US-12616975-B2 - Thermoblock for receiving and regulating the temperature of at least one laboratory specimen vessel, method of production and simulation method

US12616975B2US 12616975 B2US12616975 B2US 12616975B2US-12616975-B2

Abstract

The invention relates to a thermoblock for receiving and regulating the temperature of at least one laboratory specimen vessel in a laboratory temperature regulation device, more particularly in a PCR thermocycler, wherein the thermoblock has been produced by means of an additive manufacturing method using a material containing metal. The invention further relates to a method for producing the thermoblock and a computer-implemented method for the simulation of physical characteristics of the thermoblock to be produced in accordance with the invention.

Inventors

Malte Kirsch-Rösner
Florian Dürr
Henner Tasch
Thore Höper
Manuel Petzold

Assignees

EPPENDORF SE

Dates

Publication Date: 20260505
Application Date: 20201202
Priority Date: 20191203

Claims (11)

1 . A thermoblock for receiving and controlling the temperature of at least one laboratory sample container in a laboratory temperature control device, particularly in a PCR thermocycler, characterized in that the thermoblock comprises: a base plate having a first plate side configured for thermal coupling with a temperature control device and a second plate side opposite the first plate side, the second plate side being provided with a plurality of sample container receptacles for receiving and controlling the temperature of a plurality of laboratory sample containers, the plurality of sample container receptacles being arranged in a rectangular grid, and connecting portions which are arranged above the base plate and connect neighboring sample container receptacles of the plurality of sample container receptacles, the thermoblock including the base plate, the plurality of sample container receptacles, and the connecting portions, being manufactured by means of an additive manufacturing process using a metal-containing material.
2 . The thermoblock as set forth in claim 1 , comprising a multiplicity of sample container receptacles manufactured by means of the additive manufacturing process for receiving and controlling the temperature of a multiplicity of laboratory sample containers.
3 . The thermoblock as set forth in claim 1 , comprising at least one sample container receptacle which was manufactured by means of the additive manufacturing process and which is cup-shaped, particularly at least in the form of a hollow cone.
4 . The thermoblock as set forth in claim 3 , wherein at least one sample container receptacle has an opening for receiving the laboratory sample container as well as a foot portion situated opposite the opening that is integrally connected to the plate portion and was manufactured by means of the additive manufacturing process, the volume of the material of the foot portion decreasing upward starting from the base portion.
5 . The thermoblock as set forth in claim 1 , comprising a base portion and at least one sample container receptacle connected thereto having an opening for receiving the sample container and a wall portion that is arranged between the opening and the base portion, an interior surface of the wall portion is set up for thermal coupling to the laboratory sample container arranged in the sample container receptacle, the wall portion particularly comprising a lower wall subportion, a wall thickness of which is greater than a wall thickness of a wall subportion that is arranged above the same.
6 . The thermoblock as set forth in claim 1 , comprising the base plate that extends parallel to a plane arranged horizontally and at least two adjacent sample container receptacles connected thereto, with at least one, or precisely one, connecting portion extending parallel to the plane being present between the at least two adjacent sample container receptacles, particularly between a plurality of or all immediately adjacent sample container receptacles.
7 . The thermoblock as set forth in claim 6 , wherein there is a void between the connecting portion and the base plate, and wherein said connecting portion is not directly connected to the base plate.
8 . The thermoblock as set forth in claim 6 , wherein there is no void between the connecting portion and the base plate, and/or wherein said connecting portion is directly connected to the base plate.
9 . The thermoblock as set forth in claim 1 , which has been manufactured integrally from a granulate containing aluminum or an aluminum alloy by means of the additive manufacturing process.
10 . The thermoblock as set forth in claim 1 , which, after the manufacture thereof by means of the additive manufacturing process, has been processed by a secondary processing method, particularly by heating, coating, polishing, and/or chip-removing treatment.
11 . A laboratory device, particularly a PCR thermocycler, containing a thermoblock as set forth in claim 1 .

