Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving viable micro-organism
Reexamination Certificate
2001-04-24
2003-11-11
Gitomer, Ralph (Department: 1651)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving viable micro-organism
C435S288500
Reexamination Certificate
active
06645737
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to methods using microbiological test arrays having a number of microwells in automated analyzers. More particularly, the present invention provides a method for maintaining the integrity of a of liquid test solution within the individual microwells.
BACKGROUND OF THE INVENTION
Various types of 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 and are typically placed in test panels or arrays, combined with various reagents, 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 facilitate 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 both complexity and in volume. Because of these greater demands 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 an antibiotic effective in controlling growth of the microorganism. In performing these test, 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 wells in panels or arrays that contain different antimicrobics against known microorganisms in serial dilutions. Minimum Inhibitory Concentrations (MIC) of antibiotics effective against the microorganism are determined by color changes, fluorescence changes, or the degree of cloudiness (turbidity) in the sample test wells created in the arrays. By examining the signal patterns generated, MIC analyses are 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.
The use of microbiological test trays and the techniques employed in MIC tests, also known as antibiotic susceptibility testing, AST, of microorganisms are also well known. AST tests are essentially broth dilution susceptibility tests using wells filled with inoculum and a growth broth, called herein a inoculum-broth solution, and increasing concentrations of a number of different antibiotics, or antimicrobial agents. The different antimicrobial agents are typically diluted in Mueller-Hinton broth with calcium and magnesium in chromogenic panels or diluted in autoclaved water with a fluorogenic compound in fluorogenic panels. The antimicrobials are diluted to concentrations that include those of clinical interest. After incubation, the turbidity or fluorescence will be less or non-existent in wells where growth has been inhibited by the antimicrobics in those wells. The analyzer compares each test well reading with a threshold value. The threshold value is a fixed number corresponding to a certain percentage of relative absorbency or fluorescence which corresponds to clinically significant growth. The MIC of each antimicrobial agent is measured either directly as visible growth, or indirectly as an increase in fluorescence.
Important challenges that must be taken into consideration when designing cost-effective, automated biochemical analyzers include the volume of reagents required per test and the cost of the disposable test panel, array or, in certain designs, a centrifugal test rotor. Because they are small and may be produced using mass-production, plastic injection molding techniques, it is advantageous to use very small sized test arrays having a number of microwells for performing AST tests in order to facilitate automatic handling and minimize the expense of a disposable test array. AST test arrays typically consist of a plurality of adjacent microwells aligned in some sort of an array that function as reaction vessels for the above mentioned biochemical reactions involving a solid phase media and a liquid phase containing a sample to be tested. An aliquot of the sample is placed in each microwell along with appropriate antibiotic reagents. AST testing usually requires that the test trays be incubated at a controlled temperature for a period of time so that an observable reaction between the sample and reagent occurs; at predetermined time intervals, each microwell of the test tray is examined for an indication of changes in color change, turbidity, or size.
Filling the number of microwells with the required inoculum and/or reagents presents several technical challenges that are made increasingly difficult as the size of the microwells is reduced. These challenges include providing a uniformity of fill, maintaining an absence of air bubbles that impede test observations, controlling adverse evaporation effects, maintaining the integrity of test observations, etc. Efforts have been made to address these challenges along with other problems and these generally employ a vacuum technique in filling microwells within a test array via an interconnected number of micro-sized channels connected between the microwells and an inoculum reservoir.
U.S. Pat. No. 5,932,177 provides a test sample card as typically used in biochemical analysis, having a number of same-sized rectangular shaped sample wells and fluid flow by means of a plurality of through-channels which route the fluid flow of samples along both the front and back surfaces of the card. Elevated bubble traps are provided, as are integral interrupt slots for sensing card position and alignment.
U.S. Pat. No. 5,922,593 discloses a microbiological test panel having a plurality of translucent cups extending from a first side of a planar surface, and a chassis having a plurality of open-ended tubes formed in the chassis. The chassis includes a plurality of raised passage walls on a second side of the planar surface that form passageways over the openings at the bottom ends of the tubes. One end of the passageway has an opening to allow an inoculum to flow through the passageway. The chassis further comprises an air communication port formed as an open-ended tube extending from the second side of the planar surface.
U.S. Pat. No. 5,766,553 discloses a molded test sample card comprising a fluid entrance port and first and second end regions and first and second side regions. A plurality of growth or reaction wells are located in the card body between the first and second end regions and the first and second side regions. A fluid channel network connects the fluid entrance port to said growth wells. To improve the flow of the material during the molding process, cored regions are disposed in at least one of the first and second end regions or the first and second side regions.
U.S. Pat. No. 5,746,980 discloses a test sample card with a fluid intake port and sample wells disposed between its opposite surfaces. A fluid channel network connects the fluid intake port to the sample wells and a bubble trap is connected to at least one of the sample wells by a conduit with formed in said first surface of the card. The bubble trap is formed as a depression extending part way through the card body and is covered by sealant tape.
U.S. Pat. No. 5,679,310 discloses a microtiter plate formed of a substantially rigid, polymeric plate having a substantially flat upper surface and a array of cylindrical or frusto-conical wells. The well bottom is either fluid impervious or pervious. In emb
Dunfee William David
Farina Edward Francis
Gemmell Bruce McLean
Kaminski Edward Stephen
Mazza John Charles
Dade Microscan Inc.
Gitomer Ralph
Jordan Leland K.
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