be dimensioned to be slightly larger than the nominal thickness H2 of sidewalls 232 of microplate 226 and to impart the predetermined level of flatness or better to microplate 226. In some embodiments, height H1 can equal the nominal thickness H2+500 microns or less. In some embodiments, height H1 can impart a level of flatness of the nominal thickness H2±250 microns.
To attach microplate 226 to flattening block 202, microplate 226 can be slid along top surface 204 with opposing sidewalls 232 disposed in channels 210, 212. The dimensions of channels 210, 212 can be selected to impart the flatness of a predetermined level or better. Channels 210, 212 can have a height H1 that can deform microplate 226, as needed, as microplate 226 is slid along top surface 204 with opposing sidewalls 232 disposed in channels 210, 212. The deformation of microplate 226 by channels 210, 212 can cause microplate 226 to have a level of flatness, at least in the direction parallel to channels 210, 212, to be equal to or better than the predetermined level of flatness. If microplate 226 already has a level of flatness, at least in the direction parallel to sidewalls 232, equal to or better than the predetermined level of flatness, channels 210, 212 may not deform microplate 226 when being inserted into flattening block 202. In some embodiments, the predetermined level of flatness can be 500 microns total or a nominal value ±250 microns.
Flattening block 202 can include alignment features that can facilitate the alignment of microplate 226 thereon. The alignment features can include channels 210, 212, an alignment pin 214 and a plunger mechanism 216. Channels 210, 212 can transversely align microplate 226 on flattening block 202 and can guide microplate 226 as it is slid along top surface 204 of flattening block 202. Pin 214 can engage with slot 236 of microplate 226 to limit the distance along top surface 204 that microplate 226 can be slid and can thereby longitudinally align microplate 226 on flattening block 202. Plunger mechanism 216 can comprise a ball 218 that can nominally extend slightly above top surface 204. A spring 219 can bias ball 218 to its nominal position and can allow ball 218 to be plunged into and retracted below top surface 204 when subjected to a force of an appropriate magnitude. When microplate 226 is slid along top surface 204, bottom surface 230 of microplate 226 can push ball 218 below top surface 204. As slot 236 in microplate 226 comes into full engagement with pin 214, ball 218 can align with aperture 238 in microplate 226. Spring 219 can cause ball 218 to extend upwardly and into engagement with aperture 238. Plunger mechanism 216 can retain microplate 226 in this orientation on top surface 204 of flattening block 202. To remove microplate 226 from flattening block 202, a sliding force of a sufficient magnitude can be imparted upon microplate 226 to overcome the biasing of ball 218 by spring 219. Flattening block 202 can thereby retain microplate 226 thereon and can impart a level of flatness to microplate 226 equal to or better than the predetermined level of flatness through the interaction with channels 210, 212 and top surface 204.
Referring to
During the sliding and deforming phases, transverse alignment of microplate 226 relative to flattening block 202 can be maintained with the interaction of channels 210, 212 with sidewalls 232 of microplate 226, as indicated in block 237. Microplate 226 can be longitudinally aligned relative to flattening block 202, as indicated in block 239, by engaging complementary alignment features on microplate 226 and flattening block 202, such as engaging slot 236 with pin 214. microplate 226 can be retained on flattening block 202 in the aligned position, as indicated in block 241. microplate 226 can be retained on flattening block 202 by engaging ball 218 of plunger mechanism 216 with aperture 238 in microplate 226.
With microplate 226 having the predetermined level of flatness or better and aligned and retained on flattening block 202, a spotting and/or filling operation can be performed, as indicated in block 243. Once the spotting and/or filling operation is completed, microplate 226 can be removed from flattening block 202, as indicated in block 245. Thus, flattening block 202 according to the present teachings can be used to impart a predetermined level of flatness or better to microplate 226 and can facilitate the performing of a spotting and/or filling operation.
In some embodiments, a flattening device 322, as shown in
One or more framing members 321, 323 can be used to impart the predetermined level of flatness to microplate 326. The number of framing members 321, 323 that are used can vary based on a variety of factors. One factor is the degree to which microplate 326 deviates from the predetermined level of flatness and how that deviation occurs. For example, if the deviation is along a longitudinal side of microplate 326, it may be possible to achieve the predetermined level of flatness with the use of a single longitudinal framing member 321. When microplate 326 deviates from the predetermined level of flatness along a lateral side, it may be possible for a single lateral framing member 323 to be used to impart the predetermined level of flatness to microplate 326. In some embodiments, two or more framing members 321, 323 can be used to impart the predetermined level of flatness.
