Chemistry: molecular biology and microbiology – Apparatus – Bioreactor
Reexamination Certificate
2001-04-13
2003-02-11
Beisner, William H. (Department: 1744)
Chemistry: molecular biology and microbiology
Apparatus
Bioreactor
C435S287200, C435S303100, C220S526000, C422S105000
Reexamination Certificate
active
06518060
ABSTRACT:
The invention relates to a cover pad for covering a plurality of reaction wells open to the upper surface configured in a plate-shaped body provided for implementing chemical and/or microbiological reactions such as e.g. the PCR process.
The invention is a further development of an in-house earlier development as described in the U.S. patent application THERMOCYCLER APPARATUS (application Ser. No. 09/467,322) filed on Dec. 20, 1999, now U.S. Pat. No. 6,153,426. Reference is made to this patent application in it being incorporated in the present application.
Said patent application relates to a thermocycler apparatus for implementing chemical and biological reactions in which a plate-shaped body can be accommodated comprising reaction wells open to the upper surface. This thermocycler apparatus includes a lid and a closing mechanism for locking the lid in place. An electrically signalled positioner is provided such that once the lid has been locked in place a pressure can be exerted on the reaction wells. For sealing the reaction wells it is proposed to interpose a rubber mat between the the lid and the reaction wells open to the upper surface so that the reaction wells are sealed by the rubber mat which is urged against the reaction wells by the lid.
Conventionally, the reaction wells are sealed by a film of oil or wax. This film of oil or wax is applied to the chemical mixture introduced into the reaction wells and has the task of ensuring that there is no possibility of chemical cross-contamination between neighboring reaction wells. Where chemical or biological reactions are concerned, which take place without any appreciable increase in temperature, it is expedient to apply such a film of oil or wax. Where, however, high reaction temperatures are involved or if the chemical mixture is heated, as is the case with the PCR procedure, for instance, then the oil or wax film becomes thin and no longer represents a suitable protection against chemical cross-contamination between neighboring reaction wells. More particularly, when the chemical mixture boils, the film of oil or wax fails to provide effective contamination protection.
Thus for implementing chemical or biological reactions needing to be free of contamination the reaction wells are welded with a thin film of plastics so that each and every reaction well is closed off. The reaction wells are usually configured in standardized microtitration plates. The film is welded to the microtitration plates such that an annular weld forms around each reaction well.
Providing such a film welded to the reaction wells permits implementing chemical or biological reactions free of contamination. However, prior to implementing the chemical or biological reactions the film needs to be manually welded to the reaction wells and removed manually after the chemical or biological reactions have been carried out. This is why it is hardly possibile to integrate welding such a plastics film in a fully automated system for implementing chemical or biological reactions.
U.S. Pat. No. 5,604,130 describes a pad for covering multi-well plates. This pad is a stiff planar element or a flexible polymer sheet. This polymer sheet may be made of various flexible polymeric materials, e.g. rubber, silicone rubber, polyurethane rubber and the like. The thickness of this sheet is stated to be in the range 0.9 mm to 1.5 mm. The flexible polymer sheet cannot be handled with an automated apparatus since gripping a flexible sheet is very difficult. The planar stiff element is basically suitable for being handled by an automated apparatus. However, such pads prove to be very difficult to release from the reaction wells once the reaction has been implemented, resulting in a vacuum in the individual reaction wells and the apparatus concerned needing to be dimensioned correspondingly large.
Described in WO 99/61152 is another cover for microtitration plates. Shown therein is a multi-layer sheet comprising a backing layer and a sealing layer. The backing layer is stiff. It may, however, be made of a flexible material. The sealing layer is made of a non-elastically deformable material such as e.g. silicone to provide an air-tight seal. This sealing layer comprises a tacky surface so that the the cover tacks to the microtitration plate.
An apparatus for automated implementation of chemical or biological reactions is described in WO 99/26070, it being from this international patent application that the U.S. patent application with application Ser. No. 09/554,743 materialized. Reference is made to this patent application in it being incorporated in the present application.
The invention is based on the object of providing a cover pad for covering a plurality of reaction wells open to the upper surface configured in a plate-shaped body which permits facilitated repeated use in automated systems with no high force needed to lift off the cover pad.
This object of the invention is achieved by a cover pad having the features of claim 1. Advantageous aspects read from the sub-claims.
The cover pad in accordance with the invention is provided for covering a plurality of reaction wells open to the upper surface configured in a plate-shaped body provided for implementing chemical and/or microbiological reactions such as e.g. the PCR process. The cover pad is made of an elastomer, it comprising a soft backing which is provided with a backing plate for stiffening, and the backing plate is curved such that when a compressive load of at least 5 N is applied to the full surface area of the backing plate by a planar compression body the backing plate elastically conforms thereto in assuming a corresponding shape free of curvature.
After the chemical and/or microbiological reactions have been implemented, this curvature of the backing plate results in the cover pad being partially lifted off from the plate-shaped body comprising the reaction wells as soon as a pressure with which the cover pad is urged against the plate-shaped body during the chemical and/or microbiological reaction is cancelled. The backing plate is made of a material which is so stiff that even in the case of reactions, in which a vacuum materializes in the individual reaction wells, the cover pad is lifted off in part from the plate-shaped body. This ensures that no high force is needed to lift off the cover pad from the plate-shaped body even when a vacuum is created in the individual reaction wells. Since the backing plate reassumes its original curvature after the reactions have been implemented, the cover pad has already been released from the majority of the reaction wells and is held only by a few reaction wells arranged in areas at which the curved cover pad is in contact due to the vacuum existing therein. The resulting retaining force is so slight, however, that the cover pad is reliably lifted off from the plate-shaped body when lifted by a handling device.
REFERENCES:
patent: 2771399 (1956-11-01), Savage
patent: 5056427 (1991-10-01), Sakabe et al.
patent: 5282543 (1994-02-01), Picozza et al.
patent: 5604130 (1997-02-01), Warner et al.
patent: 5721136 (1998-02-01), Finney et al.
patent: 5851492 (1998-12-01), Blattner
patent: 6153426 (2000-11-01), Heimberg
patent: 9926070 (1999-05-01), None
patent: 9961152 (1999-12-01), None
Heimberg Wolfgang
Schurf Markus
Beisner William H.
MWG-Biotech AG
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