US20010031502A1 - Biochip detection system - Google Patents

Biochip detection system Download PDF

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US20010031502A1
US20010031502A1 US09882912 US88291201A US2001031502A1 US 20010031502 A1 US20010031502 A1 US 20010031502A1 US 09882912 US09882912 US 09882912 US 88291201 A US88291201 A US 88291201A US 2001031502 A1 US2001031502 A1 US 2001031502A1
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light source
sample
light
sensor
configured
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US09882912
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Robert Watson
Haseeb Chaudhry
James Lee
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Alpha Innotech Corp
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Alpha Innotech Corp
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using infra-red, visible or ultra-violet light
    • G01N21/62Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64Fluorescence; Phosphorescence
    • G01N21/645Specially adapted constructive features of fluorimeters
    • G01N21/6452Individual samples arranged in a regular 2D-array, e.g. multiwell plates
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using infra-red, visible or ultra-violet light
    • G01N21/62Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64Fluorescence; Phosphorescence
    • G01N2021/6417Spectrofluorimetric devices
    • G01N2021/6419Excitation at two or more wavelengths
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using infra-red, visible or ultra-violet light
    • G01N21/62Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64Fluorescence; Phosphorescence
    • G01N21/6428Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
    • G01N2021/6439Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" with indicators, stains, dyes, tags, labels, marks
    • G01N2021/6441Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" with indicators, stains, dyes, tags, labels, marks with two or more labels

Abstract

A biochip detection system detects and locates samples that are labeled with multiple fluorescent tags and are located on a biochip. This biochip detection system includes a charge coupled device (CCD) sensor, a broad spectrum light source, a lens, a light source filter, and a sensor filter. The CCD sensor comprises two dimensional CCD arrays to simultaneously detect light waves from at least a substantial portion of the biochip. The broad spectrum light source is optically coupled to the CCD sensor and is configured to be utilized with a variety of different fluorescent tags which have differing excitation wavelengths.
The lens and the CCD sensor are optimized and matched to each other such that the sensor operates at or below the diffraction rating of the lens. Further, the resolution of the CCD sensor is matched to the samples on the biochip such that the CCD sensor oversamples each of the samples a sufficient number of times. Additionally, the lens is configured to frame at least a substantial portion of the biochip.
The biochip detection system is optimized to provide a higher dynamic range, increased sensitivity, and faster throughput compared to system utilizing laser scanners. Further, the biochip detection system is capable of utilizing a same broad spectrum light source to excite samples labeled with a variety of fluorescent tags.

Description

    FIELD OF THE INVENTION
  • The invention relates to the field of detectors for analysis of biological samples located on biochips. More particularly, the invention relates to the field of detectors that analyze samples labeled with a tag while utilizing a charge coupled device sensor. [0001]
  • BACKGROUND OF THE INVENTION
  • Detection devices that detect and locate samples contained on a biochip via laser light sources and laser scanners are well known in the art. These detection devices require that the samples be labeled by a fluorescent tag. Typically, these detection devices rely on laser light sources to excite the samples that are labeled by a fluorescent tag and causes biologically active samples to output emitted light waves. The laser source is scanned to serially excite each sample on the biochip to detect any emitted light waves from the samples that are biologically active. [0002]
  • Unfortunately, these detection devices utilizing either the laser light source or the laser scanner suffer from various drawbacks. First, laser scanners utilized to detect the emitted light waves from the exited samples on the biochip typically require wait times upwards of five minutes for sufficient resolution. Because laser scanners operate as a serial scanning device by sequentially detecting one sample at a time on the surface of the biochip, laser scanners are inherently inefficient at detecting the emitted light waves from an array of samples. [0003]
  • Further, laser light sources utilized within the detection devices inherently only emit coherent light waves which span over an extremely narrow range of wavelengths. Fluorescent tags are generally responsive to a single frequency of light or light from a narrow frequency band. Thus, the use of the laser light sources severely limits the flexibility of those detection devices because only one type of fluorescent tag can be used. To use other tags, additional laser sources must be used. Further, to evaluate a biochip that has been treated with multiple tags, the prior art's long duration scan cycle must be performed for each one of the required laser sources. [0004]
  • For example, if samples on a biochip were labeled with two different fluorescent tags and the different tags required light waves with substantially different excitation wavelengths, analyzing these samples would require the user to change laser light sources the analysis of all the samples were completed. Additionally, to be able to handle samples labeled with different fluorescent tags with differing excitation wavelengths, the user is required to have access to a variety of laser light sources. Since laser light sources are costly and specialized items, there are substantial costs and inconveniences associated with utilizing these prior detection devices. [0005]
  • Therefore, it is desirable to have an ability to detect and locate samples labeled with multiple tags contained on a biochip, without the need for a laser light source. It is also desirable have an ability to detect and locate samples labeled with a tag contained on a biochip, without the need for a serial scanning device. [0006]
  • SUMMARY OF THE INVENTION
  • The invention is a biochip detection system for detecting and locating samples that are labeled with multiple tags and are located on a biochip. This biochip detection system includes a charge coupled device (CCD) sensor, a broad spectrum light source, a lens, a light source filter, and a sensor filter. The CCD sensor comprises two dimensional CCD arrays to simultaneously detect light waves from at least a substantial portion of the biochip. The broad spectrum light source is optically coupled to the CCD sensor and is configured to be utilized with a variety of different fluorescent tags which have differing excitation wavelengths. [0007]
  • The light source filter is optically coupled between the light source and the biochip and is configured to only substantially allow light waves that have an excitation wavelength corresponding to a particular fluorescent tag to reach the biochip. The light source filter prevents light waves that have similar wavelengths to an emission wavelength of the particular fluorescent tag from reaching the biochip or the CCD sensor. The sensor filter is optically coupled between the biochip and the CCD sensor and is configured to only substantially allow light waves that have the emission wavelength corresponding to the fluorescent tag to reach the CCD sensor. The sensor filter prevents extraneous light waves from giving the CCD sensor false signals. [0008]
  • The lens and the CCD sensor are optimized and matched to each other such that the sensor operates at or below the diffraction rating of the lens. Further, the resolution of the CCD sensor is matched to the samples on the biochip such that the CCD sensor oversamples each of the samples a sufficient number of times. Additionally, the lens is configured to frame at least a substantial portion of the biochip. [0009]
  • The biochip detection system is optimized to provide a higher dynamic range, increased sensitivity, and faster throughput compared to system utilizing laser scanners. Further, the biochip detection system is capable of utilizing a same broad spectrum light source to excite samples labeled with a variety of fluorescent tags.[0010]
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • FIG. 1 illustrates a schematic side view of internal elements of the preferred embodiment of the present invention. [0011]
  • FIG. 2 illustrates a schematic side view of the preferred embodiment configured to analyze two sets of samples on a single biochip with each set of samples labeled with a different fluorescent tag. [0012]
  • FIG. 3 illustrates a schematic side view of the preferred embodiment configured to analyze a plurality of samples on a single biochip with the plurality of samples labeled with multiple fluorescent tags. [0013]
  • FIG. 4 is a graph that illustrates a relationship between a light intensity versus a wavelength of an excitation light of a particular fluorescent tag, an emitted light of this particular fluorescent tag, and the source light as utilized in the present invention. [0014]
  • FIG. 5 illustrates a top view of an external housing of an alternate embodiment. [0015]
  • FIG. 6 illustrates a side view of the external housing of the alternate embodiment. [0016]
  • FIG. 7 illustrates a perspective view of the external housing of the alternate embodiment. [0017]
  • FIG. 8 illustrates a side view of a camera housing of the preferred embodiment.[0018]
  • DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
  • FIG. 1 illustrates a side view of the preferred embodiment of the present invention. This preferred embodiment is a biochip detection system [0019] 100 as shown in FIG. 1. The biochip detection system 100 preferably includes a lens 120, a sensor filter 130, a charge coupled device (CCD) sensor 140, a light source 150, and a light source filter 160. Preferably, the biochip detection system 100 is configured to detect and locate samples 110 within a biochip 170. The samples 110 and the biochip 170 are shown for exemplary purposes only and are not intended to be part of the present invention. For the purposes of this specification, the biochip 170 is configured to have an array of samples 110 arranged in a predetermined number of rows and columns on top of a substrate. Further, the samples 110 contained within the biochip 170 are capable of including DNA or other biological material. For the biochip detection system 100 to properly operate, the samples 110 are labeled with a tag. The biochip 170 in the preferred embodiment is configured to hold samples 110 which are labeled with multiple tags. However, it will be apparent to those skilled in the art to utilize samples 110 only labeled by one tag on the biochip 170. The samples 110 in the preferred embodiment are labeled with a fluorescent tag. However, it will be apparent to those skilled in the art to substitute this fluorescent tag with a chemiluminescent tag, colormetric tag, or the like. The process of labeling samples with a tag is well known in the art.