In some embodiments, a longitudinal framing member 321 and a lateral framing member 323 are used to impart the predetermined level of flatness to microplate 326. To facilitate the use of a longitudinal framing member 321 in conjunction with a lateral framing member 323, longitudinal and lateral framing members 321, 323 can be configured to engage with one another in a fixed orientation, such as orthogonal to one another. To accomplish this, lateral framing members 323 can have end portions 329 that can be dimensioned to fit within channels 325 in longitudinal framing members 321. End portions 329 can be dimensioned to provide an interference fit with channels 325. The interference fit can allow lateral framing members 323 to be secured to longitudinal framing members 321 and can thereby facilitate the imparting of a desired level of flatness equal to or better than a predetermined level to a microplate 326.
In some embodiments, end portions 329 can be configured to allow lateral framing members 323 to be secured to longitudinal framing members 321 in a desired position. Alignment features can be used to align a lateral framing member 323 in a specific position relative to a longitudinal framing member 321. For example, as shown in
In some embodiments, longitudinal framing members 321 can include a stop or projection in channel 325 at a desired longitudinal position that can engage with a corner or side of microplate 326 to provide a desired relative orientation between longitudinal framing member 321 and microplate 326.
Framing members 321, 323 can have precise external dimensions that can allow an external surface of framing members 321, 323 to be used to index a position of a microplate 326 disposed therein relative to an instrument deck. To facilitate using an exterior surface of framing members 321, 323 as an indexing feature, a depth D (only shown in
The interaction between sidewalls 332 of microplate 326 and channels 325, 327 can force portions of microplate 326 to conform to the straight and rigid nature of the channels and can thereby impart a level flatness equal to or better than a predetermined value. The framing members 321, 323 can be made from a variety of materials and can be more rigid than microplate 326. For example, suitable materials include steel, aluminum, or other metals or materials, such as polymers.
Referring to
During the insertion process, at least the portions of microplate 326 adjacent the inserted edges are deformed with channels 325, 327, if needed, to impart the predetermined level of flatness or better to microplate 326, as indicated in block 357. The rigid nature of framing members 321, 323 and of the associated channels 325, 327 can cause the side portions of microplate 326 to deform therein.
Also during the insertion process, microplate 326 is aligned within channels 325, 327 of framing members 321, 323, as indicated in block 359. The aligning can include engaging the sidewalls 332 fully within the ends of channels 325, 327 and/or with alignment features within channels 325, 327.
If both a longitudinal framing member 321 and a lateral framing member 323 are being used to impart the predetermined level of flatness to microplate 326, the framing members 321, 323 are connected together in an aligned orientation, as indicated in block 361. The aligned orientation can be achieved by engaging end portions 329 of lateral framing member 323 with the appropriate feature, such as notch 349, in longitudinal framing member 321.
With the longitudinal and lateral framing members 321, 323, as applicable, connected to one another and microplate 326 disposed therein and having been imparted with the predetermined level of flatness, microplate 326 and the framing members 321, 323 can be positioned on the instrument deck and the spotting and/or filling operation performed, as indicated in block 363. After the spotting and/or filling operation is performed, microplate 326 can be removed from framing members 321, 323, as applicable, as indicated in block 365.
Thus, one or more framing members 321, 323, either singularly or in combination, can be used to impart a predetermined level of flatness to a microplate 326. The imparting of the predetermined level of flatness can facilitate a spotting and/or filling operation performed on microplate 326 when disposed on an instrument deck. Framing members 321, 323 can be used to precisely align the flattened microplate 326 on the instrument deck.
While the present teachings are described in conjunction with various embodiments, it is not intended that the present teachings be limited to such embodiments. On the contrary, the present teachings encompass various alternatives, modifications, and equivalents, as will be appreciated by those of skill in the art. For example, the various features and components of the flattening devices disclosed herein can be mixed or interchanged with one another, as desired, to provide the associated benefits and/or advantages of using such features or components. Such variations are not to be regarded as a departure from the spirit and scope of the invention.