Description

This application is a Section 371 national phase filing of PCT Application No. PCT/EP2020/084235, filed on Dec. 2, 2020, and titled THERMOBLOCK FOR RECEIVING AND REGULATING THE TEMPERATURE OF AT LEAST ONE LABORATORY SPECIMEN VESSEL, METHOD OF PRODUCTION AND SIMULATION METHOD, which claims priority to European Patent Application No. 19213186.0, filed on Dec. 3, 2019, each of which is incorporated herein by reference in its entirety. The present invention relates to a thermoblock for receiving and controlling the temperature of at least one laboratory sample container, particularly a multiplicity of laboratory sample containers, in a laboratory temperature control device, particularly in a PCR thermocycler. The invention also relates to a method for manufacturing a thermoblock and to a computer-implemented method for simulating physical properties of the thermoblock to be manufactured according to the invention. Such thermoblocks are used particularly in thermocyclers that are intended for PCR (polymerase chain reaction). Thermocyclers are laboratory temperature control devices in which liquid samples are heated or cooled to specific temperature levels in temperature cycles. Peltier elements that are thermally coupled to the underside of the block are generally used for temperature regulation (temperature control). A temperature cycle consists of at least two—in the case of PCR often two or three—temperature levels, which are set according to a predetermined protocol and maintained for the desired duration. The temperature cycles are repeated many times successively in order to obtain the desired result, particularly the amplification of a DNA or DNA sequence. In the case of PCR, typical temperature levels of a temperature cycle are 55° C., 70° C., and 95° C. The optimum temperature levels for a specific amplification reaction can deviate from the three temperature values mentioned. The optimal temperature levels can be determined by applying a temperature gradient in a thermoblock, so that a variation of temperature levels can be simultaneously generated in the thermoblock. In the case of a PCR, for example, the optimal temperature of a temperature level is that temperature which—in combination with the other optimal temperature levels that are required—leads to the maximum yield of the amplified product. The efficiency of a thermocycler or a thermoblock is measured, among other things, by the precision with which the temperature level is maintained. If, for example, a multiplicity of identical samples are heated simultaneously in a laboratory sample container in a thermoblock, it is desirable in most cases that the same temperature be set precisely in each laboratory sample container, e.g., the corresponding sample well of a PCR plate, and particularly also for the same duration. Given this objective, it is necessary that, for a given heating or cooling capacity of the temperature control devices acting on the thermoblock, maximally homogeneous temperature distribution in the thermoblock be achieved at the same time. One well-known source of temperature inhomogeneity in the thermoblock is the lateral edge regions of the thermoblock, which are more exposed to the ambient temperature from the lateral direction than the center of the block. If a thermoblock is temperature-controlled from below by means of Peltier elements, the temperatures measured in the sample container receptacles in the edge region deviate from the temperatures measured in the sample container receptacles in the center of the block. Some thermocycler manufacturers therefore work with additional temperature control devices that are arranged in the edge region and are intended to compensate for the environmental effects. This results in corresponding additional effort and expense in the production and maintenance of corresponding thermocyclers. What is more, good temperature homogeneity can be achieved if the necessary heat flows are enabled in all regions of the thermoblock and efficient temperature control is promoted particularly in the edge regions of the thermoblock. The influence of the ambient temperature can also be minimized if the thermoblock has the highest possible specific heat capacity. These requirements are satisfied by thermoblocks made of solid metal, typically aluminum, in which the sample container receptacles as well as the additional desired external shape are produced by chip-removing manufacturing processes. The solid construction of such blocks leads to a high specific heat capacity and homogeneity. On the other hand, the high specific heat capacity also leads to a slow change in the temperature level and thus to a long overall process time for cyclic temperature control programs carried out with the thermoblock, as well as to higher energy consumption. The chip-removing manufacturing process also limits the possibilities for optimizing the block structure. An alternative method for manufacturing a silver block is to