WO2007021461A1 - A system for optically analyzing a substance - Google Patents
A system for optically analyzing a substance Download PDFInfo
- Publication number
- WO2007021461A1 WO2007021461A1 PCT/US2006/028671 US2006028671W WO2007021461A1 WO 2007021461 A1 WO2007021461 A1 WO 2007021461A1 US 2006028671 W US2006028671 W US 2006028671W WO 2007021461 A1 WO2007021461 A1 WO 2007021461A1
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- WIPO (PCT)
- Prior art keywords
- wavelength
- light source
- analyte
- wavelength light
- light sources
- Prior art date
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Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/255—Details, e.g. use of specially adapted sources, lighting or optical systems
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/251—Colorimeters; Construction thereof
- G01N21/253—Colorimeters; Construction thereof for batch operation, i.e. multisample apparatus
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- G—PHYSICS
- G02—OPTICS
- G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
- G02B6/00—Light guides; Structural details of arrangements comprising light guides and other optical elements, e.g. couplings
- G02B6/0001—Light guides; Structural details of arrangements comprising light guides and other optical elements, e.g. couplings specially adapted for lighting devices or systems
- G02B6/0005—Light guides; Structural details of arrangements comprising light guides and other optical elements, e.g. couplings specially adapted for lighting devices or systems the light guides being of the fibre type
- G02B6/0008—Light guides; Structural details of arrangements comprising light guides and other optical elements, e.g. couplings specially adapted for lighting devices or systems the light guides being of the fibre type the light being emitted at the end of the fibre
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2201/00—Features of devices classified in G01N21/00
- G01N2201/06—Illumination; Optics
- G01N2201/062—LED's
- G01N2201/0627—Use of several LED's for spectral resolution
Definitions
- Fluid analysis systems traditionally use a number of components, including a light source, a wavelength selection system, a sample presentation system, and a detection system to analyze a patient's fluids.
- a light source e.g., a laser beam
- a wavelength selection system e.g., a laser beam
- a sample presentation system e.g., a liquid crystal display
- a detection system e.g., a liquid crystal display system
- each of these components sometimes add prohibitive cost to the overall fluid analysis system, thereby limiting the ownership of traditional fluid analysis systems to large clinics and laboratories.
- a system for optically analyzing a substance includes a light source having a plurality of selectable single-wavelength light sources coupled thereto, a substance presentation member optically coupled to the light source, and an optical detection system associated with the substance presentation member.
- a method for using a light source carousel having a plurality of selectable single- wavelength light sources coupled thereto includes selecting a desired single- wavelength light source from the plurality of selectable single-wavelength light sources, illuminating an analyte-containing region with the desired single- wavelength light source, and detecting a wavelength associated with the illuminated analyte-containing region.
- FIG. 1 is a simple block diagram illustrating the components of a fluid analysis system, according to one exemplary embodiment.
- FIG. 2a illustrates a perspective view of a fluid analysis system, according to one exemplary embodiment.
- FIG. 2b illustrates a perspective view of a fluid analysis system, according to one exemplary embodiment.
- FIGS. 3a and 3b illustrate perspective views of various configurations of light source and wavelength selection systems, according to various exemplary embodiments.
- FIG. 4 illustrates a side view of a micro-fluidic coupon being analyzed, according to one exemplary embodiment.
- FIG. 5 illustrates a side view of a light delivery system configuration, according to one exemplary embodiment.
- FIG. 6 illustrates a side view of a light delivery system configuration, according to one exemplary embodiment.
- FIG. 7 is a flow chart illustrating a method for analyzing a fluid with a fluid analysis system, according to one exemplary embodiment.
- FIG. 8 is a chart illustrating an analyte absorption or emission spectra and a corresponding emission spectrum of a single-wavelength light source according to one exemplary embodiment.
- the present specification discloses an exemplary system and method for completing an optical analysis on a millimeter or microliter scale volume of fluid. More specifically, according to one exemplary embodiment, a multi-wavelength selector structure having multiple single-wavelength light sources such as light emitting diodes (LEDs) or lasers is described. Numerous details of the multi-wavelength selector structure having multiple light sources, as well as an exemplary system that may incorporate the multi-wavelength selector structure will be provided below.
