1. Field of the Invention
The present invention relates to a system and method for optically monitoring the concentration of a gas in a sample vial using photothermal spectroscopy to detect the presence of sample growth. More particularly, the present invention relates to a system and method employing an excitation source, such as a diode laser, which is used to excite gas, such as carbon dioxide, in a sample vial to create a gas lens in the sample vial, and an interrogation source, such as another diode laser, which emits light through the gas lens to a detector which measures the degree that the light is refracted by the gas lens to determine the concentration of the gas in the sample vial, which is representative of microorganism growth in the sample vial.
2. Description of the Related Art
Many medical diagnoses require that a fluid sample, such as a blood sample, be taken from a patient, cultured in a growth medium, and then examined for the presence of a pathogen believed to be causing the patient""s illness. The growth medium provides nutrients that allow the pathogen, such as a bacteria, virus, mycobacteria, mammalian cells or the like, to multiply to a sufficient number so that their presence can be detected.
In some cases, the pathogen can multiply to a large enough number so that it can be detected visually. For example, a portion of the culture can be placed on a microscope slide, and visually examined to detect for the presence of a pathogen of interest.
Alternatively, the presence of a pathogen or other organism can be detected indirectly by detecting for the presence of byproducts given off by the microorganism during its growth. For example, certain microorganisms such as mammalian cells, insect cells, bacteria, viruses, mycobacteria and fungi consume oxygen during their growth and life cycle. As the number of microorganisms increases in the sample culture, they naturally consume more oxygen. Furthermore, these oxygen consuming organisms typically release carbon dioxide as a metabolic byproduct. Accordingly, as the number of organisms present increases, the volume of carbon dioxide that they collectively release likewise increases.
Several methods exist for detecting the presence of carbon dioxide in a sample to determine whether organisms are present in the sample. For example, an instrument known as the Bactec(copyright) 9050 manufactured by Becton Dickinson and Company detects for the change in color of an indicator to determine whether carbon dioxide is present in a sample. That is, each sample is collected in a respective sample vial containing an indicator medium having a chemical that reacts in the presence of carbon dioxide to change color. A light sensor detects the color of the indicator medium in the sample vial when the sample vial is loaded into the instrument. If the sample contains an organism which emits carbon dioxide, the reflected or fluorescent intensity of the indicator medium will change in response to the presence of carbon dioxide. The light sensor will therefore detect this change in intensity, and the instrument will thus indicate to an operator that an organism is present in the sample contained in the sample vial. Other examples of instruments for detecting the presence of organisms in a sample by detecting for the change in carbon dioxide in the sample are described in U.S. Pat. Nos. 4,945,060, 5,164,796, 5,094,955 and 5,217,876, the entire contents of each of these patents are incorporated herein by reference.
Alternatively, instead of detecting for the presence of carbon dioxide to detect the presence of an oxygen consuming microorganism, it is possible to detect for a depletion in the concentration of oxygen in the sample of interest. In such a system, the sample vial includes an indicator whose color or fluorescence changes as the concentration of oxygen in the vial changes. This change in color or fluorescence can be detected by an instrument, which can provide an indication to a technician that oxygen in the sample is being depleted by an oxygen consuming organism within the sample. An instrument employing this oxygen detecting technique is described in U.S. Pat. No. 5,567,598, the entire contents of which are incorporated herein by reference.
The presence of oxygen consuming organisms can also be detected by detecting for a change in pressure in a sealed sample vial containing the sample of interest. That is, as oxygen in a closed sample vial is depleted by oxygen consuming organisms, the pressure in the sealed sample vial will change. The pressure will further change in the sample vial as the organisms emit carbon dioxide. Therefore, the presence of such organisms can be detected by monitoring for a change in pressure in the closed sample vial. Instruments that are capable of detecting changes in pressure in the sample vial are described in U.S. Pat. Nos. 4,152,213, 5,310,658, 5,856,175 and 5,863,752, the entire contents of each of these patents are incorporated herein by reference.
It is noted that the techniques described above each detect for the presence of oxygen or carbon dioxide in a sample vial by detecting the change in a state or condition of an indicator other than the oxygen or carbon dioxide itself. For example, certain of the techniques detect for a change in color of an indicator, while others detect for a physical change, such as the movement of a diaphragm which indicates a change in pressure. These techniques can therefore be susceptible to erroneous results if, for example, the indicators themselves are inaccurate.