  • The biochip detection system [0020] 100 detects and locates which ones of the plurality of samples 110 are fluorescently labeled within the biochip 170. The biochip detection system 100 operates by exciting the samples 110 labeled by a fluorescent tag with light waves having an excitation wavelength thereby generating samples 110 that emit light waves having an emitted wavelength. Next, the CCD sensor 140 simultaneously detects the light waves having the emitted wavelength from at least a portion of the biochip 170. Specific elements and procedures of the biochip detection system 100 are described in detail below.
  • The CCD sensor [0021] 140 is preferably configured to include a two dimensional array of charge coupled devices. Preferably by having the CCD sensor 140 as a two dimensional sensor, the biochip detection system 100 is capable of simultaneously imaging either an entire area or a portion of the biochip 170 (depending on the size of the biochip 170) for light waves emitted by the samples 110. By simultaneously imaging all the biochip 170, the CCD sensor 140 allows the biochip detection system 100 to complete the detection process in most cases well under one minute and in some cases in twenty-five seconds. In an alternate embodiment, the CCD sensor 140 comprises cooled charge coupled devices. By having the charge coupled devices within the CCD sensor 140 cooled, background noise is reduced and signal clarity is maximized. In this preferred embodiment, the CCD sensor 140 is manufactured by Sony Corporation having the model number ICX 038DLA. It will be apparent to those skilled in the art to utilize a different CCD sensor 140.
  • The light source [0022] 150 is preferably a broad spectrum bulb that is configured to output light waves over a wide range of wavelengths. Preferably, the light source 150 is optically coupled to the biochip 170. Because the light source 150 generates light waves over a wide range of wavelengths, the light source 150 is capable of forming light waves to excite samples labeled with a wide variety of fluorescent tags. In this preferred embodiment, the light source 150 is manufactured by General Electric Corporation having the model number 150 Watt EKE. It will be apparent to those skilled in the art to select a different light source.
  • The lens [0023] 120 is preferably a compound lens that includes multiple lens elements. The lens 120 is located in an optical path between the biochip 170 and the CCD sensor 140. Preferably, the lens 120 transmits light waves emitted from the samples 110 to the CCD sensor 140. The lens 120 is capable of adjusting and optimizing a magnification parameter such that a desired portion of the biochip 170 is captured by the CCD sensor 140 with an appropriate field of view. Preferably, the lens 120 is configured such that the CCD sensor 140 operates at or below the diffraction limit of the lens 120. In this preferred embodiment, the lens 120 is manufactured by Fujinon having a focal length of 25 millimeters and f-stop of 1:0.85. It will be apparent to those skilled in the art that the lens 120 can be substituted for a different lens or multiple lenses.
  • Preferably, the light source filter [0024] 160 is optically coupled between the light source 150 and the biochip 170. The light source filter 160 is preferably configured to substantially only allow light waves generated by the light source 150 with a predetermined excitation wavelength to reach the biochip 170. The predetermined excitation wavelength corresponds to a particular wavelength that excites one of the samples 110 that is labeled with a particular fluorescent tag. The predetermined excitation wavelength depends on the sample in conjunction with the fluorescent tag. In other words, the light source filter 160 substantially blocks all light waves from the light source 150 with wavelengths other than the predetermined excitation wavelength from reaching the biochip 170. By blocking substantially all light waves that have wavelengths other than the predetermined excitation wavelength, the light source filter 160 prevents erroneous light waves generated by the light source 150 from giving the CCD sensor 140 erroneous signals.
  • Preferably, the sensor filter [0025] 130 is optically coupled between the CCD sensor 140 and the biochip 170. As shown in FIG. 1, the sensor filter 130 is preferably between the CCD sensor 140 and the lens 120. By placing the sensor filter 130 between the lens 120 and the CCD sensor 140, the chances of distorting the light waves for detection by the CCD sensor 140 is minimized. Nevertheless, it will be apparent to those skilled in the art that the sensor filter 130 also can be configured between the lens 120 and the biochip 170. The sensor filter 130 is preferably configured to substantially only allow light waves that are emitted from a sample labeled with a particular fluorescent tag that has a predetermined emitted wavelength to reach the CCD sensor 140. The predetermined emitted wavelength occurs during excitation of this sample and depends on the sample in conjunction with the particular fluorescent tag. Preferably, the sensor filter 130 is optimized to parameters of the light source 150 and prevents extraneous light waves from reaching the CCD sensor 140 thereby increasing the accuracy and sensitivity of the biochip detection system 100. It will be apparent to those of ordinary skill in the art that the filter selection is made to correspond with the fluorescent tags and also the sample type.
  • The biochip detection system [0026] 100 is capable of efficiently detecting and locating samples 110 on the biochip 170. The CCD sensor 140 and the lens 120 are preferably optimized relative to each other and also to the samples 110 on the biochip 170. In particular, the CCD sensor 140 preferably has a transmission resolution to oversample each of the samples 110 by eight to nine times. For example, the CCD sensor 140 is preferably configured to have each of the samples 110 be optically detected by eight to nine pixels. Additionally, the lens 120 is preferably optimized to allow the CCD sensor 140 to operate at or below the diffraction limit of the lens 120.
  • In operation, the biochip detection system [0027] 100 is preferably configured to analyze the biochip 170. The samples 110 are contained within the biochip 170 and are labeled with a multiple fluorescent tags. The biochip detection system 100 initiates operation by activating the light source 150. The light waves emitted from the light source 150 are represented with a light wave 180 in FIG. 1. Next, the light wave 180 preferably passes through the light source filter 160. As the light wave 180 passes through the filter, some wavelengths of the light wave 180 are blocked. A resultant light wave after passage through the light source filter 160 is represented as a light wave 190 as shown in FIG. 1. Preferably, the light wave 190 only substantially includes light waves with a predetermined excitation wavelength which correspondingly excites the samples 110 which are labeled with the particular fluorescent tag.
  • As the samples [0028] 110 are excited by the predetermined excitation wavelength in the light wave 190, the samples 110 produce light waves which are represented by a light wave 200 as shown in FIG. 1. The light wave 200 preferably includes light waves with a predetermined emission wavelength which are produced by the samples 110. The light wave 200 then passes through the lens 120. Some extraneous light waves with the predetermined excitation wavelength also pass through the lens 120 as shown by the light wave 190. Next, the sensor filter 130 preferably blocks out substantially all light waves with wavelengths other than the predetermined emission wavelength; the sensor filter 130 substantially only allows light waves represented by the light wave 200 to reach the CCD sensor 140. By substantially allowing only light waves having the predetermined emission wavelength to reach the CCD sensor 140, the CCD sensor 140 is capable of accurately detecting and locating the samples 110 on the biochip 170. As a result, the CCD sensor 140 is prevented from erroneously detecting stray light waves.