- LEDs light emitting diodes
- the term "light” will be meant to be understood as any electromagnetic radiation with a wavelength ranging from infrared to ultraviolet.
- the term “analyte” shall be interpreted broadly as referring to any compound or substance chosen to undergo analysis by the present exemplary system and method. Additionally, as used herein, the term “analyte” shall also be interpreted broadly as including any number of analyte reaction chemistries configured to enhance analysis by the present system and method, regardless of whether the analyte reaction chemistries include the originally identified analyte.
- single-wavelength light source shall be interpreted broadly to include any number of light sources having a seemingly narrow wavelength spectrum.
- a single-wavelength light source shall include any light source that, while technically polychromatic, is sufficiently narrow with respect to an analyte or chromophore absorption or emission spectrum to provide a quantifiable chemical analysis.
- the seemingly narrow wavelength spectrum of a light emitting diode (LED) shall be interpreted herein as a single-wavelength light source.
- FIG. 1 A fluid analysis system (100) incorporating a multi-wavelength selector structure with multiple single-wavelength light sources is illustrated in FIG. 1 , according to one exemplary embodiment.
- the present fluid analysis system (100) includes a single unit configured to function as a light source and wavelength selection system (110), a sample presentation system (120), and a signal detection system (130).
- prior art fluid analysis systems include multiple complex and high priced components such as independent light sources such as xenon strobes or tungsten lamps, a wavelength selection system such as filters or monochromators, an analyte sample presentation system such as a glass or polymer cuvette or a well plate that accommodates an analyte test volume of approximately 200 to 10,000 microliters, and a sample detection system including expensive photomultiplier tubes.
- the present combination light source and wavelength selection system effectively eliminates the expensive filters or monochromaters incorporated by traditional fluid analysis systems, thereby reducing the overall cost of the present fluid analysis system (100), while efficiently and elegantly providing desired wavelengths for analysis. Further details of the present fluid analysis system (100) will be provided below with reference to FIGS. 3 through 8.
- FIG. 2a illustrates a detailed perspective view of a fluid analysis system, according to one exemplary embodiment.
- the exemplary fluid analysis system (100) includes a light and wavelength selection system (110) including a light generating carousel (220) having a plurality of single- wavelength light sources (225) coupled thereto.
- a servo mechanism (210) may be operationally coupled to the light carousel (220).
- a processor (200) may be controllably coupled to the servo mechanism (210), according to one exemplary embodiment. Also illustrated in the exemplary fluid analysis system (100) of FIG.
- an analyte-containing fluid may be presented to the light and wavelength selection system (110) by a sample presentation system (120) such as a biofluid coupon with cuvettes about the perimeter.
- a sample presentation system 120
- the analyte detection system 130
- the analyte detection system may include an optical sensor (230) communicatively coupled to an amplifier (240) and to the processor (200). Further details of the exemplary fluid analysis system (100) will be provided in detail below.
- the combination light source and wavelength selection system (110) may include a number of components including, but in no way limited to, a processor (200), a servo mechanism (210), and a light generating carousel (220).
- the light generating carousel (220) may comprise a substantially disk shaped support member having a plurality of single- wavelength light sources (225) coupled to the perimeter thereof.
- the disk shaped support member hosting the plurality of single-wavelength light sources (225) may be formed of any number of materials including, but in no way limited to, a metal, a polymer, and/or a composite.
- the light generating carousel (220) may include any number of single-wavelength light sources (225) that may be selectively oriented to illuminate a desired analyte.
- the single-wavelength light sources (225) may be any number of single-wavelength light sources including, but in no way limited to, light emitting diodes (LEDs) and/or micro-lasers. LEDs are extremely durable, having lifetimes in the tens of thousands of hours. Use of the selectively oriented single-wavelength light sources allows the light generating carousel (220) to be designed to provide illumination in any number of desired wavelengths to a desired analyte-containing region on the sample presentation system (120).
