Patent Application
20240382967
Modern life science research encompasses disciplines such as genetics, genomics, proteomics, and synthetic sequencing. In each of these disciplines, the modification, processing, and/or analysis of liquid biological and chemical samples of interest is fundamental. Thus, thermocyclers are integral to life science research. For example, in molecular biology research alone thermocyclers are used, among other things, for DNA sequencing, cloning, generation of probes, quantification of DNA and RNA, studying patterns of gene expression, and detection of sequence-tagged sites.
Thermocyclers are devices capable of precise temperature control. In some instances, a thermocycler can be configured to regulate temperatures in complicated cyclical programs. A thermocycler typically fully encloses a labware containing liquid samples under a lid mechanism to ensure tightly controlled thermal conditions. A thermal block-typically a piece of fabricated metal such as aluminum-thermally couples the labware (and thereby the liquid samples) to a thermal control system of the thermocycler. Because of this ability to hold precise temperatures with little fluctuation, thermocyclers are commonly used for amplification of DNA and RNA samples, such as by Polymerase Chain Reaction (PCR). In PCR, a thermocycler applies rapid thermal changes to liquid biological and chemical samples. Accordingly, thermocyclers are well suited for any laboratory process where strict temperature control is required.
Various laboratory processes require an airtight seal to be created between the lid mechanism of the thermocycler and each individual liquid sample in the labware. In some cases, this is to prevent evaporation of the liquid samples during protocols involving high temperatures. In some other cases, an air tight seal is required to prevent contamination. Therefore, a sealing sheet, often formed of a sheet of compressible material (e.g., a polymer or silicone), is applied to the lid mechanism of the thermocycler so that an airtight seal is created between the lid mechanism and the labware when the lid mechanism is closed.
However, in some instances, the sealing force applied to actuate the airtight seal between the thermocycler lid and the labware create a challenge downstream when trying to remove the labware from the thermal block. That is, the labware often remains adhered to the thermal block at the end of a laboratory process, requiring the labware to be forcefully lifted from the thermal block. This forceful lifting can upset the contents of the labware and lead to spillage, contamination, sample loss, and more. In general, the temperature cycling that occurs during thermocycler processes often causes repeated thermal expansion and contraction of the labware and/or thermal block. As such, the thermal cycling coupled with a strong compression force from the airtight seal can increase the likelihood that the labware ends up needing to be forcefully removed from the thermal block.
The Detailed Description is set forth with reference to the accompanying figures. In the figures, the left-most digit(s) of a reference number identifies the figure in which the reference number first appears. The use of the same reference numbers in different figures indicates similar or identical items. Furthermore, the drawings may be considered as providing an approximate depiction of the relative sizes of the individual components within individual figures. However, the drawings are not to scale, and the relative sizes of the individual components, both within individual figures and between the different figures, may vary from what is depicted. In particular, some of the figures may depict components as a certain size or shape, while other figures may depict the same components on a larger scale or differently shaped for the sake of clarity.
The thermocycler device 100 includes a lid 104, which is shown disposed in an open position. The labware 102 is shown disposed within a thermal block 106 of the thermocycler device 100. The thermal block 106 thermally couples the labware 102 to the thermocycler device 100 such that the thermal transfer may be controlled by the thermal control system.
As shown in in
Conventional thermocycler devices, like thermocycler device 100, typically include a lid securing mechanism for closing and securing the lid 104 during operation. An example lid securing mechanism 110a/110b may include a latch (110a) and catch (110b) system, such as the push-to-close latch system shown in
In an embodiment of the instant disclosure, the thermocycler device may use the opening movement of the lid of the thermocycler device to actuate a mechanical and/or electrical system/apparatus within the thermocycler device. This actuation may cause a separation of a labware from the thermal block (i.e., a controlled release) after use. For example, the angular motion of the lid as it pivots from closed to open may be converted to cause a linear motion of a component of the mechanical and/or electrical system/apparatus. The linear motion of the component is used to cause rotational movement of one or more gears which are configured to cause a lifting action on a base of the labware, thereby effectuating the desired separation. Other mechanical actuation methods are contemplated and discussed in part below.
Turning the embodiment depicted in
In general, the apparatus 202 may function to separate the labware from the thermal block 204 by shifting the position of the gear rack 210, which causes the gear 212 to rotate (along a fixed axis with respect to the body 208) via engagement with the set of teeth 214. The rotation of the gear 212 ultimately provides a lifting force, as described in more detail below, between the labware and the thermal block 204. Note, as depicted, the gear 212 is fixedly pivotable with respect to the body 208, however, in an alternative embodiment not shown, a gear may be translatable and fixedly pivotable with respect to the gear rack 210, and a set of teeth may be fixedly positioned with respect to the body 208. Moreover, in an embodiment, one or more apparatuses 202 may be incorporated into the thermocycler device, such as the two shown on opposite lateral sides of the thermocycler device 200. For the sake of clarity, the references only explicitly point out the features on one side.