  • The biochip detection system [0029] 100 is capable of accommodating a variety of fluorescent tags without switching the light source 150, the lens 120, or the CCD sensor 140. To utilize multiple fluorescent tags with the biochip detection system 100, only the light source filter 160 and the emission filter 130 are preferably changed. By merely changing the light source filter 160 and the sensor filter 130, the biochip detection system 100 is capable of detecting and locating the samples labeled by this new fluorescent tag. Preferably, the light source filter 160 is changed such that substantially only light waves with an excitation wavelength corresponding to a new fluorescent tag reach the samples labeled by this new fluorescent tag. Further, the sensor filter 130 is preferably changed such that substantially only light waves with an emission wavelength corresponding to the new fluorescent tag reach the CCD sensor 140.
  • FIG. 2 illustrates the biochip detection system [0030] 100 configured to analyze a biochip 210 having two sets of samples with each set of samples labeled by a different fluorescent tag. The configuration of the biochip detection system 100 which includes the light source 150, the lens 120, the sensor filters 130 and 130′, the light source filters 160 and 160′, and the CCD sensor 140 is similar to the biochip detection system 100 in FIG. 1. The sensor filters 130 and 130′ are used interchangeably, one each for detecting the presence of different fluorescent tags. The light source filters 160 and 160′ are used interchangeably to illuminate the biochip 210 with different wavelengths of light. It will be apparent to those skilled in the art that additional filters can be utilized. The biochip 210 contains a first set of samples 220 which is labeled by a first fluorescent tag, and a second set of samples 230 which is labeled by a second fluorescent tag. First, the biochip detection system 100 is configured to locate and detect the first set of samples 220. For proper configuration to detect and locate the first set of samples 220, the source light filter 160 preferably substantially only allows light waves with an excitation wavelength corresponding to the first fluorescent tag to reach the biochip 210. Further, the sensor filter 130 preferably substantially only allows light waves with an emission wavelength corresponding to the first fluorescent tag to reach the CCD sensor 140.
  • After the biochip detection system [0031] 100 is finished detecting and locating the first set of samples 220, the system 100 is configured to detect and locate the second set of samples 230. For proper configuration to detect and locate the second set of samples 230, the source light filter 160′ preferably substantially only allows light waves with an excitation wavelength corresponding to the second fluorescent tag to reach the biochip 210. Further, the sensor filter 130′ preferably substantially only allows light waves with an emission wavelength corresponding to the second fluorescent tag to reach the CCD sensor 140. The filter can be manually changed. For systems used to routinely tests samples labeled with several known fluorescent tags, the filters can be automatically interchanged, for example, using a so-called “jukebox”. Although the first set of samples 220 and the second set of samples 230 are described as being labeled with a fluorescent tag, it will be apparent to those skilled in the art to substitute a fluorescent tag with a chemiluminescent tag, colormetric tag, and the like.
  • FIG. 3 illustrates the biochip detection system [0032] 100 configured to analyze a biochip 700 having a plurality of samples 710 wherein each of the plurality of samples 710 are preferably labeled by multiple fluorescent tags. The configuration of the biochip detection system 100 which includes the light source 150, the lens 120, the sensor filters 130 and 130′, the light source filters 160 and 160′, and the CCD sensor 140 remain identical to the biochip detection system 100 in FIG. 2. The sensor filters 130 and 130′ are used interchangeably, one each for detecting the presence of different fluorescent tags. The light source filters 160 and 160′ are used interchangeably to illuminate the biochip 700 with different wavelengths of light. It will be apparent to those skilled in the art that additional filters can be utilized. The plurality of samples 710 are represented as being labeled by a first fluorescent tag 720 and a second fluorescent tag 730. It will be apparent to those with ordinary skill in the art to label the plurality of samples 710 with any number of tags.
  • First, the biochip detection system [0033] 100 is configured to locate and detect the plurality of samples 710 that are labeled with the first fluorescent tag 720. For proper configuration to detect and locate the plurality of samples 710 that are labeled with the first fluorescent tag 720, the source light filter 160 preferably substantially only allows light waves with an excitation wavelength corresponding to the first fluorescent tag to reach the biochip 700. Further, the sensor filter 130 preferably substantially only allows light waves with an emission wavelength corresponding to the first fluorescent tag 720 to reach the CCD sensor 140.
  • After the biochip detection system [0034] 100 is finished detecting and locating the plurality of samples 710 that are labeled with the first fluorescent tag 720, the system 100 is configured to detect and locate the plurality of samples 710 that are labeled with the second fluorescent tag 730. For proper configuration to detect and locate the plurality of samples 710 that are labeled with the second fluorescent tag 730, the source light filter 160′ preferably substantially only allows light waves with an excitation wavelength corresponding to the second fluorescent tag 730 to reach the biochip 700. Further, the sensor filter 130′ preferably substantially only allows light waves with an emission wavelength corresponding to the second fluorescent tag 730 to reach the CCD sensor 140. The filter can be manually changed. For systems used to routinely tests samples labeled with several known fluorescent tags, the filters can be automatically interchanged, for example, using a so-called “jukebox”. Although the plurality of samples 710 are described as being labeled with multiple fluorescent tags, it will be apparent to those skilled in the art to substitute multiple fluorescent tags with multiple chemiluminescent tags, colormetric tags, and the like.
  • FIG. 4 illustrates a graph representing intensity of light along the vertical axis and wavelength along the horizontal axis. A curve [0035] 300 is representative of the light output from the light source 150 (FIGS. 1, 2, and 3). As observed from the curve 300, the light source 150 outputs light waves preferably at an uniform intensity over a range of wavelengths. A curve 310 is centered around λExcited and represents a desired light intensity and wavelength to strike a sample labeled with a particular fluorescent tag in order to excite this sample. A curve 320 is centered around λEmitted and represents an emitted light intensity and wavelength from this sample while this sample is excited by light waves represented by the curve 310.
  • The curves [0036] 300, 310, and 320 illustrate the functions of the light source filter 160 and the sensor filter 130 as illustrated in FIGS. 1, 2, and 3 and as described above. For example, while in operation, the light source 150 preferably outputs light waves represented by the curve 300. Preferably, the light source filter 160 substantially only allows light waves that have wavelengths centered around the λExcited to reach the sample labeled by this particular fluorescent tag. Consequently, these light waves that have wavelengths centered around the λExcited excite the sample and are represented by the curve 310. While excited, this sample preferably emits light waves that have wavelengths centered around the λEmitted. Preferably, the sensor filter 130 substantially only allows light waves that have wavelengths centered around the λEmitted (which are represented by the curve 320) to reach the CCD sensor 140.
  • By having the source light filter [0037] 160 prevent light waves that have wavelengths centered around the λEmitted from striking this sample, the source light filter 160 prevents erroneous light waves from passing through the sensor filter 130 and striking the CCD sensor 140. Further, by having the sensor filter 130 prevent light waves that have wavelengths centered around the λExcited from passing through the biochip 170 and then striking the CCD sensor 140, the sensor filter 130 prevents erroneous readings from the CCD sensor 140. As a result of the source light filter 160 and the sensor filter 130, fewer or no stray, erroneous light waves strike the CCD sensor 140.
  • FIG. 5 illustrates an external top view of an alternate embodiment of the biochip detection system [0038] 100. A main housing 400 is configured to hold the biochip 170 and the light source 150. The main housing 400 is also configured to be light proof. By being light proof, the main housing 400 prevents extraneous light waves from giving the CCD sensor 140 erroneous signals. At least one articulating mirror 410 is utilized within the main housing 400 for appropriately directing light waves from the light source 150 to the biochip 170. A camera housing 420 is utilized to hold the CCD sensor 140 and coupled to the main housing 400.
