Spiral System Instruments, Inc.

Spiral Biotech, Inc.

Exotech Limited

Spinal Systems Inc.

Spiral Systems Instruments, Inc.

Samuel Schalkowsky

William Pepper, Jr

Donald Whitley

Frances M Scher

Leon G Hunt

Ellen R Schalkowsky

Louis L Clipp

A method for measuring the combined bactericidal and bacteriostatic effects of an antimicrobial agent on the number of viable cells in a bacterial population exposed to an application-relevant concentration of the agent, with the rate of change of the number of viable cells as a function of different exposure intervals expressed on a per-drug-free division interval g.sub.0 (generation time) basis, so as to facilitate the assessment of projected therapeutic efficacy independent of the particular generation time used in the test environment. (2) A method for measuring the combined bactericidal and bacteriostatic effects of an antimicrobial agent on the acceleration of viable population change at a concentration corresponding to the Discrete Minimal Inhibitory Concentration (DMIC), when the size of the initial viable population remains essentially unchanged in the presence of the agent. (3) A method for measuring the bactericidal component of the effect of an antimicrobial agent from measurements of the initial viable population deposited on nutrient agar media and the number of visible colonies which formed from this deposit in the presence of a selected concentration of the antimicrobial agent. (4) A method for determining the value of the DMIC, and the rate of change of bactericidal activity with changing concentrations of the antimicrobial agent, by applying the method of (3) above at different concentrations of the antimicrobial agent; computing the probability of successful cell division from colony count data at the selected concentrations of the antimicrobial agent; evaluating the functional relationship between the probabilities of division and concentration of the agent; and obtaining from this function the value of the DMIC, the Minimum Cidal Concentration (MCC) where bactericidal activity begins and the rate of change of bactericidal activity with drug concentration.

Method for measuring the bactericidal and bacteriostatic effects of

A method and apparatus for cleaning the sample delivery stylus tubing of spiral platers to prevent the carry over of disinfectants or microbes to succeeding samples by maintaining working levels of liquids in the containers to within prescribed limits so as to assure the cleaning of the stylus relative to a defined depth of immersion in the preceding cleaning or sample intake station. Containers are marked to identify the minimum required and maximum allowable levels, providing the basis for the timing and amount of liquid to be replenished. To minimize the frequency of replenishments, a digital (microprocessor implemented) control is used to avoid the use of excess liquids, beyond that needed to assure effective cleaning.

Method and apparatus for cleaning the sample delivery stylus of

A method for evaluating the comparative effect of growth-affecting substances, such as antimicrobial drugs or antibiotics, on different cultures of microorganisms is disclosed. The cultures are plated on the surface of a culture medium (12), such as agar, in adjacent at least partially separated tracks, such as tracks formed as Archimedes spirals. The cultures may be different concentrations of the same microbe or a test culture and a reference culture. The growth-affecting substances (22) are placed in contact with the culture medium on which the cultures have been plated preferably in the form of disks containing a powdered growth-affecting substance which dissolves and diffuses differentially into the culture medium to produce zones (24) of inhibition of growth extending radially outward from the disk. A comparison of the distance between the disk and the point of inhibition of the tracks of the different cultures which intersect the disk permits direct measurement of the comparative effects of the growth-affecting substance.

Method for testing the comparative effect of growth-affecting substances

A method for determining an interacting culture medium concentration IAC of a growth-affecting substance in a volume of the culture medium related to growth of a microbial population deposited on a surface of the culture medium in accordance with the invention includes the steps of depositing the growth-affecting substance at a selected stock concentration SC in a programmed deposition on the surface of the culture medium such that the volume of the stock concentration at any deposited location on the surface of the culture medium is determinable; determining a transformation function TF which accounts for movement of the deposited growth-affecting substance through the culture medium; and calculating IAC as a function of SC and TF.

Processor implemented method for determining the potency of a growth

The present invention is an improved system for counting of bacterial colonies on a plate. The system permits the counting of colonies under adverse colony counting conditions where there is overlap of colonies and analyzes the plate in a plurality of segments. The colony counts for each segment are subjected to count correction, size qualification and distribution qualification to correct for missed counts and to eliminate data from the system data base when the count for a segment will not produce reliable data. The entire plate is also analyzed for subsample qualification which provides the best estimate of the bacteria containing liquid which was used to produce the colonies as represented by a coefficient of variation of the bacterial density in the liquid.

Computer assisted biological assay system

A method and apparatus for calculating the growth interacting substance potency and growth ratio for the intersections of a scanning spot with a track of visible microbial colonies on an interaction plate. The potency is a measure of the weight of a growth interacting substance which is deposited on the interaction plate per unit volume of the growth culture medium. The growth ratio is a measure of the growth interacting substance effect on growth of colonies of microbes on the interaction plate along the path of interaction of the scanning spot with visible microbial colonies.

Method and apparatus for testing microbial interaction with growth

A method for testing microbial interaction with growth affecting substances. A pattern of a microbe containing solution is applied on an interaction plate in a programmed concentration. A solution of a growth interacting substance is applied on the interaction plate in a programmed potency in a pattern which contacts the microbe containing solution to cause contact of the microbes with the growth interacting substance. The resultant plate is incubated for a time sufficient to produce visible microbial colonies on the interaction plate. The potency of a growth interacting substance is determined at any point of interest on the incubated interaction plate by correlating the position of the point of interest with the programmed volume of the growth interacting substance deposited at that point.

Method for testing microbial interaction with growth affecting substances

An apparatus for making dilutions of a sample with a diluent to a predetermined dilution factor f by weight of the diluent is disclosed. A scale with TARE capability produces an output signal of the weight W of a sample within a container less the weight of the container. A dilution factor control is provided for setting the predetermined dilution factor f. Means are provided for calculating and storing the value TW=W/f which is the total weight of the sample plus the weight of the diluent which is required to dilute the sample to the predetermined dilution factor f. A pump is connected between a reservoir of diluent and the container for the sample for pumping the amount of diluent into the container which is required to dilute the sample to the predetermined weight dilution factor f. The scale provides a continuous output of the weight W of the sample plus diluent in the container at any instant in time. Means are provided for calculating when TW-W=0. In one embodiment, the flow of diluent to the container is stopped by the stopping of the pump when TW-W=0. In another embodiment, the flow of diluent to the container is stopped by closing a pair of valves located between the pump and the container when TW-W=0.

Gravimetric diluter

An instrument and method for applying high pressures of short duration, with very little temperature rise in the sample, to disrupt tissue, kill cells, etc., is described. The instrument uses an accelerating piston to apply a strong impact upon a sample contained in a chamber capable of holding the very high pressures produced. Following the chamber is a nozzle section. The nozzle has a receiving end cap with an impact surface and a receiver extension which can vary the distance between the nozzle exit and the impact surface. Depending upon the acceleration of the piston and sample size, a portion of the sample emerges from the nozzle as a hypervelocity jet while the remainder stays in the nozzle. The part of the sample remaining in the nozzle will have been subjected to the pressures built up by the shock wave created when the piston strikes the sample seal. The part of the sample which emerges as a jet will have been subjected to the shock pressures and, in addition, will have been subjected to high shear and decompression forces and to a jet stagnation pressure which represents the pressure exerted by the jet when it impacts the impact surface.

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Chevy Chase, MD, United States of America

Samuel Schalkowsky