PCR sample handling device

Details PCR sample handling device PCR sample handling device

2001-07-03

2003-02-04

Redding, David A. (Department: 1744)

Chemistry: molecular biology and microbiology

Apparatus

Including condition or time responsive control means

C435S287200, C435S288400, C435S288700, C435S809000, C435S810000, C422S050000, C422S105000, C422S105000

Reexamination Certificate

active

06514750

ABSTRACT:

BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to apparatus for handling microcracks used for performing polymerase chain reactions (PCR), for example, and, more particularly, to a device for positioning such microcards in relation to a PCR instrument.
2. Description of the Related Art
A substrate for simultaneously testing a large number of analytes, which has a small sample size and a large number of detection chambers, has been described in published PCT International Application, WO97/36681, assigned to the assignee of the present application, the disclosure of which is incorporated herein by reference. Also, in commonly assigned U.S. patent application Ser. No. 09/549,382, filed Apr. 13, 2000, now U.S. Pat. No. 6,272,939, the complete disclosure of which is incorporated by reference, a further development of a card-like substrate member having a plurality of sample detection chambers is disclosed together with a system for filling the member with a liquid sample to react with reagents located in the sample detection chambers during thermal cycling of a PCR process. Such card-like substrate members are a spatial variant of the microtiter plate and are referred to hereinafter as “microcards.” However, the microcards are often referred to in the art as “consumables” because they are relatively inexpensive and disposable after use, and as such, may be made from a variety of different materials and may assume different shapes and sizes.
Microcards typically contain 96, 384, or more, individual sample chambers, each having a volume of about 1.0 &mgr;L or less in a card size of 7 cm×11 cm×0.2 cm, for example. Although both the number of sample chambers and the volume size of the individual sample chambers may vary widely, the relatively small size of the microcards present problems in transporting them into and out of a PCR instrument, such as instrument models 7700 or 7900 HTavailable from Applied Biosystems of Foster City, Calif., and aligning the microcard with a thermal cycling block and an optical system in the PCR instrument.
Handling, including placing and removing microcards into and from thermal cyclers of a PCR instrument, storing, and transporting of the microcards may be accomplished either manually or robotically. A robot typically functions by gripping the sides of the microcard by “fingers”, or grips. Because a microcard may have a relatively thin body, with side edges as thin as 0.5 mm or less in thickness, robotic handling may become impractical or inconsistent, especially when multiple microcards are stacked together. Additionally, to accomplish real time PCR processing the microcard must be aligned with an optical reading device, such as a CCD or laser scanner. To be effective, such alignment requires high precision usually greater than tolerances provided by the edges of the microcard. There is a need for reliable alignment of a microcard with a scanner, camera, or luminometer of a PCR instrument.
In addition to the problems associated with alignment, PCR processing requires uniform and complete contact of the sample chambers of the microcard with a thermal cycling block of a PCR instrument. In some instances, where the microcard is formed by laminated plastic materials, there is a tendency for warpage of the card from an initial planar configuration. Thus, to ensure complete contact of the sample chambers of the microcard with the surface of the thermal cycling block, a flexing of the microcard is required so that is conforms to the typically planar surface of that block. In other instances, the microcard may be formed of flexible material incapable, in itself, to maintain a shape that conforms to the surface of the thermal cycling block. In positioning the latter types of microcards relative to the thermal cycling block of a PCR instrument, therefore, provision must be made to conform the microcard to the surface of the thermal cycling block.
Thus, it will be appreciated that there is a need for improvements in apparatus for positioning microcards of the types mentioned above in relation to a PCR instrument, and to facilitate handling of such microcards in general.
SUMMARY OF THE INVENTION
The advantages and purpose of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. The advantages and purpose of the invention will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims.
To attain the advantages and in accordance with the purpose of the invention, as embodied and broadly described herein, the invention is directed to a device for handling PCR microcards, each having an array of sample chambers closed by a transparent material on one side thereof, in relation to a PCR instrument. The device includes a carrier having an apertured region with an array of holes corresponding in number and relative location with the array of sample chambers in each of the microcards, and a structure for retaining a microcard on the carrier so that the transparent material faces the apertured region with the sample chambers aligned, respectively, with the holes in the apertured region, and so that the side of the microcard opposite the transparent material is unobstructed at least throughout the array of sample chambers. Also structure is provided for positioning the microcard retained on the carrier in relation to the PCR instrument.
In another aspect, the advantages and purpose of the invention are attained by such a device having a carrier plate including the apertured region, and a peripherally closed retention frame having an opening at least as large as the array of sample chambers and being fitted to the carrier to retain the microcard in relation to the carrier plate.
In yet another aspect, the advantages and purpose of the invention are attained by such a device for a microcard that has through-holes in marginal portions thereof outside the array of sample chambers, a plate member including the apertured region, and pins projecting from the plate member outside of the apertured region to engage in the through-holes in the marginal areas of the microcard.
In a further aspect, the advantages and purpose of the invention are attained by a PCR kit including at least one handling device, a supply of microcards, and optionally, the appropriate thermal block for processing the supplied microcard. Other kits might include microcards filled with reagents of a supplier's design or custom reagents ordered by a customer. The appropriate handling device would be included with the filled microcards.
It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention, as claimed.


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