  • FIG. 6 illustrates an external side view of the alternate embodiment of the biochip detection system [0039] 100. The main housing 400 includes a drawer 440 which allows a user to change the biochip 170, adjust the light source filter 160, and/or adjust the light source 150. The drawer 440 includes appropriate seals to engage the main housing 400 such that the main housing 400 remains light proof. A filter box 480 is coupled to the main housing 400. The filter box 480 is configured to securely hold the sensor filter 130 and has an opening 450 to accept the sensor filter 130. The camera housing 420 is mounted to the filter box 480 via a camera mounting bracket 430. Preferably, a light shield 510 is mounted between the camera housing 420 and the filter box 480 to prevent stray light waves from entering either the camera housing 420, the main housing 400, or the filter box 480.
  • FIG. 7 illustrates an external perspective view of the alternate embodiment of the biochip detection system [0040] 100. For the sake of clarity, the camera housing 420, the camera mounting bracket 430, and the light shield 510 are omitted from FIG. 6. A fiber optic port 490 is provided in the main housing 400. The fiber optic port 490 allows the biochip detection system 100 to interface with an external light source which is capable of transmitting light via a fiber optic cable connected to the external light and the fiber optic port 490. The filter box 480 has a light channel 530 for allowing light to pass through the filter box 480 from the main housing 400 to the camera housing 420. Further, the filter box 480 also has an opening 505 to accept a ball plunger 500. A filter holder 460 is configured to hold at least one sensor filter 130 and has a plurality of notches 520. The filter holder 460 is configured to slide through the opening 450 in the filter box 480. The ball plunger 500 is configured to engage one of the plurality of notches 520 to appropriately position the filter holder 460 relative to the filter box 480.
  • A preferred embodiment of the external housing is similar to the alternate embodiment as shown in FIGS. 5, 6, and [0041] 7. A main difference between the alternate embodiment and the preferred embodiment is that the preferred embodiment does not utilize the filter box 480 and the filter holder 460 as shown in FIGS. 5, 6, and 7. Instead, the preferred embodiment of the external housing preferably couples the camera mount bracket 430 directly to the main housing 400. Further, the camera housing 420 as shown in FIGS. 5 and 6 is modified and replaced in the preferred embodiment by a camera housing 600. The camera housing 600 is illustrated in FIG. 8. Unlike the alternate embodiment of the camera housing 420 (FIGS. 5 and 6), the camera housing 600 preferably contains a filter wheel 610 which holds at least one sensor filter 130. Preferably, the filter wheel 610 optically couples the sensor filter 130 between the lens 120 and the CCD sensor 140. Further, the filter wheel 610 is preferably configured to change positions thus allowing different sensor filters 130 to be optically coupled between the lens 120 and the CCD sensor 140.
  • The present invention has been described in terms of specific embodiments incorporating details to facilitate the understanding of the principles of construction and operation of the invention. Such reference herein to specific embodiments and details thereof is not intended to limit the scope of the claims appended hereto. It will be apparent to those skilled in the art that modifications can be made in the embodiments chosen for illustration without departing from the spirit and scope of the invention. [0042]
  • Specifically, it will be apparent to one of ordinary skill in the art that the device of the present invention could be implemented in several different ways and the apparatus disclosed above is only illustrative of the preferred embodiment of the invention and is in no way a limitation. For example, it would be within the scope of the invention to vary the dimensions disclosed herein. In addition, it will be apparent that the various aspects of the above-described invention can be utilized singly or in combination with one or more of the other aspects of the invention described herein. In addition, the various elements of the present invention could be substituted with other elements. [0043]

Claims (19)

    What is claimed is:
  1. 1. An apparatus configured for analyzing a sample, the apparatus comprising:
    a. a sensor configured for detecting emitted light from the sample;
    b. a light source optically coupled to the sensor configured to illuminate the sample with an excitation light having a first wavelength; and
    c. a matched filter optically coupled between the sample and the sensor for allowing substantially only the emitted light having a second wavelength to pass therethrough and strike the sensor.
  2. 2. The apparatus according to
    claim 1
    wherein the sensor is a charge coupled device.
  3. 3. The apparatus according to
    claim 1
    wherein the sensor is a two dimensional charge coupled device.
  4. 4. The apparatus according to
    claim 1
    wherein the light source is a coherent light source such as a laser.
  5. 5. The apparatus according to
    claim 1
    wherein the light source is a broad spectrum light source and the apparatus further comprising a secondary filter located between the broad spectrum light source and the sample such that substantially only the excitation light with the first wavelength reaches the sample.
  6. 6. The apparatus according to
    claim 1
    further comprising a lens optically coupled between the sample and the sensor for focussing the emitted light.
  7. 7. An apparatus configured for analyzing a biochip containing a tag labeled sample, the apparatus comprising
    a. a two dimensional CCD sensor for detecting emitted light from the tag labeled sample on the biochip; and
    b. a lens optically coupled between the two dimensional CCD sensor and the biochip and configured to transmit the emitted light to the two dimensional CCD sensor wherein the lens is configured to be within two inches of the tag labeled sample.
  8. 8. The apparatus according to
    claim 7
    further comprising a light source to illuminate the tag labeled sample.
  9. 9. The apparatus according to
    claim 8
    wherein the light source is a broad spectrum light source.
  10. 10. The apparatus according to
    claim 8
    further comprising a light source filter configured to be optically coupled between the light source and the tag labeled sample wherein the light source filter is configured to only substantially allow light waves having an excitation wavelength corresponding to the tag labeled sample to reach the tag labeled sample.
  11. 11. The apparatus according to
    claim 7
    further comprising a sensor filter optically coupled between the two dimensional CCD sensor and the lens wherein the sensor filter is configured to only substantially allow light waves emitted from the tag labeled sample to reach the CCD sensor.
  12. 12. A system configured to detect and locate fluorescently labeled samples on a biochip, the biochip having a plurality of samples, the system comprising:
    a. a light source configured to simultaneously illuminate all the fluorescently labeled samples;
    b. a two dimensional CCD sensor optically coupled to the light source and configured for concurrently detecting and locating emitted light from the fluorescently labeled samples on the biochip; and
    c. a lens optically coupled between the light source and the two dimensional CCD sensor and configured to appropriately magnify the biochip onto the two dimensional CCD sensor.
  13. 13. A system configured to detect and locate a first set of samples labeled by a first fluorescent tag and a second set of samples labeled by a second fluorescent tag, the system comprising:
    a. a light source configured to simultaneously illuminate all the flourescently labeled samples;
    b. a two dimensional CCD sensor optically coupled to the light source and configured for concurrently detecting and locating a first emitted light from the first set of samples and a second emitted light from the second set of samples;
    c. a lens optically coupled between the light source and the two dimensional CCD sensor and configured to transmit the first emitted light and the second emitted light to the two dimensional CCD sensor;
    d. a first light source filter selectively and optically coupled to the light source and configured for substantially only transmitting a first illuminating light to the first set of samples to excite the first set of samples;
    e. a first sensor filter selectively and optically coupled to the two dimensional CCD sensor and configured for substantially only transmitting the first emitted light to the two dimensional CCD sensor;
    f. a second light source filter selectively and optically coupled to the light source and configured for substantially only transmitting a second illuminating light to the second set of samples to excite the second set of samples; and
    g. a second sensor filter selectively and optically coupled to the two dimensional CCD sensor and configured for substantially only transmitting the second emitted light to the two dimensional CCD sensor.
  14. 14. A method of detecting and locating a first sample labeled by a first fluorescent tag and a second sample labeled by a second fluorescent tag wherein the first sample and the second sample are on a biochip, the method comprising the following steps:
    a. selectively exciting the first sample by substantially directing only light having a first excitation wavelength for exciting the first fluorescent tag from a broad spectrum light source to the first sample;
    b. selectively detecting the first sample during the step of exciting the first sample by substantially directing only light having a first emission wavelength emitted by and from the first sample to a two dimensional CCD sensor;
    c. selectively exciting the second sample by substantially directing only light having a second excitation wavelength for exciting the second fluorescent tag from the broad spectrum light source to the second sample; and
    d. selectively detecting the second sample during the step of exciting the second sample by substantially directing only light having a second emission wavelength emitted by and from the second sample to the two dimensional CCD sensor.