With further respect to the function of the apparatus 202, the gear 212 may engage a rotary cam (a component not shown in
Though many alternative means of actuating the gear rack 210 are conceivable, as stated above, the embodiment depicted in
The translational movement of the gear rack 210 may be effectuated, at least in part, due to the shapes and structural arrangement of the gear rack 210 and the connection member 216. For example, the adjacent ends of the connection member 216 and the gear rack 210 may be correspondingly shaped such that motion of the lid 206, such as the angular motion that occurs when opening or closing the lid 206 via pivoting the connection member 216, forces the gear rack 210 to change position through a sliding translational movement. The translational sliding of the gear rack 210 causes the lifting force between the labware and the thermal block 204. This dual activity is also due, at least in part, to the vertical orientation and elongation of the aperture (see
Note, as indicated above with respect to the potential for an embodiment to have one or more than one apparatus 202, it is to be understood that the additional components, discussed in greater detail hereinafter, may also be incorporated and/or claimed as one or as multiples of the components (i.e., one or more gears, a plurality of sets of teeth, at least one guide, etc.). Nevertheless, the components may be discussed in terms of singularity for convenience and for simplicity, unless, for example, a specific description of a plurality is helpful to explain a particular aspect of the disclosure.
In an embodiment, the gear rack 210 may have a shape profile of an elongated flattened bar, where the thickness dimension of the bar is less than a width of the bar, and the width dimension of the bar is less than a length dimension of the bar. The gear rack 210 may be positioned such that the length dimension thereof extends in a front to back direction of the thermocycler device 200, and the width dimension extends in a top to bottom direction of the thermocycler device 200.
The gear rack 210 may include an aperture 302 (e.g., slot, cavity, pathway, channel, hole, etc.) that passes through the gear rack 210 in the thickness direction and that extends elongatedly in the direction of the length of the gear rack 210. The aperture 302 may be located proximate to the set of teeth 214, though not necessarily in alignment either in length or vertical disposition along the length of the gear rack 210. In an embodiment, the aperture 302 may have a non-linear profile inside wall shape. That is, in an embodiment as depicted, the inner wall surface of the aperture 302 may have a wider opening dimension closer to the outer edge, which is the side of the gear rack 210 facing away from the thermal block 204. Alternatively, in an embodiment not shown, the aperture 302 may have a straight profile (i.e., linear and non-slanted with respect to the outer face of the gear rack 210) inner wall surface, or a varied wall surface having more than one dimensional change in the wall shape (or depth into the thickness of the gear rack 210).
Inasmuch as the gear rack 210 may be translatable in a front to back direction (when embodied as depicted on the lateral side of the thermocycler device 200), the set of teeth 214 may be disposed on an upper side (in the width direction) of the gear rack 210. The set of teeth 214 may thus protrude away from the upper side of the gear rack 210 in the width direction and may be disposed consecutively in a linear extension along the length direction on the upper side of the gear rack 210. Positioned as such, the set of teeth 214 are configured to be aligned to engage with the gear 212. As such, the gear 212 may be a circular gear having teeth around the perimeter with a pitch that corresponds to roll within the pitch of the set of teeth 214 on the gear rack 210. Moreover, when aligned as shown, upon movement of the gear rack 210 translationally in the back to front motion, the set of teeth 214 will engage the gear 212 and cause the gear to rotate about the axis.