- the light generating carousel (220) may include an array of individual LEDs that emit light ranging in wavelength from 350 to 960 nm. According to one exemplary embodiment, the mentioned wavelength range may be accomplished with a carousel of LEDs. Consequently, coverage of the visible spectrum, plus near UV and near IR, where the vast majority of common analytes, tagged, and un-tagged chromophores display absorption or emission features, may be accomplished at lower costs than traditional light sources. [0028] According to the exemplary embodiment illustrated in FIG. 2a, the light generating carousel (220) may be disposed adjacent to the sample presentation system (120) in a generally parallel plane as the sample presentation system.
- the rotational axes of the sample presentation system (120) and the light generating carousel (220) are substantially parallel and offset such that the outer edges of the sample presentation system and the light generating carousel (220) are slightly overlapped.
- the single-wavelength light sources (225) may be selectively rotated to be disposed above the sample presentation system (120). Consequently, the single- wavelength light sources (225) of the light generating carousel (220) generate a desired wavelength of light that may then be passed through an analyte- containing fluid contained on the sample presentation system (120), such as a micro-fluidic disk, and onto the optical sensor (230).
- an analyte- containing fluid contained on the sample presentation system (120) such as a micro-fluidic disk
- the light generating carousel (220) rotates the appropriate single-wavelength light source (225), such as an LED, into position. This allows light with a wavelength characteristic substantially matching that of an absorption or emission feature of the analyte-containing solution of interest to pass through the sample of analyte contained in the micro-fluidic disk (120).
- the ability to selectively rotate the light generating carousel (220) provides the ability to measure many analyte-containing solutions that require different illumination wavelengths to match their absorption or emission spectra on a single sample presentation system (120) such as a micro-fluidic disk.
- FIG. 2a illustrates a light generating carousel configuration including a light generating carousel having a plurality of single-wavelength light sources (225) disposed on the periphery thereof.
- the axis of the light generating carousel (220) is concentric with the axis of the sample presentation system (120) having multiple sources.
- FIGS. 3a and 3b illustrate two alternative light generating carousel shapes.
- the light generating carousel (300) may include a disk shaped member (310) with a number of single-wavelength light sources (225) disposed on the outer periphery thereof such that the single-wavelength light sources may emit light in a radial direction from the disk shaped member (310).
- the light generating carousel (300) may be selectively rotated from an axis at the center of the disk (330), as illustrated by the arrow in FIG. 3a.
- the light generating carousel (300) may be oriented perpendicular to a sample presentation system (120) such as a micro- fluidic disk containing a desired analyte. According to this exemplary embodiment, the light generating carousel (300) may be selectively rotated to provide a desired single-wavelength light source (225) adjacent to the desired analyte-containing region for analysis.
- the light generating member may assume a non- disk shape as illustrated in FIG. 3b.
- the light generating member (350) may include a polygonal shaped member (360) having a number of single-wavelength light sources (225) disposed thereon in a substantially linear array.
- the polygonal shaped light generating member (350) may be linearly translated, as indicated by the arrow of FIG. 3b, to selectively dispose the single-wavelength light source (225) adjacent to a desired analyte- containing region.
- the polygonal shaped light generating member may be oriented tangential to the outer periphery of a disk shaped sample presentation system (120).
- the polygonal shaped light generating member (350) may be associated with sample presentation systems (120) of various shapes, including, but in no way limited to a polygonal shaped sample presentation system (120).
- the light and wavelength selection system (110) also includes a servo mechanism (210) configured to selectively orient the single-wavelength light sources (225) adjacent to the sample presentation system (120).
- the servo mechanism (210) may include any number or combination of a stepper/servo motor system, a shaft system, a belt system, a gear system, and the like.
- the servo mechanism (210) incorporated by the light and wavelength selection system (110) may be rotational and/or translational to correspond with the sample presentation device (120).
- Use of the servo mechanism in conjunction with a light generating carousel provides testing speed, accuracy, and functionality.
- the processor (200) that is controllably coupled to the servo mechanism (210), shown in FIG. 2a, may be configured to control the selective positioning of the light generating carousel (220) relative to the analyte position of the sample presentation system.