  15. 15. A method of detecting and locating a sample labeled with a fluorescent tag, the method comprising the following steps:
    a. illuminating the sample with a light source;
    b. focussing an emitted light from the sample via a lens wherein the lens is located at a distance that is less than 6.0 inches from the sample; and
    c. detecting the emitted light from the sample via a CCD sensor.
  16. 16. The method according to
    claim 15
    further comprising inserting a light source filter adjacent to the light source wherein the light source filter is configured to substantially block light waves that have wavelengths outside an excitation wavelength range of the fluorescent tag from reaching the sample.
  17. 17. The method according to
    claim 15
    further comprising inserting a sensor filter adjacent to the CCD sensor wherein the sensor filter is configured to substantially block light waves that have wavelengths outside an emission wavelength range of the fluorescent tag from reaching the CCD sensor.
  18. 18. The method according to
    claim 15
    wherein the CCD sensor comprises a two dimensional array of charge coupled devices.
  19. 19. The method according to
    claim 15
    wherein the light source is a broad spectrum light source.
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Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040092001A1 (en) * 2001-03-01 2004-05-13 3M Innovative Properties Company Automated imaging and harvesting of colonies on thin film culture devices
US20040101952A1 (en) * 2002-11-27 2004-05-27 3M Innovative Properties Company Loading and ejection systems for biological growth plate scanner
US20040101189A1 (en) * 2002-11-27 2004-05-27 3M Innovative Properties Company Biological growth plate scanner with automated image processing profile selection
US20040102903A1 (en) * 2002-11-27 2004-05-27 Graessle Josef A. Biological growth plate scanner
US20040101951A1 (en) * 2002-11-27 2004-05-27 Albert Vent Mounting platform for biological growth plate scanner
US20040101954A1 (en) * 2002-11-27 2004-05-27 Graessle Josef A. Back side plate illumination for biological growth plate scanner
US20050027178A1 (en) * 2003-07-29 2005-02-03 Iddan Gavriel J. In vivo device and method for collecting oximetry data
WO2004051283A3 (en) * 2002-11-27 2005-02-17 3M Innovative Properties Co Biological growth plate scanner
US20050043617A1 (en) * 2002-11-29 2005-02-24 Mordechai Frisch Methods, device and system for in vivo detection
US20050053265A1 (en) * 2003-09-04 2005-03-10 3M Innovative Properties Company Biological growth plate scanner with automated intake
US20050053266A1 (en) * 2003-09-05 2005-03-10 Plumb Michael R. Counting biological agents on biological growth plates
US20060106316A1 (en) * 2002-08-13 2006-05-18 Yoram Palti System for in vivo sampling and analysis
US7468044B2 (en) 2001-01-16 2008-12-23 Given Imaging Ltd. Device, system and method for determining in vivo body lumen conditions
US20110153220A1 (en) * 2008-03-04 2011-06-23 Bolea Phillip A Processing of biological growth media based on measured manufacturing characteristics
US20110158499A1 (en) * 2008-03-04 2011-06-30 Bolea Phillip A Information management in automated processing of biological growth media
US20120002031A1 (en) * 2008-12-02 2012-01-05 The Regents Of The University Of California Imaging Arrangement and Microscope
US8515507B2 (en) 2008-06-16 2013-08-20 Given Imaging Ltd. Device and method for detecting in-vivo pathology
CN105548179A (en) * 2015-12-04 2016-05-04 深圳市赛尔生物技术有限公司 Method and system for determination of biochip based on transmitted light or self luminescence

Families Citing this family (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6271042B1 (en) * 1998-08-26 2001-08-07 Alpha Innotech Corporation Biochip detection system
US6136541A (en) 1999-02-22 2000-10-24 Vialogy Corporation Method and apparatus for analyzing hybridized biochip patterns using resonance interactions employing quantum expressor functions
US6142681A (en) 1999-02-22 2000-11-07 Vialogy Corporation Method and apparatus for interpreting hybridized bioelectronic DNA microarray patterns using self-scaling convergent reverberant dynamics
WO2000079326A1 (en) 1999-06-18 2000-12-28 Genomic Solutions Inc. An automated, ccd-based microarray imaging system
US6362006B1 (en) * 2000-03-13 2002-03-26 General Electric Company Rapid parallel determination of non-volatile analytes in complex combinatorial samples
GB0027293D0 (en) * 2000-11-08 2000-12-27 Proimmune Ltd Analysis of biolocical an biochemical assays
US6403970B1 (en) * 2000-12-05 2002-06-11 Industrial Technology Research Institute Matrix biochip sensing system
US6949377B2 (en) * 2001-03-05 2005-09-27 Ho Winston Z Chemiluminescence-based microfluidic biochip
CN101545012A (en) * 2001-05-11 2009-09-30 松下电器产业株式会社 Biomolecular substrate and method and apparatus for examination and diagnosis using the same
WO2003014400A1 (en) * 2001-08-08 2003-02-20 Applied Precision, Llc Time-delay integration imaging of biological specimens
KR20030037314A (en) * 2001-11-01 2003-05-14 (주)다이아칩 Apparatus for analyzing fluorescence image of biochip
DE10321490B3 (en) * 2002-02-05 2004-10-14 Infineon Technologies Ag Electrochemical sensor, as a biochip working on a redox cycling principle, has one circuit is a potentiostat coupled to the sensor electrode and a second circuit has a condenser for potential comparison
DE10204652B4 (en) * 2002-02-05 2004-07-22 Infineon Technologies Ag Circuit arrangement, electrochemical sensor, the sensor arrangement and method for processing a current signal provided via a sensor electrode
US6620623B1 (en) * 2002-05-06 2003-09-16 The University Of Chicago Biochip reader with enhanced illumination and bioarray positioning apparatus
US7122153B2 (en) * 2003-01-08 2006-10-17 Ho Winston Z Self-contained microfluidic biochip and apparatus
US6970240B2 (en) * 2003-03-10 2005-11-29 Applera Corporation Combination reader
DE10315074A1 (en) 2003-04-02 2004-10-14 Clondiag Chip Technologies Gmbh Apparatus for reproduction and for detecting nucleic acids
US6995901B2 (en) * 2004-01-15 2006-02-07 Alpha Innotech Corporation Optical analysis systems
US20050157299A1 (en) * 2004-01-15 2005-07-21 Heffelfinger David M. Optical analysis systems
US6853454B1 (en) 2004-01-15 2005-02-08 Alpha Innotech Corporation Optical analysis systems
DE102004022263A1 (en) 2004-05-06 2005-12-15 Clondiag Chip Technologies Gmbh Device and method for the detection of molecular interactions
CN1312476C (en) * 2004-08-27 2007-04-25 清华大学 Method and system for detecting biological chip by space phase modulation interference array
EP1792263A2 (en) 2004-09-02 2007-06-06 Vialogy Corporation Detecting events of interest using quantum resonance interferometry
WO2006031537A3 (en) * 2004-09-09 2006-08-17 Alpha Innotech Corp Microplate analysis system and method
US20060186346A1 (en) * 2005-02-18 2006-08-24 Academia Sinica Method and system for reading microarrays
WO2007041734A3 (en) 2005-10-07 2007-06-21 Anagnostics Bioanalysis Gmbh Device for the analysis of liquid samples
DE102005052713A1 (en) 2005-11-04 2007-05-16 Clondiag Chip Tech Gmbh Device and method for the detection of molecular interactions
US7463353B2 (en) * 2006-05-31 2008-12-09 Uchicago Argonne, Llc Modular, micro-scale, optical array and biodetection system
