Chemistry: electrical and wave energy – Processes and products – Electrophoresis or electro-osmosis processes and electrolyte...
Reexamination Certificate
1998-10-21
2001-04-17
Soderquist, Arlen (Department: 1743)
Chemistry: electrical and wave energy
Processes and products
Electrophoresis or electro-osmosis processes and electrolyte...
C204S602000
Reexamination Certificate
active
06217731
ABSTRACT:
FIELD OF INVENTION
This invention relates to an apparatus and method of automated capillary electrophoresis device (CED). More specifically, it relates to a computer automated CED in which a graphical user interface is provided to monitor and display various aspects of the CED.
BACKGROUND
Electrophoresis is a well-known technique for separating macromolecules. In an electrophoretic application, molecules in a sample to be tested are migrated in a medium across which a voltage potential is applied. The sample is propagated through a gel which acts as a sieving matrix to help retard and separate the individual molecules as they migrate. Oftentimes, a capillary tube (hereinafter “capillary”) is provided for holding the gel and for allowing the sample to migrate therein.
A conventional capillary electrophoresis device (CED)
10
provided with a plurality of capillaries is depicted in FIG.
1
. The conventional CED
10
includes an electrode/capillary array
11
, multilumen tubing
13
, tubing holders
15
, optical detection region
17
, capillary bundle
19
and high pressure T-fitting
21
. The capillaries have sample ends disposed in the electrode/capillary array
11
and second ends received by the high pressure T-fitting
21
.
The electrode/capillary array
11
includes electrodes and the sample ends of capillaries protruding from the bottom side of the CED. The electrodes and the sample ends of capillaries are arranged to be dipped into corresponding sample wells in a 96-well or a 384-well microtitre tray; this requires 96 or 384 capillaries in order to fully utilized every well on the microtitre tray. (The microtitre tray is not illustrated in
FIG. 1.
)
The capillaries run inside of corresponding multilumen tubes
15
which are firmly fixed in place by the tubing holders
15
. Exposed portions of the capillaries, lined up side-by-side and without the protection of multilumen tubing, then pass through the optical detection region
17
, which includes a CCD camera assembly (not shown in FIG.
1
). The CCD camera assembly captures images of samples traveling inside the exposed capillaries. The exposed second ends of the capillaries are then bundled together and fitted into the high pressure T-fitting.
The above described conventional CED is utilized to perform electrophoresis runs. An exemplary electrophoresis run may include the steps of: conditioning and preparing the capillaries by washing capillaries by injecting wash solutions to the capillaries and refilling the capillaries with gels; introducing samples to the samples ends of the capillaries when the capillaries are conditioned properly to receive the samples; applying a voltage potential, i.e., 12 KV, between the sample ends of the capillaries and the high pressure T-fitting; and capturing images of the samples as they travel inside capillaries by the CCD camera at the optical detection region. A plurality of valves and pumps are provided to the CED in order to properly carry out the washing, reconditioning and refilling cycles with appropriate liquid solutions.
More detailed description of the above features are described in U.S. patent application Ser. No. 09/105,988, which is incorporated herein in its entirety by reference.
An operator of the conventional CED, however, is required to monitor closely the CED during electrophoresis runs. For instance, liquid containers holding wash solutions to be injected into the capillaries must be checked constantly and replenished when the wash solutions are depleted. During an electrophoresis run the operator is also required to be aware of which cycle the electrophoresis run is performing, because each cycle demands the operator to perform different manual tasks. For example, after the capillaries are conditioned with the gel, the operator is required to check the sample tray and the capillaries before applying the voltage potential. This is because if sample tray is not present or if capillaries are not filled with the gel, then applying the voltage potential to the capillaries may damage the CED.
Moreover, this task of manually checking the capillaries is a laborious task, because a small impurity in the gel inserted into the capillaries or an air bubble in the capillaries can cause damage to the CED, and it may also cause the electrophoresis run to be ruined with an unusable data collection. When the samples are abundant, one unsuccessful run is not a problem; however, when the sample are rare samples then one unsuccessful run is catastrophic. In order to reduce the risk, the operator is required to check the capillaries carefully, which is time consuming and tedious. In view of the above shortcomings, what is needed is a system to automatically and monitor and regulate the CED.
BRIEF SUMMARY OF THE INVENTION
This invention provides a method and apparatus for automatic monitoring and regulating capillary electrophoresis devices. In particular, an automated electrophoresis system in accordance with the present invention comprises a plurality of capillaries configured to accommodate samples during an electrophoresis run which includes a plurality of phases; a control circuit coupled to the capillaries and configured to perform at least one of monitoring and regulating the capillaries; and a display coupled to the control circuit and configured to display corresponding information reflecting one of said monitoring and regulating of the capillaries.
The system is further provided with a computer processor coupled to the control circuit and the display. The computer processor including a input/output (I/O) interface configured to communicate with the control circuit, and a first computer memory storing a display program which displays a graphical user interface on the display. The display could be a display monitor.
In one aspect of the invention, the control circuit includes an electrical circuit configured to make electrical measurements of the capillaries. In addition, the electrical circuit comprises a plurality of resistors coupled to the capillaries, and a plurality of multiplexers configured to select one of the electrical voltages to be measured by an analog/digital converter.
In another aspect of the invention, the I/O interface is further configured to receive the electrical measurements from the control circuit, and the display program is further configured to graphically display the electrical measurements on the display monitor.
The invention is further provided with a capillary malfunction alarm configured to activate an alarm when a malfunction in at least one capillary is detected based on the electrical measurements.
In yet another aspects of the invention, the display program is further configured to continuously display the electrical measurements in real time, to graphically display instantaneous statistical variations of the electrical measurements among the capillaries, or to display a window arranged to interactively allow an operator to select a predetermined number of capillaries whose electrical measurements are to be displayed.
The display program is further configured to display a time line arranged to graphically display an identity and duration of each phase of the electrophoresis run, and an elapsed time indicator which indicates elapsed time from a start of the electrophoresis run, said elapsed time indicator comprising a graphical object which expands along the time line throughout the electrophoresis run.
The present invention is also directed to a method of controlling an electrophoresis run performed on a parallel capillary electrophoresis system which comprises a plurality of capillaries configured to accommodate samples during an electrophoresis run. The method comprises the steps of making electrical measurements of the capillaries to sense electrical conditions during the electrophoresis run and displaying information reflective of the measurements to allow an operator to monitor the electrophoresis run. The electrical measurements are made by measuring voltages across a plurality of resistors that are coupled to the capillaries.
The meth
Fields, III Robert Eugene
Kane Thomas E.
Noguerola Alex
Pennie & Edmonds LLP
Soderquist Arlen
Spectrumedix Corporation
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