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Miniaturized fluorescence analysis systemMiniaturized fluorescence analysis system description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20060082768, Miniaturized fluorescence analysis system. Brief Patent Description - Full Patent Description - Patent Application Claims
CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit of U.S. Provisional Application No. 60/606,000, filed Aug. 31, 2004. BACKGROUND [0003] 1. Field [0004] Embodiments of the present invention relate to fluorescence analysis systems and in particular to light emitting diode (LED)-based fluorescence analysis systems. [0005] 2. Discussion of Related Art [0006] Fluorescence is the emission of light by molecules which have absorbed light. The fluorescing characteristics of such molecules (called fluorophors) are useful in detecting and tagging various microbiological events. The emission signal is shifted to higher wavelengths (Stokes-Shift) in relation to the excitation signal because the energy of the fluorescing light emitted is less than the light absorbed by the fluorophor. [0007] Fluorometers exploit the fluorescing property of fluorophor molecules in the analysis of biological samples. The simulation and optimization of a LED-based fluorometer should ideally maximize the efficiency with which light is converted to signal (emission) and minimize bleed-through excitation light to the output signal path. In other words, the overlap between excitation light source and emission spectra should be minimized so that once the excitation light is optically filtered from the output signal, maximum emission signal remains for measurement. [0008] Conventional fluorescence analysis systems use a laser or a high power white light source (e.g. Xenon lamp) to excite fluorophors in the sample under analysis. LEDs (light emitting diodes) are of interest to replace conventional light sources to increase the portability (reduce power, size, and weight) of the analysis system and to improve the flexibility of excitation spectra available to the user with reduced optics overhead. Several approaches have been used in LED-based fluorescence analysis systems. LEDs are an attractive alternative to conventional white light sources used in fluorescence analysis because of reduced power of operation, fewer imaging artifacts, and increased flexibility in spectral control without the need for high overhead optics. [0009] General purpose, commercially available portable systems, such as the Turner Biosystems [1][2] instruments have used single LEDs to excite fluorescing samples; these systems rely on the user to select the LED to match the fluorophor or vice versa. Many results in the literature rely on single or small arrays of LEDs, where excitation bands are chosen close to the excitation spectra of the fluorophor and the resulting emission spectrum is optically filtered to minimize interference from the excitation signal. Still other approaches excite a sample using different LEDs at different times and subsequent signal processing to improve the extraction of the emission signal from the combined output signal. Finally, a variety of waveguides have been constructed to minimize the transfer of excitation light along the output emission path at the expense of reduced sample volume. [0010] The use of LEDs, however, is often limited by three primary factors: (a) the broadband output of an LED often interferes with the measurement of emission signal; (b) the power (intensity) of light generated by an LED (mWatts) is often small compared to white light source (Watts) counterparts; and (c) the excitation peaks of the LED are often not well matched to the absorption efficiency of the fluorophor under analysis. The use of LEDs, for this reason, has been largely limited to high concentration applications where emitted fluorescence is sufficiently high (and noise sufficiently low) that LED limitations do not restrict effective measurements of the sample under analysis. The spectral flexibility, modularity, low-cost, and low power consumption of LEDs, however, continue to make them attractive options for fluorescence analysis, however. [0011] In many approaches using LEDs, the choice of LED (or LEDs) is usually not optimized prior to the collection of data by the fluorescence analysis system. Instead, the optics and signal processing are assigned the task of separating excitation components from the emission signal in the output path. In addition, many LED-based fluorescence analysis systems used in commercial and research efforts are general-purpose. This means that they are suited to a relatively wide selection of fluorophors and the biological applications to which they are applied. SUMMARY OF EMBODIMENTS OF THE INVENTION [0012] Embodiments of the present invention are directed to automated and modular optimization of fluorescence analysis system that may maximize signal extraction (SNR) from an excited fluorophor. In one embodiment, the system includes an array of light emitting diodes (LEDs) that emit excitation light. The excitation light may have a first color and/or wavelength (blue, blue-green, green, purple, or other suitable color/wavelength. The color and/or wavelength of the excitation light of one LED may be different than the color and/ or wavelength of