WO2008046930A1 (en) 2006-10-20 2008-04-24 Clondiag Gmbh Assay devices and methods for the detection of analytes
DE102007031526B4 (en) 2007-07-06 2010-07-08 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Use of an anode in a fuel cell for oxidation of ethanol and / or at least one C3 to C10-containing alcohol
US8237923B2 (en) * 2010-04-15 2012-08-07 Yayatech Co., Ltd. Bio-sample image pickup device

Citations (55)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4415732A (en) * 1981-03-27 1983-11-15 University Patents, Inc. Phosphoramidite compounds and processes
US4458066A (en) * 1980-02-29 1984-07-03 University Patents, Inc. Process for preparing polynucleotides
US4537861A (en) * 1983-02-03 1985-08-27 Elings Virgil B Apparatus and method for homogeneous immunoassay
US4816513A (en) * 1984-03-23 1989-03-28 Applied Biosystems, Inc. Automated polypeptide synthesis process
US4922092A (en) * 1986-11-26 1990-05-01 Image Research Limited High sensitivity optical imaging apparatus
US5047524A (en) * 1988-12-21 1991-09-10 Applied Biosystems, Inc. Automated system for polynucleotide synthesis and purification
US5053454A (en) * 1989-02-15 1991-10-01 Sri International Multiple polymer synthesizer
US5091652A (en) * 1990-01-12 1992-02-25 The Regents Of The University Of California Laser excited confocal microscope fluorescence scanner and method
US5093268A (en) * 1988-04-28 1992-03-03 Igen, Inc. Apparatus for conducting a plurality of simultaneous measurements of electrochemiluminescent phenomena
US5096807A (en) * 1985-03-06 1992-03-17 Murex Corporation Imaging immunoassay detection system with background compensation and its use
US5112736A (en) * 1989-06-14 1992-05-12 University Of Utah Dna sequencing using fluorescence background electroblotting membrane
US5132418A (en) * 1980-02-29 1992-07-21 University Patents, Inc. Process for preparing polynucleotides
US5192980A (en) * 1990-06-27 1993-03-09 A. E. Dixon Apparatus and method for method for spatially- and spectrally-resolved measurements
US5239484A (en) * 1988-03-31 1993-08-24 Takeda Chemical Industries, Ltd. Automatic synthesis apparatus
US5262530A (en) * 1988-12-21 1993-11-16 Applied Biosystems, Inc. Automated system for polynucleotide synthesis and purification
US5297288A (en) * 1989-11-28 1994-03-22 United States Biochemical Corporation System for use with a high resolution scanner for scheduling a sequence of software tools for determining the presence of bands in DNA sequencing samples
US5324633A (en) * 1991-11-22 1994-06-28 Affymax Technologies N.V. Method and apparatus for measuring binding affinity
US5324483A (en) * 1992-10-08 1994-06-28 Warner-Lambert Company Apparatus for multiple simultaneous synthesis
US5356776A (en) * 1991-09-10 1994-10-18 Hitachi, Ltd. DNA measuring method
US5395594A (en) * 1991-08-26 1995-03-07 Shimadzu Corporation Simultaneous multiple chemical synthesizer
US5427930A (en) * 1990-01-26 1995-06-27 Abbott Laboratories Amplification of target nucleic acids using gap filling ligase chain reaction
US5453247A (en) * 1990-04-04 1995-09-26 The Rockefeller University Instrument and method for the sequencing of genome
US5468606A (en) * 1989-09-18 1995-11-21 Biostar, Inc. Devices for detection of an analyte based upon light interference
US5472672A (en) * 1993-10-22 1995-12-05 The Board Of Trustees Of The Leland Stanford Junior University Apparatus and method for polymer synthesis using arrays
US5510270A (en) * 1989-06-07 1996-04-23 Affymax Technologies N.V. Synthesis and screening of immobilized oligonucleotide arrays
US5512490A (en) * 1994-08-11 1996-04-30 Trustees Of Tufts College Optical sensor, optical sensing apparatus, and methods for detecting an analyte of interest using spectral recognition patterns
US5522272A (en) * 1993-11-04 1996-06-04 Bellaire Industries, Inc. Gas emission sample container with heating means
US5541113A (en) * 1993-09-22 1996-07-30 Beckman Instruments, Inc. Method for detecting an analyte using an electrochemical luminescent transition metal label
US5545531A (en) * 1995-06-07 1996-08-13 Affymax Technologies N.V. Methods for making a device for concurrently processing multiple biological chip assays
US5547839A (en) * 1989-06-07 1996-08-20 Affymax Technologies N.V. Sequencing of surface immobilized polymers utilizing microflourescence detection
US5563033A (en) * 1985-10-22 1996-10-08 The University Of Massachusetts Medical Center Detection of individual gene transcription
US5571639A (en) * 1994-05-24 1996-11-05 Affymax Technologies N.V. Computer-aided engineering system for design of sequence arrays and lithographic masks
US5578832A (en) * 1994-09-02 1996-11-26 Affymetrix, Inc. Method and apparatus for imaging a sample on a device
US5585639A (en) * 1995-07-27 1996-12-17 Hewlett-Packard Company Optical scanning apparatus
US5597694A (en) * 1993-10-07 1997-01-28 Massachusetts Institute Of Technology Interspersed repetitive element-bubble amplification of nucleic acids
US5605662A (en) * 1993-11-01 1997-02-25 Nanogen, Inc. Active programmable electronic devices for molecular biological analysis and diagnostics
US5631734A (en) * 1994-02-10 1997-05-20 Affymetrix, Inc. Method and apparatus for detection of fluorescently labeled materials
US5633365A (en) * 1993-10-06 1997-05-27 The Regents Of The University Of California Detection of amplified or deleted chromosomal regions
US5632957A (en) * 1993-11-01 1997-05-27 Nanogen Molecular biological diagnostic systems including electrodes
US5635402A (en) * 1992-03-05 1997-06-03 Alfano; Robert R. Technique for determining whether a cell is malignant as opposed to non-malignant using extrinsic fluorescence spectroscopy
US5639428A (en) * 1994-07-19 1997-06-17 Becton Dickinson And Company Method and apparatus for fully automated nucleic acid amplification, nucleic acid assay and immunoassay
US5645801A (en) * 1993-10-21 1997-07-08 Abbott Laboratories Device and method for amplifying and detecting target nucleic acids
US5645114A (en) * 1992-05-11 1997-07-08 Cytologix Corporation Dispensing assembly with interchangeable cartridge pumps
US5653939A (en) * 1991-11-19 1997-08-05 Massachusetts Institute Of Technology Optical and electrical methods and apparatus for molecule detection
US5690894A (en) * 1995-05-23 1997-11-25 The Regents Of The University Of California High density array fabrication and readout method for a fiber optic biosensor
US5707797A (en) * 1993-01-08 1998-01-13 Ctrc Research Foundation Color imaging method for mapping stretched DNA hybridized with fluorescently labeled oligonucleotide probes
US5720928A (en) * 1988-09-15 1998-02-24 New York University Image processing and analysis of individual nucleic acid molecules
US5720923A (en) * 1993-07-28 1998-02-24 The Perkin-Elmer Corporation Nucleic acid amplification reaction apparatus
US5736257A (en) * 1995-04-25 1998-04-07 Us Navy Photoactivatable polymers for producing patterned biomolecular assemblies
US5736333A (en) * 1996-06-04 1998-04-07 The Perkin-Elmer Corporation Passive internal references for the detection of nucleic acid amplification products
US5744305A (en) * 1989-06-07 1998-04-28 Affymetrix, Inc. Arrays of materials attached to a substrate
US5764409A (en) * 1996-04-26 1998-06-09 Alpha Innotech Corp Elimination of vibration by vibration coupling in microscopy applications
US5964781A (en) * 1995-05-19 1999-10-12 General Surgical Innovations, Inc. Skin seal with inflatable membrane