- a desired light source (225) configured to generate a desired wavelength, corresponding to an analyte, may be identified using a program hosted by the processor (200). That identified light source (225) may then be converted into servo instructions that are then housed in a processor readable medium (not shown).
- the instructions housed in the processor readable medium may be used to control the servo mechanisms (210), thereby selectively positioning the light generating carousel (220).
- the processor (200) illustrated in FIG. 2a may be, but is in no way limited to, a micro-controller, a workstation, a personal computer, a laptop, a personal digital assistant (PDA), or any other processor containing device.
- an exemplary sample presentation system (120) is illustrated in the form of a biofluid coupon with cuvettes about the perimeter. While a disk-shaped biofluid coupon is illustrated as an exemplary sample presentation system (120) in FIG. 2a, any number of sample presentation systems having various geometries may be incorporated in the present exemplary fluid analysis system (100). Specifically, the sample presentation system may be rectangular, elliptical, circular, or any other geometry, as is known in the art. According to the exemplary embodiment illustrated in FIG.
- the disk shape biofluid coupon with cuvettes located about the perimeter, configured to function as a sample presentation system (120) may include a circular disk disposed on a rotating central spindle, or alternatively, the sample presentation system may include a rectangular coupon which may have one or two axis linear motion. According to the exemplary embodiment illustrated in FIG. 2a, the sample presentation system (120) may also be controllably coupled to the processor (200) for controlling movement thereof.
- the sample presentation system (120) may include cuvettes for housing the desired analyte-containing fluid.
- the cuvettes may be glass or plastic vials with flat smooth sides that permit absorbance measurements on the contents of the vial.
- the disk may be made from transparent polymethylmethacrylate.
- the volume of the vial may vary including volumes in the tens of microliters and even to as low as the single microliter range or less.
- the sample presentation system (120) may include any number of microfluidic coupons with capillary or pneumatic channels for moving fluids.
- sample presentation system (120) may include any number of mechanisms, channels, active valves, passive valves, syringes, and or pipettes configured to aid in the mixing or dilution of the desired analyte-containing solution with reagents.
- the sample presentation system (120) may include a rotating disk containing micro-fluidic channels where chemical reactions involving the analyte may be performed by inertial mixing etc. Additionally, a counter-rotating light generating carousel (220) containing an array of LEDs or other identified light source (225) located at the periphery may be disposed just above the micro-fluidic disk and slightly overlapping it. At the periphery of the sample presentation system disk (120) are located "cuvettes" where the isolated analyte or chromophore containing solution may be located.
- an identified "cuvette” would be the LED or other light source (225) of the appropriate wavelength, its light passing through the cuvette and onto an analyte detection system (130).
- the light generating carousel (220) rotates the appropriate light source (225) into position. This allows light with a wavelength characteristic substantially matching that of an absorption or emission feature of the analyte-containing solution of interest to pass through the sample of analyte contained in the micro-fluidic disk (120).
- This light generating carousel (220) provides the fluid analysis system (100) with the ability to measure a panel of analytes that each require a different wavelength to match their absorption or emission spectra, on a single sample presentation system (120).
- a signal detection system (130) is also associated with the present fluid analysis system (100).
- the signal detection system (130) may include an optical sensor (230) communicatively coupled to a signal amplifier (240).
- the signal detection system (130) is configured to sense characteristics of analytes or analyte chemical reaction products in the sample presentation system (120).
- the optical sensor (230) may be any optical sensor configured to sense the characteristics of the light incident on, passing through, reflected by, or fluoresced from the analyte or analyte chemical reaction.
- the optical sensor (230) may include, but is in no way limited to, a photodiode, a photocell, or charge coupled device (CCD).
- CCD charge coupled device
- the term "charge coupled device” or “CCD” is meant to be understood as referring to any light- sensitive integrated circuit that stores and displays data for an image in such a way that each pixel (picture element) in the image is converted into an electrical charge, the intensity of which is related to the amount of light falling on the device.
