Thermal cycler apparatus and related methods

Inventors

Evans, Zackery KentBodily, Thomas KnightAbbott, Richard DavidRiley, Patrick L.

Assignees

Biofire Defense LLC

Publication Number

US-11376599-B2

Publication Date

2022-07-05

Expiration Date

2031-12-02

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Abstract

An apparatus for thermal cycling can transfer heat uniformly and efficiently. The apparatus can be used in a method that reduces condensation on sample wells. The apparatus can also be manufactured to provide uniform configurations. For example, a sample illustratively for polymerase chain reaction (PCR), in each sample well and the components of the embodiment of the thermal cycler apparatus shown at including a well block, a base plate, a layer of adhesive, a peltier device, another layer of adhesive and a heat sink.

Core Innovation

The invention provides a thermal cycler apparatus comprising a well block with a plurality of wells, each well featuring an upper conical sidewall, a lower generally cylindrical sidewall, and a flat bottom. A sample well is received within each well and extends into the cylindrical section, making contact with the conical sidewall. The apparatus is designed for uniform and efficient heat transfer, using a configuration that includes a peltier device coupled to the well block and a heat sink. Layers of adhesive or alternative thermal interface materials can be used to improve thermal coupling between components.

The problem addressed by this invention arises from existing thermal cycler designs, which may not provide uniform heat distribution or efficient assembly, often requiring clamping mechanisms, and may experience condensation on sample wells during cycling. Traditional well shapes and mounting methods can result in uneven temperature distribution, inefficient cycling rates, and difficulties in automated system integration.

The described apparatus can be manufactured with consistent geometries, which enables both high heat transfer uniformity and the ability to reduce condensation on sample wells. By using a special adhesive layer, the apparatus can be assembled without conventional clamps, as the adhesive retains the peltier device even when the apparatus is turned upside down. The configuration allows for individually driven peltier devices to improve well-to-well temperature uniformity or provide temperature gradients. The system is also compatible with automated sample loading and various nucleic acid amplification procedures beyond PCR.

Claims Coverage

The patent includes two independent claims, each defining distinct inventive features focused on the structure of the well block and its integration with thermal control elements.

Thermal cycler apparatus with well block featuring flat-bottom wells

The apparatus includes: - A well block with a plurality of wells, where each well has: - An upper sidewall forming an upper conical portion - A lower sidewall forming a generally cylindrical portion below the conical portion - A flat bottom perpendicular to the cylindrical portion, forming the bottom of the interior void space, which extends continuously from the conical portion to the flat bottom - A sample well received within each interior void space and extending into at least one cylindrical portion, contacting the upper sidewall - A peltier device coupled to the well block - A heat sink coupled to the peltier device

Thermal cycler apparatus with multi-zone, individually driven peltier devices and flat-bottom well block

The apparatus includes: - A heat sink - A plurality of peltier devices thermally coupled to the heat sink - A well block having a plurality of zones of wells, each well defined by: - A proximal conical portion (conical sidewall) - A generally cylindrical portion (cylindrical sidewall) distal to the conical portion - A flat bottom perpendicular to the cylindrical portion and defining a distal end of the well - A sample well received in at least one well, with its sidewall selectively in contact with the conical sidewall and its bottom-section extending into the cylindrical portion - Each peltier device is individually driven to provide temperature uniformity to the wells

The claims cover apparatus configurations using specifically shaped well blocks (including conical and cylindrical portions with a flat bottom), integration with sample wells, and unique thermal coupling methods via peltier devices and heat sinks, including zones with individual control to enhance temperature uniformity.

Stated Advantages

Heat can be transferred uniformly and efficiently to samples.

The apparatus can reduce condensation on sample wells.

Provides uniform well block configurations that improve manufacturing consistency.

Adhesive allows assembly without clamps, enabling the device to retain the peltier device even when inverted.

Flat-bottom wells provide additional surface area, resulting in more uniform and rapid heat transfer.

Reduced well block mass from decreased well height increases thermal cycling rate.

Individually driven peltier devices enable greater well-to-well uniformity or the ability to introduce a temperature gradient.

The configuration facilitates easier automation and integration into automated systems.

Documented Applications

Polymerase chain reaction (PCR) and variations on PCR, including asymmetric PCR and post-PCR processing such as melt curve analysis.

Other amplification methods, such as strand displacement amplification (SDA), nucleic acid sequence-based amplification (NASBA), cascade rolling circle amplification (CRCA), Q beta replicase mediated amplification, isothermal and chimeric primer-initiated amplification of nucleic acids (ICAN), and transcription-mediated amplification (TMA).

Suitable for a variety of other biological and non-biological reactions that require temperature control.

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