US6087102A (en) * 1998-01-07 2000-07-11 Clontech Laboratories, Inc. Polymeric arrays and methods for their use in binding assays
US6271042B1 (en) * 1998-08-26 2001-08-07 Alpha Innotech Corporation Biochip detection system

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2129787A1 (en) * 1993-08-27 1995-02-28 Russell G. Higuchi Monitoring multiple amplification reactions simultaneously and analyzing same
US5849486A (en) 1993-11-01 1998-12-15 Nanogen, Inc. Methods for hybridization analysis utilizing electrically controlled hybridization
WO1996027025A1 (en) 1995-02-27 1996-09-06 Ely Michael Rabani Device, compounds, algorithms, and methods of molecular characterization and manipulation with molecular parallelism
CA2257287A1 (en) 1996-05-30 1997-12-04 D. Lansing Taylor Miniaturized cell array methods and apparatus for cell-based screening
WO1999000520A1 (en) 1997-06-30 1999-01-07 The Government Of The United States Of America, Reresented By The Secretary Of The Department Of Health And Human Services Spectral cloning-a new technical approach to the cloning and characterization of every chromosomal aberration in cancer samples
US6197503B1 (en) 1997-11-26 2001-03-06 Ut-Battelle, Llc Integrated circuit biochip microsystem containing lens

Patent Citations (58)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5132418A (en) * 1980-02-29 1992-07-21 University Patents, Inc. Process for preparing polynucleotides
US4458066A (en) * 1980-02-29 1984-07-03 University Patents, Inc. Process for preparing polynucleotides
US4415732A (en) * 1981-03-27 1983-11-15 University Patents, Inc. Phosphoramidite compounds and processes
US4537861A (en) * 1983-02-03 1985-08-27 Elings Virgil B Apparatus and method for homogeneous immunoassay
US4816513A (en) * 1984-03-23 1989-03-28 Applied Biosystems, Inc. Automated polypeptide synthesis process
US5096807A (en) * 1985-03-06 1992-03-17 Murex Corporation Imaging immunoassay detection system with background compensation and its use
US5563033A (en) * 1985-10-22 1996-10-08 The University Of Massachusetts Medical Center Detection of individual gene transcription
US4922092A (en) * 1986-11-26 1990-05-01 Image Research Limited High sensitivity optical imaging apparatus
US5239484A (en) * 1988-03-31 1993-08-24 Takeda Chemical Industries, Ltd. Automatic synthesis apparatus
US5093268A (en) * 1988-04-28 1992-03-03 Igen, Inc. Apparatus for conducting a plurality of simultaneous measurements of electrochemiluminescent phenomena
US5720928A (en) * 1988-09-15 1998-02-24 New York University Image processing and analysis of individual nucleic acid molecules
US5262530A (en) * 1988-12-21 1993-11-16 Applied Biosystems, Inc. Automated system for polynucleotide synthesis and purification
US5047524A (en) * 1988-12-21 1991-09-10 Applied Biosystems, Inc. Automated system for polynucleotide synthesis and purification
US5053454A (en) * 1989-02-15 1991-10-01 Sri International Multiple polymer synthesizer
US5510270A (en) * 1989-06-07 1996-04-23 Affymax Technologies N.V. Synthesis and screening of immobilized oligonucleotide arrays
US5547839A (en) * 1989-06-07 1996-08-20 Affymax Technologies N.V. Sequencing of surface immobilized polymers utilizing microflourescence detection
US5744305A (en) * 1989-06-07 1998-04-28 Affymetrix, Inc. Arrays of materials attached to a substrate
US5112736A (en) * 1989-06-14 1992-05-12 University Of Utah Dna sequencing using fluorescence background electroblotting membrane
US5468606A (en) * 1989-09-18 1995-11-21 Biostar, Inc. Devices for detection of an analyte based upon light interference
US5297288A (en) * 1989-11-28 1994-03-22 United States Biochemical Corporation System for use with a high resolution scanner for scheduling a sequence of software tools for determining the presence of bands in DNA sequencing samples
US5091652A (en) * 1990-01-12 1992-02-25 The Regents Of The University Of California Laser excited confocal microscope fluorescence scanner and method
US5427930A (en) * 1990-01-26 1995-06-27 Abbott Laboratories Amplification of target nucleic acids using gap filling ligase chain reaction
US5453247A (en) * 1990-04-04 1995-09-26 The Rockefeller University Instrument and method for the sequencing of genome
US5192980A (en) * 1990-06-27 1993-03-09 A. E. Dixon Apparatus and method for method for spatially- and spectrally-resolved measurements
US5395594A (en) * 1991-08-26 1995-03-07 Shimadzu Corporation Simultaneous multiple chemical synthesizer
US5356776A (en) * 1991-09-10 1994-10-18 Hitachi, Ltd. DNA measuring method
US5653939A (en) * 1991-11-19 1997-08-05 Massachusetts Institute Of Technology Optical and electrical methods and apparatus for molecule detection
US5324633A (en) * 1991-11-22 1994-06-28 Affymax Technologies N.V. Method and apparatus for measuring binding affinity
US5635402A (en) * 1992-03-05 1997-06-03 Alfano; Robert R. Technique for determining whether a cell is malignant as opposed to non-malignant using extrinsic fluorescence spectroscopy
US5645114A (en) * 1992-05-11 1997-07-08 Cytologix Corporation Dispensing assembly with interchangeable cartridge pumps
US5324483B1 (en) * 1992-10-08 1996-09-24 Warner Lambert Co Apparatus for multiple simultaneous synthesis
US5324483A (en) * 1992-10-08 1994-06-28 Warner-Lambert Company Apparatus for multiple simultaneous synthesis
US5707797A (en) * 1993-01-08 1998-01-13 Ctrc Research Foundation Color imaging method for mapping stretched DNA hybridized with fluorescently labeled oligonucleotide probes
US5720923A (en) * 1993-07-28 1998-02-24 The Perkin-Elmer Corporation Nucleic acid amplification reaction apparatus
US5541113A (en) * 1993-09-22 1996-07-30 Beckman Instruments, Inc. Method for detecting an analyte using an electrochemical luminescent transition metal label
US5633365A (en) * 1993-10-06 1997-05-27 The Regents Of The University Of California Detection of amplified or deleted chromosomal regions
US5597694A (en) * 1993-10-07 1997-01-28 Massachusetts Institute Of Technology Interspersed repetitive element-bubble amplification of nucleic acids
US5645801A (en) * 1993-10-21 1997-07-08 Abbott Laboratories Device and method for amplifying and detecting target nucleic acids
US5529756A (en) * 1993-10-22 1996-06-25 The Board Of Trustees Of The Leland Stanford Junior University Apparatus and method for polymer synthesis using arrays
US5472672A (en) * 1993-10-22 1995-12-05 The Board Of Trustees Of The Leland Stanford Junior University Apparatus and method for polymer synthesis using arrays
US5632957A (en) * 1993-11-01 1997-05-27 Nanogen Molecular biological diagnostic systems including electrodes
US5605662A (en) * 1993-11-01 1997-02-25 Nanogen, Inc. Active programmable electronic devices for molecular biological analysis and diagnostics
US5522272A (en) * 1993-11-04 1996-06-04 Bellaire Industries, Inc. Gas emission sample container with heating means
US5631734A (en) * 1994-02-10 1997-05-20 Affymetrix, Inc. Method and apparatus for detection of fluorescently labeled materials
US5571639A (en) * 1994-05-24 1996-11-05 Affymax Technologies N.V. Computer-aided engineering system for design of sequence arrays and lithographic masks
US5593839A (en) * 1994-05-24 1997-01-14 Affymetrix, Inc. Computer-aided engineering system for design of sequence arrays and lithographic masks
US5639428A (en) * 1994-07-19 1997-06-17 Becton Dickinson And Company Method and apparatus for fully automated nucleic acid amplification, nucleic acid assay and immunoassay