- the sensitivity of available optical sensors (230) such as CCDs and photodiodes allow for analysis of analytes on the microliter volume scale, i.e. pathlengths and areas in the single millimeter range.
- CCDs are configured to store and display received light in such a way that each pixel of received light is converted into an electrical charge, the intensity of which is related the amount of light falling on the device. Consequently, a relatively large CCD may be positioned under a plurality of cuvettes to simultaneously receive light associated with multiple analytes.
- the CCD or other optical sensor (230) may also be positioned away from the cuvettes and the light from multiple analytes transferred to the CCD with lenses, fiber optics, light pipes, or other mechanisms.
- the light that reaches the optical sensor (230) passes from a light source (225), through an analyte disposed on the sample presentation system (120), to the optical sensor (230).
- a light source 225
- an analyte disposed on the sample presentation system (120)
- the light generating carousel (220) containing a number of single-wavelength light sources (225) selectively positions the single-wavelength light sources such that the light may pass through the desired analyte and on to an optical sensor without the use of additional optical components.
- an optical configuration (400) may include a number of single-wavelength light sources (225), such as LEDs, linearly arranged over a measurement zone such as an analyte or analyte-derived chromophore (440) contained in a cuvette (430). Since each single-wavelength light source (225) is focused onto the cuvette and the signal collected by the photodetector for analyte testing, the single-wavelength light sources (225) may be channeled. As illustrated in FIG. 4, the single wavelength light (450) generated by the single-wavelength light source (225) may be channeled to a single emission zone with the use of a lightpipe (410).
- single-wavelength light sources such as LEDs
- the lightpipe (410) may include any number of hollow cylinders having a substantially reflective inner surface or optical fiber having a high degree of total internal reflection.
- the exemplary optical configuration (400) may include any number of focusing optics (420) configured to focus the generated single- wavelength light (450). Once the single-wavelength light (450) has been channeled to an analyte, the light goes through the analyte and excites an analyte or chromophore, such as fluorophore, and the subsequent emission of light is detected perpendicular to the incoming light to maximize the desired signal relative to incident and stray light.
- analyte or chromophore such as fluorophore
- an exemplary fluid analysis system (500) illustrated in FIG. 6 shows the single-wavelength light sources (225) may be arrayed above a plurality of cuvettes (430) containing a desired analyte or analyte-derived chromophore (440).
- the signals passing through the analytes or chromophores (440) of the various cuvettes (430) are then routed to the photodetector by individual optical fibers (610).
- the individual sources (225) may be selected to provide optical communication between the desired single- wavelength light sources (225) and the optical sensor (230).
- the optical sensor may be configured to detect any number of wavelength characteristics of the analyte or analyte-derived chromophore including, but in no way limited to, absorption or emission, fluorescence, chemilluminescence, and combinations thereof. Positioning the detector perpendicular to the incoming light is often preferred for sensitive fluorescence and chemilluminescence measurements. Detectors used in this mode may require filtering for optimal signal quality, as illustrated in FIG. 4. Regardless of the optical sensor incorporated into the exemplary fluid analysis system (400), the detection of light by the optical sensor (230) is converted into an electrical charge. The weak electrical charge generated by the optical sensor (230) may then be passed through a signal amplifier (130) before being transmitted to the processor (200), as illustrated in FIGS. 2a and 2b.
- a signal amplifier 130
- the electrical signal may then be analyzed for wavelength characteristics of the analyte reaction chemistry.
- the absorbance of a desired analyte reaction chemistry may be determined according to Beer's Law as illustrated by the following formula:
- the absorbance (A) equals the molar extinction coefficient (D) multiplied by the absorption or emission path length ⁇ ) and the chromophore concentration (c).
- the absorption or emission path length (600) of the analyte or analyte-derived chromophore (440) may be known according to the size of the cuvette (430).
- the extinction coefficient (D) of the analyte or analyte-derived chromophore may be ascertained by the processor (200; FIG. 2a) from a lookup table, according to one exemplary embodiment. Once the above-mentioned characteristics are determined and/or measured, the concentration (c) of the analyte may be computed.
