Optics: measuring and testing – For size of particles – By particle light scattering
Reexamination Certificate
2000-04-26
2003-06-03
Font, Frank G. (Department: 2877)
Optics: measuring and testing
For size of particles
By particle light scattering
C356S338000, C356S337000, C356S342000, C356S343000
Reexamination Certificate
active
06573991
ABSTRACT:
CROSS REFERENCE TO RELATED APPLICATIONS
Not applicable.
BACKGROUND
1. Field of the Invention
The present invention relates generally to methods and devices for determining properties of a medium using radiation sensors that are compensated for component drift and changes in radiation coupling to the medium. A specific embodiment of the invention relates to biomass monitoring, where radiation scattering is used to measure the concentration of cells or microorganisms in liquid cultures.
2. Description of Prior Art
i. Compensated Radiation Sensors
Radiation sensors are widely used in the analysis of material properties. In particular, the absorption and scattering of radiation, measured by means of a radiation sensor, can be related to the concentration of a particular material within a mixture. Such measurements can be made rapidly and free from the risk of consuming, infecting, or damaging the material being analyzed. Some examples of commercial applications of optical radiation sensors are: smoke detectors, stack emission sensors, tissue oxygenation sensors, and biomass monitors in liquid cultures of cells or microorganisms.
Two common difficulties with radiation sensors that have been addressed in prior art, but not adequately resolved in combination, are sensor drift and limited dynamic range. Drift of sensor response can result from of any of the following: (1) a change in source intensity, (2) a change in detector sensitivity, and (3) a change in the efficiency of radiation coupling between the sensor and the sample. As radiation sources and detectors age, their respective output and sensitivity inevitably change. These aging effects can lead to inaccuracy in the determination of the property of the material being analyzed. The third source of sensor drift can be particularly prevalent in sensors that monitor harsh, dirty, or biologically active environments such as in the above examples of stack emission monitoring and biomass monitoring of liquid cultures. In both of these examples, accumulation of matter on the surface of the sensor can lead to drift or inaccurate readings of the sensor.
The dynamic range of material properties that can be measured by many radiation sensors is limited by the non-linear relationship between concentration of the material and attenuation of the radiation. For differing concentrations of an absorbing or scattering material of interest, the radiation level impinging upon the sensor will vary widely; high concentrations of material will greatly attenuate the radiation compared to low concentrations. For this reason, sensors that measure the transmission of radiation through a single fixed path length of material will have an inherently narrow dynamic range over which material properties can be measured.
U.S. Pat. No. 3,976,891—Parkinson discloses a sensor for smoke detection that compensates for changes in the optical coupling efficiency between the sensor and medium of interest by comparing the light transmitted through two different path lengths of air to two different detectors. The disadvantage of this method is that it provides no compensation for light source or detector drift. Further, the dynamic range of the measurement is limited by its reliance on only light transmittance to determine smoke density.
U.S. Pat. No. 4,981,362—deJong discloses a particle concentration measuring method employing a single light source and detector. Light is transmitted from the source to the detector through a movable window. By computing the ratio of the light transmitted through the window at two different path length settings, light source, detector, and optical coupling drift are partially compensated. However, any instrumental drift that occurs between the two measurements will not be compensated. Another disadvantage of this method is that it requires the use of a moving part whose mechanical motion and physical manufacture must be highly reproducible in order to compare measurements made at different times or with different devices. This method also suffers from limited dynamic range due to reliance on only light transmittance to determine particle concentration.
U.S. Pat. No. 5,617,212—Stuart describes an apparatus for open-path gas monitoring that measures transmission of light between two sources and two detectors. The second source is for calibration purposes only and does not pass through the sample. Likewise, the second detector is used only for calibration and measures light from the two sources that does not pass through the samples. This method provides the advantage of compensating for light source and detector drift. However, it does not provide compensation for changes in optical coupling efficiency between the sensor and sample. In addition, this method suffers from both limited sensitivity and dynamic range due its use of only light transmittance to measure the gas density.
U.S. Pat. No. 5,497,769—Gratton describes a sensor employing multiple light sources and a single detector. U.S. Pat. No. 5,529,065—Tsuchiya describes a sensor employing a single light source and multiple detectors. Both patents describe the measurement of light diffusely reflected from highly scattering materials. The disadvantage of these methods is that they require frequent re-calibration to compensate for light source and detector drift. In addition these methods are prone to error due to changes in the optical coupling efficiency between the sensor and sample.
U.S. Pat. Nos. 4,017,193—Loiterman and U.S. Pat. No. 5,482,842—Berndt, and European Patent Application 0945100A1—Hueber describe sensors employing two light sources and two detectors arranged to provide a pair of equal-length long paths and a pair of equal-length short paths between light sources and detectors. The four signals provided by these four combinations of sources and detectors are combined in a manner that compensates for drift in light source intensity, detector sensitivity, and efficiency of optical coupling between the sensor and the sample. The methods described by Loiterman and Berndt involve transmitting light through gaseous materials and detecting the extent of scattering or absorption, respectively. The method described by Hueber involves the detection of diffusely reflected light from a highly scattering medium such as tissue. The critical disadvantage of all three of these methods is the limited dynamic range over which material properties can be measured due to the geometric constraint that there be only two unique path lengths between light sources and detectors.
ii. Measurement of Biomass in Liquid Cultures
Liquid cultures of cells or microorganisms are frequently grown for research purposes or for commercial gain. Cells or microorganisms can be genetically modified to produce high yields of chemicals that may be difficult, expensive, or impossible to synthesize by other means. In order to prevent growth of other undesirable cells or microorganisms in the same liquid culture, it is important that the culture be grown under sterile conditions. For this reason, the growth medium is sterilized prior to inoculation with the desired cell or microorganism. In order to maintain a barrier to foreign organisms and optimize the growth of the desired cell or microorganism, liquid cultures are frequently grown under highly controlled conditions in what are referred to as fermenters or bioreactors. In addition to maintaining sterile conditions, fermenters may provide control over such parameters as temperature, pH, rate of stirring, and concentration of nutrients and dissolved gases.
Cells or microorganisms typically undergo several stages of growth in a fermenter. After inoculation, the initial growth rate of the cells or microorganisms may be slow, as the organism becomes accustomed to the new environment. This is frequently followed by a rapid growth phase where the biomass increases nearly exponentially. This growth period is sometimes referred to as the “log phase” due to the fact that the change in the logarithm of biomass is nearly linear with time. Eventually, as the nutrient supply
Debreczeny Martin Paul
Kasapi Athanasios
O'Neil Michael Patrick
Font Frank G.
Punnoose Roy M.
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