Chemistry: molecular biology and microbiology – Apparatus – Including measuring or testing
Reexamination Certificate
2001-04-24
2003-11-25
Redding, David A. (Department: 1744)
Chemistry: molecular biology and microbiology
Apparatus
Including measuring or testing
C435S287300, C435S288700, C422S064000, C422S072000
Reexamination Certificate
active
06653122
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to an automated microbiological analyzer for determining the identity of an infecting microorganism in a liquid sample. More particularly, the present invention provides a centrifugal rotor containing the appropriate reagents for performing various microorganism identity determinations and adapted for use in a totally automated microbiological analyzer.
BACKGROUND OF THE INVENTION
Various types of clinical tests related to patient diagnosis and therapy can be performed by analysis of a biological sample. Biological samples containing the patient's microorganisms are taken from a patient's infections, bodily fluids or abscesses, plated, and placed in a suspension. The suspension is combined with appropriate reagents in analytical wells in test panels or arrays, incubated, and analyzed to aid in treatment of the patient. Automated biochemical analyzers have been developed to meet the needs of health care facilities and other institutions to accelerate analysis of patient samples and to improve the accuracy and reliability of assay results when compared to analysis using manual operations. However, with ever changing bacterial genera and newly discovered antibiotics, the demand for biochemical testing has increased in complexity and in volume. Because of these greater demands, taken in conjunction with the expense and scarcity of floor space within health care institutions and the pressure to provide clinical results at lower costs, it has become important to simultaneously perform various types of biochemical tests within a highly automated and compact analyzer that operates with minimal clinician attention using cost-effective techniques.
An important family of automated microbiological analyzers function as a diagnostic tool for determining the identity of an infecting microorganism and of an antibiotic effective in controlling growth of the infecting microorganism. In performing these test, identification and in vitro antimicrobic susceptibility patterns of microorganisms isolated from biological samples are ascertained. Such analyzers have historically placed selected biochemicals into a plurality of small sample test microwells in centrifugal rotors that contain different substrates, or in multi-well panels having antimicrobics in serial dilutions, depending on the type of test being performed. Identification (ID) of microorganisms and of Minimum Inhibitory Concentrations (MIC or AST) of an antibiotic effective against the microorganism are determined by monitoring changes in the test microwells. By examining the signal patterns generated in the array of microwells, both ID and MIC measurements and subsequent analysis may be performed by computer controlled microbiological analyzers to provide advantages in reproducibility, reduction in processing time, avoidance of transcription errors and standardization for all tests run in the laboratory.
In ID testing of a microorganism, a standardized dilution of the patient's microorganism sample, known as an inoculum, is first prepared in order to provide a bacterial or cellular suspension having a predetermined known concentration. This inoculum is placed in an analytical test array or panel having a number of microwells or alternately into a cuvette rotor assembly having a central inoculum receiving chamber from which sample is distributed by centrifugal force to a number of test microwells or chambers located at the periphery of the rotor. The test wells contain predetermined identification media typically consisting of enzyme substrates, which, depending on the species of microorganism present, will exhibit color changes, increases in turbidity or changes in fluorescence after incubation. For instance, a bacterial genera may be identified on the basis of pH changes, its ability to utilize different carbon compounds, or growth in the presence of antimicrobial agents in a test well. Some tests require addition of reagents to detect products of bacterial metabolism while others are self-indicating. In conventional chromogenic panels, the inoculum is incubated some 18-24 hours before analysis is completed. Alternately, microorganism ID may be accomplished using rapid fluorogenic test arrays employing growth-independent means in which preformed enzyme substrates are placed in the test wells and fluorogenic tests based on the detection of hydrolysis of fluorogenic substrates, pH changes following substrate utilization, production of specific metabolic substrates and the rate of production of specific metabolic byproducts are made after about 2 hours of incubation. In both cases, by examining the reaction, or lack thereof, of the inoculum and reagents after incubation and over a period of time and comparing that reaction with that of known species, the types of microorganisms can be identified. Importantly, a large number of different substrates or other reagents must be available in ID testing of an unknown microorganism because the microorganism will be more or less different sensitive to different substrates and reagents. In an automated analyzer, this is achieved by providing a variety of ID test panels, each pre-loaded with substrates and reagents that are selected to produce a known pattern of measurable reaction signals for various microorganisms.
Important challenges that must be taken into consideration when designing automated biochemical analyzers that can quickly and cost-effectively perform ID biochemical tests include the volume of reagents required per test and the cost of a ID test panel, array or other device like a centrifugal ID test rotor. Because they are small and may be produced using mass-production, plastic injection molding techniques, it is advantageous to use small sized test devices having a large number of micro-liter sized microwells for performing ID tests in order to facilitate automatic handling and minimize the expense of the ID test device. Centrifugal ID test rotors like that of the present invention typically consist of a plurality of microwells that function as reaction vessels or microwells arrayed near the periphery of a generally flat disk in which the above mentioned ID biochemical tests are conducted. An aliquot of a patient's sample is placed in each microwell along with appropriate biochemical reagents, after which the rotors is generally incubated at a controlled temperature for a period of time so that an observable reaction between the sample and reagents occurs. At predetermined time intervals, each microwell of the ID rotor is examined for an indication of changes in color change, turbidity, or other observable reaction result. The pattern of changes may then be compared with reaction signal patterns of known microorganisms enabling the identification of the any microorganism within the sample, as discussed above.
Cost-effectively providing ID test devices with the required substrates and/or reagents to perform physician requested ID tests presents technical challenges that are made increasingly difficult as the numbers of the available ID substrates and/or reagents are increased. Efforts have been made to address these challenges along with other problems and some of these employ a centrifugally activated microwell filling process using an ID rotor having a large number of micro-sized channels radially connecting the test microwells to a supply reservoir near the center of the rotor. Reagents and/or test samples are placed within the supply reservoir and moved by centrifugal force through the microchannels to the test microwells.
Typical of these rotors are those described in U.S. Pat. Nos. 4,123,173, 3,555,284 and 4,387,164. While satisfactory for their intended purposes these rotors do not fulfill all the needs that exist for a small disposable rotor that is capable of accurately providing many tests on a single sample. These rotors are comprised of two disk-like rigid plastic pieces secured together to form a closed rotor. The lower disk has a central hub for mounting on a rotor drive shaft and comprises a fl
Farina Edward Francis
Gebrian Peter Louis
Gemmell Bruce McLean
Haddad Antoine Elias
Kaminski Edward Stephen
Dade MicroScan Inc.
Jordan Leland K.
Redding David A.
LandOfFree
Indentification test device in a random access... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Indentification test device in a random access..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Indentification test device in a random access... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3140676