another excitation light of one LED. [0013] The system also includes control electronics that apply drive currents to the LEDs. The drive currents cause the LEDs to emit the excitation light. The drive current to one LED may be different than the drive current to another LED. For some embodiments, the drive current is greater than nominal drive current, greater than rated maximum current for the LED, and in may range between twenty and two hundred milliamps. The control electronics may include an emitter follower circuit and/or source follower circuit to drive the LEDs. [0014] The control electronics also may pulse the drive current to the LEDs with signals having low duty cycles. For example, in one embodiment, the control electronics may pulse the drive current to the LEDs with signals having duty cycles between one percent and twelve percent. In other embodiments, the control electronics may pulse the drive current to the LEDs with signals having duty cycles at or greater than twelve percent. [0015] The system also includes optics to couple excitation light from the LEDs to a holder for the fluorophor. In one embodiment, an optical fiber bundle may be coupled to each individual LED so that each LED has its own optical fiber bundle associated with it. The optical fiber bundles may be bundled together so that the excitation light from the LEDs may be aggregated into a single light beam that has a substantially uniform intensity profile and/or a substantially uniform wavelength distribution. The bundle of bundles couples the single light beam to the fluorophor holder. In one embodiment, the optical fiber bundles are bundled together in a random manner. [0016] For some embodiments, the system may include a beam splitter to split off a small portion of the single light beam and to direct the small portion to circuitry to measure the intensity of the small portion of the single light beam as a function of the color and/or wavelength. The circuitry may adjust drive current to one or more LEDs in response to the measured intensity of the small portion of the single light beam. The circuitry may be a spectrophotometer. [0017] For other embodiments, one or more PIN diode may be coupled to one or more LEDs, respectively, to detect the excitation light emitted from the LED. There may be circuitry to adjust one or more drive currents in response to the detected excitation light. [0018] When the excitation light impinges on a fluorophor placed in the fluorophor holder, the fluorophor may emit light that in response to the excitation light. The emitted light may have a color and/or wavelength that is different than the color and/or wavelength of the excitation light. In one embodiment, the fluorophor holder may be a cuvette. [0019] The system also includes a photodetector to detect light emitted from the fluorophor. The photodetector may a photomultiplier tube, an avalanche photodiode, photodiode, phototransistor, and/or a charge-coupled device (CCD). [0020] The system also includes optical fiber to couple the light emitted from the fluorophor to the photodetector. [0021] For some embodiments, the system may be used to select a configuration for the LED array. The system may determine at least two possible permutations of LEDs for the LED array and for each permutation determine a total excitation light that is to be emitted from the LED array, determine an amount of excitation light that is to reach the fluorophor based on the total excitation light emitted from the LED array, determine an amount of light that is to be transmitted through the fluorophor based on the amount of excitation light that is to reach the fluorophor, based on an amount of attenuation in an emission path to a photodetector from the fluorophor in the fluorescence analysis system, and based on filtering of the light that is to be transmitted through the fluorophor, determine an amount of light that is to be emitted by the fluorophor based on the amount of excitation light that is to reach the fluorophor and based on the amount of light that is to be transmitted through the fluorophor, determine an amount of light that is to reach the photodetector based on the amount of light that is to be emitted by the fluorophor, and determine a leakage penalty for the fluorescence analysis system based on the amount of light that is to be transmitted through the fluorophor and based on the amount of light that is to reach the photodetector. The system then compares the leakage penalties for each permutation of LEDs in the LED array and ranks the permutations of LEDs in the LED array based on the comparison of their respective leakage penalties. [0022] In one embodiment, the system may receive from a user information associated with a type of LEDs to be selected from a database, information associated with a number of LEDs to be placed in the LED array, information associated with the fluorophor of interest, information associated with at least one undesirable fluorophor, information associated with a minimum concentration detection capability for the fluorophor of interest, and/ or information associated with a time frame within which to perform fluorescence analysis on the fluorophor of interest. Continue reading about Miniaturized fluorescence analysis system... 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