In an embodiment, the axle (not shown expressly) of the gear 212 may be fixed with respect to a position in or adjacent to the thermal block 204. In combination with this, a guide pin 304 may be positioned within aperture 302 and the axis of the guide pin 302 may be fixed to a portion of the thermocycler device 200 beneath the thermal block 204. By fixing the guide pin 304 relative to the fixed axle of the gear 212, the gear rack 210 may be secured vertically in place with the set of teeth 214 positioned to engage the gear 212. Additionally, inasmuch as the guide pin 304 facilitates the translational movement and horizontal stability of the gear rack 210, the guide pin 304 may further have an outer profile that matches the profile shape of the inner wall surface of the aperture 302. For example, as depicted, an outer end (304 (a), see
To effectuate the actual lifting force on the labware 300, a rotary cam 306 may be connected to an inner facing surface of the gear 212 (or connected to the axle thereof) so as to cause the rotary cam 306 to rotate as well. Furthermore, a lifting pin 308 may extend from the rotary cam 306. In an embodiment, the lifting pin 308 is disposed offset from the axis of the gear 210 and/or the rotary cam 306. Further, the lifting pin 308 may extend inwardly toward the thermal block 204. Accordingly, when the gear rack 210 is in a first position (e.g., a rearward or shifted laterally rearward, where the lid 206 is closed and the labware 300 is on the thermal block 204), the lifting pin 308 rests in a slot 310. The slot 310 may be defined in a lateral (or otherwise adjacent) edge of the thermal block 204, which is below the upper surface of the thermal block 204 and beneath the labware 300 (see
Notably, in an embodiment having more than one set of corresponding elements of the apparatus 202 (i.e., more than one gear, rotary cam, lifting pin, set of teeth, aperture, and guide pin), a lateral distance 312 between the apertures, gears, rotary cams, lifting pins, sets of teeth, and/or guide pins may be determined so that the gears operate in a staggered timing when the gear rack is moved. As such, the lifting force would also be staggered with each lifting pin being lifted at a different time. An advantage that may occur is that by staggering individual rotary cams in time, a first portion of the labware 300 is engaged slightly prior to the second (or more) portions, which facilitates a gentler levering of the labware 300 from the thermal block 204. That is, staggering the force applied in the manner described above allows all of the applied mechanism force to act against a smaller number of wells (the part of the labware 300 that is adhering from the thermal activity) near the surface, instead of having to break all of the wells' adhesions to the thermal block 204 all at once. Therefore, this gradual approach generally results in a less violent release of the labware 300 and better preservation of sample integrity.
Additionally, and/or alternatively, it is contemplated that the apparatus 202 may function to separate the labware from the thermal block 204 without using gears at all. For example, in an embodiment not shown, a separation apparatus may include a “lifting” bar—pinned to the thermocycler similarly as the gear rack 210 described above, but without teeth—with one or more protrusions that extend from the lifting bar to be positioned near the underside of the labware. Such a lifting bar may be shifted to force the protrusions up against the labware through the thermal block and induce separation. This may be accomplished either manually after opening the lid of the thermocycler, or via the actuation of opening of the lid. For example, by way of providing either a lever attached to the force transfer bar (if manually) or by using linkage bars connected to the lid, a different type of mechanical structure may provide a lifting force between the labware and the thermal block 204.
In an additional and/or alternative embodiment, the apparatus 202 may be configured to perform a “wiggle” procedure during the opening of the lid 206. For example, while the above embodiments may describe a more continuously driven upward disengagement, a wiggle procedure may be more variable in direction such that the separation occurs by an alternating process of lifting and lowering the labware to ease it up more carefully. In an embodiment, the wiggle procedure may be implemented so as to gradually engage in a constant contact state to lift/lower the labware, at a gradually increasing rate (i.e., lifting up+x mm/msec, then lowering down-x mm/msec; where x is a predetermined value). Alternatively, in another embodiment, the wiggle procedure may be implemented to lift/lower the labware at a variable rate (i.e., lifting up+x mm/msec, then lowering down-y mm/msec; where x and y are different predetermined values). In such an embodiment, the lighter nudge on the labware 300 may be more advantageous than attempting to drive the lifting pin 308 continuously. That is, the wiggle procedure may allow more gradual engagement with the labware 300 while accounting for potential positioning tolerances of each thermocycler and labware 300. Accordingly, this approach may induce a lighter and more gradual release of the labware 300, while minimizing sudden pops when dealing with very stuck labware.
For a non-limiting example, a wiggle procedure may involve:
The preceding description has been provided to enable others skilled in the art to best utilize various aspects of the example embodiments disclosed herein. This example description is not intended to be exhaustive or to be limited to any precise form disclosed. Many modifications and variations are possible without departing from the spirit and scope of the present disclosure. The embodiments disclosed herein should be considered in all respects illustrative and not restrictive. Reference should be made to the appended claims and their equivalents in determining the scope of the present disclosure.
Unless otherwise noted, the terms “connected to” and “coupled to” (and their derivatives), as used in the specification and claims, are to be construed as permitting both direct and/or indirect (i.e., via other elements or components) connection. In addition, the terms “a” or “an,” as used in the specification and claims, are to be construed as meaning “at least one of.” Finally, for ease of use, the terms “including” and “having” (and their derivatives), as used in the specification and claims, are interchangeable with and have the same meaning as the word “comprising.”