- FIG. 7 illustrates an exemplary method for using the above- mentioned fluid analysis system (100), according to one exemplary embodiment.
- the present exemplary method begins by first providing an analyte sample adjacent to the light source and wavelength selection system (step 700).
- the analyte sample may be provided adjacent to the light source and wavelength selection system (110; FIG. 1) in any number of forms and using any number of analyte presentation devices.
- the analyte sample may be provided adjacent to the light source and wavelength selection system using a biofluid coupon with cuvettes formed about the perimeter.
- a desired wavelength may be selected (step 710).
- the desired wavelength for the single-wavelength light source may be selected based, at least in part, on the anticipated absorption or emission spectra of the analyte reaction chemistry of the analyte being tested.
- an absorption or emission spectra is displayed (800) illustrating the characteristics of both an analyte (810) and a single-wavelength light source (820).
- the analyte absorption or emission spectrum includes at least one peak.
- the LED emission spectrum (820) exhibits a peak associated with its radiation wavelength.
- one particular light source may exhibit an emission peak corresponding with peaks in the analyte absorption or emission spectrum.
- the sample analyte or analyte reaction chemistry may then be illuminated by a single-wavelength light source radiating the identified wavelength (step 720). More particularly, according to one exemplary embodiment, once the desired wavelength is identified by the processor (200; FIG. 2a) or the operator, the light generating carousel (220) may be controllably maneuvered, via the servo mechanism (210), to orient a desired single-wavelength light source (225) adjacent to the provided analyte. The single-wavelength light source (225) may then be controllably illuminated to pass a desired wavelength of light through the provided analyte.
- the analyte or analyte reaction chemistry As the analyte or analyte reaction chemistry is illuminated, light that traverses the solution may then be optically detected by the photodetector (230; FIG. 2a) and used to generate illumination data (step 730). Once the illumination data is generated, the data may be amplified and transmitted to a processor for analysis (step 740). As mentioned previously, the generated illumination data may be analyzed for any number of characteristics including, but in no way limited to, absorption or emission according to Beer's Law, as described in detail above.
- the present exemplary system and method provide a simple robust optical analysis system that reduces cost while maintaining utility and speed.
- the present multi-wavelength selector structure includes multiple single-wavelength light sources such as light emitting diodes (LEDs) or lasers, which may assume any number of structural configurations, focusing or channeling to a small area.
- LEDs light emitting diodes
- the incorporation of multiple single-wavelength light sources, in conjunction with a photodetector such as a CCD or photodiode allows multiple analytes to be measured simultaneously.
Abstract
Description
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Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
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JP2008526032A JP2009505066A (en) | 2005-08-11 | 2006-07-24 | System for optical analysis of materials |
DE112006002136T DE112006002136B4 (en) | 2005-08-11 | 2006-07-24 | A system for optically analyzing a substance |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US11/201,983 US7791728B2 (en) | 2005-08-11 | 2005-08-11 | System for optically analyzing a substance with a selected single-wavelength |
US11/201,983 | 2005-08-11 |
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WO2007021461A1 true WO2007021461A1 (en) | 2007-02-22 |
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PCT/US2006/028671 WO2007021461A1 (en) | 2005-08-11 | 2006-07-24 | A system for optically analyzing a substance |
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US (1) | US7791728B2 (en) |
JP (1) | JP2009505066A (en) |
CN (1) | CN101287980A (en) |
DE (1) | DE112006002136B4 (en) |
WO (1) | WO2007021461A1 (en) |
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CN105928893A (en) * | 2016-05-23 | 2016-09-07 | 杭州霆科生物科技有限公司 | Multi-sample multi-index micro-fluidic optical detection system |
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Also Published As
Publication number | Publication date |
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DE112006002136B4 (en) | 2010-09-23 |
DE112006002136T5 (en) | 2008-07-31 |
US20070037272A1 (en) | 2007-02-15 |
JP2009505066A (en) | 2009-02-05 |
US7791728B2 (en) | 2010-09-07 |
CN101287980A (en) | 2008-10-15 |
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