Accordingly, to avoid such errors, detection probes or sensors can be inserted directly into the sample vial to detect for the presence of carbon dioxide or oxygen directly. An instrument for detecting for the presence of carbon dioxide in a sample directly is described in U.S. Pat. No. 4,971,900, the entire contents of which are incorporated herein by reference. This probe technique, however, is an invasive technique which requires that a sensor or probe be inserted directly into the sample vial containing the sample. This technique can prove hazardous because the probes can become contaminated with the organism present in the sample. Moreover, when the probes are being inserted into or removed from the vial, the potentially hazardous organisms can escape into the atmosphere, thus endangering the technician or others in the general vicinity of the instrument.
Techniques have therefore been developed which are capable of detecting the presence of, for example, carbon dioxide without the need for detecting a change in the condition of an indicator, and without the use of an invasive detector or probe. In one technique, infrared light is irradiated through the sample vial containing the sample of interest. The infrared light passing through the sample vial is detected by an infrared detector. Because carbon dioxide absorbs infrared light within a certain wavelength range, if any carbon dioxide is present in the sample vial, infrared light within that particular wavelength range will be absorbed by the carbon dioxide and thus not be detected by the infrared detector. The signals from the infrared detector are analyzed to determine whether any of the infrared light being emitted into the sample vial is absorbed and thus not detected by the infrared detector. If any absorption has occurred, the instrument provides an indication that carbon dioxide is present in the sample vial, and thus, a carbon dioxide producing organism is likely present. Examples of instruments which perform this type of technique are described in U.S. Pat. Nos. 5,155,019, 5,482,842 and 5,427,920, the entire contents of each are incorporated by reference herein.
The infrared light detecting technique has advantages over the technique described above which uses an invasive detector or probe, because the technique reduces the possibility of contamination. Furthermore, because the infrared light technique directly detects for the presence of carbon dioxide instead of detecting for a change in an indicator, more accurate results can be attained. However, the infrared light technique has certain disadvantages. For example, carbon dioxide absorbs infrared light within a somewhat wide range of wavelength, which can also be absorbed by other gases. Hence, if gases in the vial other than carbon dioxide absorb some of the infrared light, the instrument may provide a false indication that carbon dioxide is present Accordingly, the accuracy of the infrared light technique described in the patents referenced above is somewhat limited.
A need therefore exists for an improved non-invasive system and method for detecting for the presence of oxygen or carbon dioxide in a culture sample, to thus detect for the presence of an oxygen consuming or carbon dioxide producing organism in the sample.
An object of the present invention is to provide an improved system and method for optically monitoring the concentration of a gas in a sample vial to detect the presence of sample growth.
Another object of the present invention is to provide a system and method employing photothermal spectroscopy to monitor the concentration of a gas, such as oxygen or carbon dioxide, or the concentration of a liquid or solid, in the sample vial to thus detect for microorganism growth in the sample vial based on the monitored concentration.
A further object of the present invention is to provide a system and method capable of housing and incubating multiple sample vials containing respective samples, and optically monitoring the concentration of a medium in each of the sample vials by photothermal spectroscopy to detect the presence of sample growth in the vials based on the respective monitored concentrations.
These and other objects are substantially achieved by providing a system and method for monitoring the concentration of a medium in at least one container. The medium can be a gas, such as oxygen or carbon dioxide, or a solid or liquid. The system and method each employs an energy emitting device, such as a laser or any other suitable type of light emitting device, which is adapted to emit a first energy signal toward a location in the container. The first energy signal has a wavelength that is substantially equal to a wavelength at which the medium absorbs the first energy signal so that absorption of the first energy signal changes a refractive index of a portion of the medium.
The system and method each also employs a second energy emitting device, adapted to emit a second energy signal toward the portion of the medium while the refractive index of the portion or portion of an adjoining medium is changed by the first energy signal, and a detector, adapted to detect a portion of the second energy signal that passes through the portion of the medium or adjoining medium. The system and method each further employs a signal analyzer, adapted to analyze the detected portion of the second energy signal to determine an amount of a sample in the container based on a concentration of the medium in the container. In particular, the signal analyzer can analyze the detection portion of the second energy signal to determine whether the sample includes an organism which consumes or emits the medium.
USPTO Backgrounds
USPTO Backgrounds