US5512490A (en) * 1994-08-11 1996-04-30 Trustees Of Tufts College Optical sensor, optical sensing apparatus, and methods for detecting an analyte of interest using spectral recognition patterns
US5578832A (en) * 1994-09-02 1996-11-26 Affymetrix, Inc. Method and apparatus for imaging a sample on a device
US5736257A (en) * 1995-04-25 1998-04-07 Us Navy Photoactivatable polymers for producing patterned biomolecular assemblies
US5964781A (en) * 1995-05-19 1999-10-12 General Surgical Innovations, Inc. Skin seal with inflatable membrane
US5690894A (en) * 1995-05-23 1997-11-25 The Regents Of The University Of California High density array fabrication and readout method for a fiber optic biosensor
US5545531A (en) * 1995-06-07 1996-08-13 Affymax Technologies N.V. Methods for making a device for concurrently processing multiple biological chip assays
US5585639A (en) * 1995-07-27 1996-12-17 Hewlett-Packard Company Optical scanning apparatus
US5764409A (en) * 1996-04-26 1998-06-09 Alpha Innotech Corp Elimination of vibration by vibration coupling in microscopy applications
US5736333A (en) * 1996-06-04 1998-04-07 The Perkin-Elmer Corporation Passive internal references for the detection of nucleic acid amplification products
US6087102A (en) * 1998-01-07 2000-07-11 Clontech Laboratories, Inc. Polymeric arrays and methods for their use in binding assays
US6271042B1 (en) * 1998-08-26 2001-08-07 Alpha Innotech Corporation Biochip detection system

Cited By (45)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7901366B2 (en) 2001-01-16 2011-03-08 Given Imaging, Ltd. System and method for determining in vivo body lumen conditions
US7468044B2 (en) 2001-01-16 2008-12-23 Given Imaging Ltd. Device, system and method for determining in vivo body lumen conditions
US20090076370A1 (en) * 2001-01-16 2009-03-19 Iddan Gavriel J System and method for determining in vivo body lumen conditions
US20040092001A1 (en) * 2001-03-01 2004-05-13 3M Innovative Properties Company Automated imaging and harvesting of colonies on thin film culture devices
US7684840B2 (en) 2002-08-13 2010-03-23 Given Imaging, Ltd. System and method for in-vivo sampling and analysis
US20060106316A1 (en) * 2002-08-13 2006-05-18 Yoram Palti System for in vivo sampling and analysis
US7351574B2 (en) 2002-11-27 2008-04-01 3M Innovative Properties Company Loading and ejection systems for biological growth plate scanner
WO2004051283A3 (en) * 2002-11-27 2005-02-17 3M Innovative Properties Co Biological growth plate scanner
US8094916B2 (en) 2002-11-27 2012-01-10 3M Innovative Properties Company Biological growth plate scanner
US20110102582A1 (en) * 2002-11-27 2011-05-05 3M Innovative Properties Company Biological growth plate scanner
US8759080B2 (en) 2002-11-27 2014-06-24 3M Innovative Properties Company Back side plate illumination for biological growth plate scanner
US20040101951A1 (en) * 2002-11-27 2004-05-27 Albert Vent Mounting platform for biological growth plate scanner
US7901933B2 (en) 2002-11-27 2011-03-08 3M Innovative Properties Company Methods of processing a biological growth plate in a biological growth plate scanner
US7298885B2 (en) 2002-11-27 2007-11-20 3M Innovative Properties Company Biological growth plate scanner with automated image processing profile selection
US20100330610A1 (en) * 2002-11-27 2010-12-30 3M Innovative Properties Company Methods of processing a biological growth plate in a biological growth plate scanner
US7319031B2 (en) 2002-11-27 2008-01-15 3M Innovative Properties Company Mounting platform for biological growth plate scanner
US20080064089A1 (en) * 2002-11-27 2008-03-13 3M Innovative Properties Company Biological growth plate scanner with automated image processing profile selection
US20040102903A1 (en) * 2002-11-27 2004-05-27 Graessle Josef A. Biological growth plate scanner
US20080090286A1 (en) * 2002-11-27 2008-04-17 3M Innovative Properties Company Mounting platform for biological growth plate scanner
US20040101189A1 (en) * 2002-11-27 2004-05-27 3M Innovative Properties Company Biological growth plate scanner with automated image processing profile selection
US20040101952A1 (en) * 2002-11-27 2004-05-27 3M Innovative Properties Company Loading and ejection systems for biological growth plate scanner
US20090135603A1 (en) * 2002-11-27 2009-05-28 3M Innovative Properties Company Back side plate illumination for biological growth plate scanner
US20040101954A1 (en) * 2002-11-27 2004-05-27 Graessle Josef A. Back side plate illumination for biological growth plate scanner
US7787928B2 (en) 2002-11-29 2010-08-31 Given Imaging, Ltd. Methods, device and system for in vivo detection
US20050043617A1 (en) * 2002-11-29 2005-02-24 Mordechai Frisch Methods, device and system for in vivo detection
US7460896B2 (en) 2003-07-29 2008-12-02 Given Imaging Ltd. In vivo device and method for collecting oximetry data
US20050027178A1 (en) * 2003-07-29 2005-02-03 Iddan Gavriel J. In vivo device and method for collecting oximetry data
US20050053265A1 (en) * 2003-09-04 2005-03-10 3M Innovative Properties Company Biological growth plate scanner with automated intake
US7496225B2 (en) 2003-09-04 2009-02-24 3M Innovative Properties Company Biological growth plate scanner with automated intake
US7865008B2 (en) 2003-09-04 2011-01-04 3M Innovative Properties Company Biological growth plate scanner with automated intake
US8260026B2 (en) 2003-09-05 2012-09-04 3M Innovative Properties Company Counting biological agents on biological growth plates
US20050053266A1 (en) * 2003-09-05 2005-03-10 Plumb Michael R. Counting biological agents on biological growth plates
US7298886B2 (en) 2003-09-05 2007-11-20 3M Innovative Properties Company Counting biological agents on biological growth plates
US7957575B2 (en) 2003-09-05 2011-06-07 3M Innovative Properties Company Counting biological agents on biological growth plates
US20080003562A1 (en) * 2003-09-05 2008-01-03 3M Innovative Properties Company Counting biological agents on biological growth plates
US20100266192A1 (en) * 2003-09-05 2010-10-21 3M Innovative Properties Company Counting biological agents on biological growth plates
US7738689B2 (en) 2003-09-05 2010-06-15 3M Innovative Properties Company Counting biological agents on biological growth plates
US20110158499A1 (en) * 2008-03-04 2011-06-30 Bolea Phillip A Information management in automated processing of biological growth media
US8417013B2 (en) 2008-03-04 2013-04-09 3M Innovative Properties Company Information management in automated processing of biological growth media
US20110153220A1 (en) * 2008-03-04 2011-06-23 Bolea Phillip A Processing of biological growth media based on measured manufacturing characteristics
US9933446B2 (en) 2008-03-04 2018-04-03 3M Innovative Properties Company Processing of biological growth media based on measured manufacturing characteristics
US8515507B2 (en) 2008-06-16 2013-08-20 Given Imaging Ltd. Device and method for detecting in-vivo pathology
US20120002031A1 (en) * 2008-12-02 2012-01-05 The Regents Of The University Of California Imaging Arrangement and Microscope
US9213176B2 (en) * 2008-12-02 2015-12-15 The Regents Of The University Of California Imaging arrangement and microscope
CN105548179A (en) * 2015-12-04 2016-05-04 深圳市赛尔生物技术有限公司 Method and system for determination of biochip based on transmitted light or self luminescence

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