Measuring and testing – Sampler – sample handling – etc. – Analyzer supplier
Reexamination Certificate
2000-04-13
2001-08-14
Raevis, Robert (Department: 2856)
Measuring and testing
Sampler, sample handling, etc.
Analyzer supplier
Reexamination Certificate
active
06272939
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates in one aspect to liquid loading of vessels. In a particular embodiment, this invention relates to a system for filling a substrate having at least one chamber with a liquid sample, such as a system for filling a card-like member having a plurality of sample detection chambers with a liquid sample to react with reagents located in the sample detection chambers during thermal cycling of a polymerase chain reaction (PCR) process. In another aspect, the present invention relates to an apparatus for positioning a substrate in a detection unit.
2. Description of the Related Art
Biological testing has become an important tool in detecting and monitoring diseases. Recent developments in the field have spurred growth in the number of tests that are performed. Performing great numbers of these tests may be costly and time consuming. One way of minimizing costs is to reduce the size of the samples that are being tested and increase the number of samples that can be tested during each run of a thermal cycling unit or other like device. Therefore, it is often desirable to test a large number of samples having a small sample size. 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 WO97/36681, assigned to the assignee of the present application, the contents of which are hereby incorporated by reference herein.
It is desirable to provide a system for filling a substrate having a large number of small detection chambers in a manner that is safe, reliable, and fast. Previous methods require laborious steps and can expose the operator performing these steps to reagents. Moreover, previous methods may permit undue contamination between detection chambers and may be prone to the presence of air bubbles in the detection chambers. In light of the foregoing, there is a need for a system and method that overcomes the disadvantages of the previous methods.
SUMMARY OF THE INVENTION
The advantages and purposes of the invention will be set forth in part in the description which follows, and in part will be apparent from the description, or may be appreciated by practice of the invention. The advantages and purposes of the invention will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims.
In one aspect, the invention includes a system for filling a substrate having at least one chamber with a liquid sample. The system in one embodiment includes a substrate defining a network of passageways including at least one chamber for the liquid sample, and an adapter. The adapter includes a fill reservoir for the liquid sample, a vacuum port for attachment to a vacuum source, and at least two channels. One channel allows a vacuum to be imparted to the network, and the other channel allows the liquid sample to be introduced into the network. The system also includes a mechanism that sequentially closes and opens at least one of the channels so that a vacuum can first be introduced to the substrate and thereafter the liquid sample introduced to the substrate for permitting the vacuum to urge the liquid sample to flow from the fill reservoir into the substrate. The mechanism for sequentially closing and opening includes a frame that holds at least one adapter and substrate, and also includes a valving mechanism that sequentially sealingly engages and disengages the channels of the adapter.
In another aspect, the invention includes a substrate filling member configured for connection to a substrate having at least one chamber for a liquid sample. The substrate filling member in one embodiment includes a base, a reservoir on the base configured to receive a liquid sample, a vacuum port on the base configured for attachment to a vacuum source, and a plurality of fluid channels in the base. The plurality of fluid channels includes a first fluid channel for permitting a vacuum to be imparted to the substrate and at least one fluid channel of the filling member at a first setting. The plurality of fluid channels permits the liquid sample from the fill reservoir to flow into the at least one chamber of the substrate at a second setting.
In a further aspect of the invention, the invention includes a filling station for controlling the filling of substrate having at least one chamber with a liquid sample. In one embodiment, the filling station includes a base portion receiving the substrate and an adapter. The adapter includes a filling reservoir, vacuum port, and a plurality of flow paths. The filling station also includes an actuator selectively directing the liquid sample into the at least one sample chamber of the substrate when the actuator is in a predetermined position. The actuator includes a plurality of valving structures for selectively opening and closing flow paths on the adapter according to a predetermined procedure.
In a further aspect of the invention, the invention includes a method of filling at least one chamber of a substrate with a liquid sample. The method includes the step of providing a substrate having at least one chamber for containing a liquid sample and at least one path for accessing the chamber. The method further includes the step of providing an adapter for connection to the substrate, the adapter having a fill reservoir for the liquid sample, a vacuum port, and a plurality of channels. Next, a control apparatus is closed so that the substrate and adapter are fixed therein, and a liquid sample is inserted into the fill reservoir of the adapter. A vacuum is then introduced to the chamber and path of the substrate. The control apparatus is actuated in order to expose the liquid sample in the fill reservoir to the vacuum so that the liquid sample is urged towards the chamber of the substrate.
In another aspect of the invention, the invention includes an apparatus for positioning a substrate with a plurality of sample detection chambers in a detection unit. The apparatus includes a frame assembly and lens assembly. The frame assembly is configured so that a substrate may be positioned in the frame assembly. The lens assembly includes a plurality of plates. One of the plates includes a lens plate in which at least one lens is located for focusing a light which passes through the lens.
In a further aspect, the invention is a method of positioning a substrate with at least one sample detection chamber into a sample detection instrument. The method includes the steps of opening the sample detection instrument, placing a support frame on the sample detection instrument, and inserting a substrate with at least one sample detection chamber in the support frame. The method also includes placing a lens plate over the substrate and support frame, and aligning at least one hole in the lens plate relative to the sample detection chamber of the substrate. The sample detection instrument is then closed.
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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patent: 91/17239 (1991-11-01), None
patent: 97/36681 (1997-10-01), None
Landergren, U., Kaiser, R., Sanders, J. and Hood, L. “A ligase mediated gene detection technique”, 'Science 241:1077-80 (Aug. 1988).
Nickerson, D., Kaiser, R., Lappin, S., Stewart, J., Hood, L. and Landegren, U. “Automated DNA diagnostics using an ELISA-based oligonucleotide assay”, Proc. Natl. Acad. Sci USA 87:8923-27 (Aug. 1990).
Grossman, P., Bloch, W., Brinson, E., Chang, C., Eggerding, F., Fung, S., Iovannisci, D., Woo, S. and Winn-Deen, E. “High-desnity multiplex detection of nucleic acid sequences: oligonucleotide lig
Freudenthal Jacob Koppel
Frye Ward Kevin
LaBelle Terri Christina
Young Eugene
Applera Corporation
Finnegan Henderson Farabow Garrett & Dunner L.L.P.
Raevis Robert
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