WO2009051416A1 - Portable optical device for multi-chamber fluorescence measurement and method for multi-chamber fluorescence measurement using the same - Google Patents

Portable optical device for multi-chamber fluorescence measurement and method for multi-chamber fluorescence measurement using the same Download PDF

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Publication number
WO2009051416A1
WO2009051416A1 PCT/KR2008/006108 KR2008006108W WO2009051416A1 WO 2009051416 A1 WO2009051416 A1 WO 2009051416A1 KR 2008006108 W KR2008006108 W KR 2008006108W WO 2009051416 A1 WO2009051416 A1 WO 2009051416A1
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WIPO (PCT)
Prior art keywords
fluorescence signal
processing unit
fluorescence
optical device
sample processing
Prior art date
Application number
PCT/KR2008/006108
Other languages
French (fr)
Inventor
Min-Su Lee
Young-Ki Lee
Gyeong-Sik Ok
Original Assignee
Seed Biochips Co., Ltd.
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Application filed by Seed Biochips Co., Ltd. filed Critical Seed Biochips Co., Ltd.
Publication of WO2009051416A1 publication Critical patent/WO2009051416A1/en

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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 sub-millimetre waves, infrared, visible or ultraviolet 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
    • 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 sub-millimetre waves, infrared, visible or ultraviolet 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
    • 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 sub-millimetre waves, infrared, visible or ultraviolet light
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip

Definitions

  • the present invention relates to a portable optical device for multi-chamber fluorescence measurement and a method for multi-chamber fluorescence measurement using the same. More particularly, the present invention relates to an optical device for multi-chamber fluorescence measurement in a point-of-care testing application, which is compact-sized, portable, and driven with low power consumption and fabricated cost-effectively, and a method for multi-chamber fluorescence measurement using the same.
  • Background Art is compact-sized, portable, and driven with low power consumption and fabricated cost-effectively, and a method for multi-chamber fluorescence measurement using the same.
  • a lab-on-a-chip is a device that integrates all necessary functionalities conducted in a lab on a bio-chip no larger than a fingernail. This realizes a system that can perform biological analysis fast and cheaply, which will otherwise take a long time and expensive cost, by making microchannels in size not exceeding micro- or nano- liter using materials such as plastics, glasses, or silicons.
  • the LOC has replaced e xperiments or tests that required extensive studies in the lab with an efficient and convenient test that deals with an extremely small amount of sample or feed.
  • This next-generation diagnostic chip device is capable of detecting cancers, or counting white blood cells or red blood cells based on just a single drop of blood.
  • the LOC is highly value-added, and the use of this technology has expanded variously, for example, in fields such as livestock farming or environment mainly thanks to the rapid advances in biotechnology.
  • the LOC is even capable of high speed parallel processing, when it is constructed as a multi-channel system.
  • a variety of mechanical, chemical, or electrical ways of measurements can be used to measure biological reaction on a LOC, but among these, fluorescence measurement to detect the amount of radiated fluorescence from a biochemical material using a light source, is particularly known to be highly reliable mainly due to its high-speed performance and sensitivity.
  • RT-PCR Fluorescence-based Reaction
  • the fluorescence measurement-based RT-PCR devices are under active researches, and the researches mainly aim to make simple, portable and compact-sized structure which is suitable for application in the point- of-care-testing market and driven at low power consumption and fabricated in cost- effective manner.
  • a light emitting diode (LED) or high sensitivity photodiode is generally adopted to make a compact-sized optical system to measure fluorescence with high sensitivity.
  • Electro-Mechanical Systems technology, epi-fluorescence structure of optical system is generally utilized, and a plurality of sample channels are generally used even for the point-of-care-testing (POCT) case. Even for only one test, measurement cannot be performed smoothly with only one detection channel. Indeed, at least three channels are required to measure the positive, negative and sample simultaneously.
  • sample chambers In LOC, sample chambers, generally in the configuration of a rod, are used to optimize the flow of minute fluid, and the volume of the sample is determined by adjusting the length in the lengthwise direction of the chamber.
  • the volume of the sample In order to increase the efficiency of collecting fluorescence, it is necessary that all rod-like fluorescence patterns be collected in the light detector without cutting, if possible, instead of sampling a certain portion of the fluorescence patterns.
  • magnification optical system it is possible to minimize and measure fluorescence patterns using magnification optical system.
  • a matrix sensor capable of multi-channel detection such as charge coupled device (CCD) or complementary metal oxide semiconductor (CMOS)
  • CCD charge coupled device
  • CMOS complementary metal oxide semiconductor
  • the magnification optical system decreases the size of a plurality of patterns to collect them in the light detector, the intervals of the elongated fluorescence patterns decrease too, making it impossible for a low-price individual photodiode to detect the fluorescence patterns without the use of matrix or array sensor.
  • the recently- introduced light emitting diode (LED) having high brightness can provide increased technological advantages, such as greater power efficiency and longer lifespan.
  • a uniform beam profile of the LED light plays the critical role.
  • a beam ho- mogenizer must be employed to smooth out any irregularities in a light beam profile. Therefore, the addition of the component such as beam homogenizer causes disadvantages such as longer light path, increased unit price, or additional light loss, which can mean serious problems to a minimized optical system.
  • the present invention is provided to resolve the problems occurring in the related art, and therefore, it is an object of the present invention to provide an optical device for multi-chamber fluorescence measurement in a point-of-care-testing (POCT) application, which is compact-sized, portable and thus available for point-of-care-testing (POCT), driven with low power consumption and fabricated at a minimum manufacture cost, and a method for multi-chamber fluorescence measurement using the same.
  • POCT point-of-care-testing
  • POCT point-of-care-testing
  • POCT point-of-care-testing
  • an optical device for multi-chamber fluorescence measurement in a point-of-care-testing (POCT) application which may include a sample processing unit to perform a series of biochemical reactions using an injected sample, a light source to emit a uniform light beam, an excitation light transmitting unit to transfer the light beam emitted from the light source to the sample processing unit, an emission light reducing unit to receive a fluorescence signal emitted from a fluorescence mark of the sample processing unit and output a fluorescence signal in an asymmetrically-reduced form, and a fluorescence detecting unit to detect a fluorescence signal output from the emission light reducing unit.
  • a sample processing unit to perform a series of biochemical reactions using an injected sample
  • a light source to emit a uniform light beam
  • an excitation light transmitting unit to transfer the light beam emitted from the light source to the sample processing unit
  • an emission light reducing unit to receive a fluorescence signal emitted from a fluorescence mark of the sample processing unit
  • the sample processing unit may include a substrate, one or more micro chambers formed inside the sample processing unit to receive a sample or a reaction fluid therein and perform a biochemical reaction, and a micro channel to fluidly connect the micro chambers.
  • the substrate may be made from a plastic, and the micro chambers may be formed in a parallel relation.
  • Each of the micro chambers may be formed in a rod- like shape which has a longer vertical side than a horizontal side.
  • a volume of each of the rod-shaped micro chambers may be adjusted by varying the length in a vertical direction.
  • the sample may include nucleic acid or protein.
  • the light source may include a light emitting diode (LED) array or a LED matrix.
  • LED light emitting diode
  • the excitation light transmitting unit may include one or more of a mask having an identical pattern to the micro chambers of the sample processing unit, a primary optical filter to filter the excitation light from the light source according to an individual wavelength, and a primary lens unit to process the excitation light from the light source.
  • the asymmetric reduction of the emission light reducing unit may include a different reduction rate in a first direction from that in a second direction, in which the first direction is the direction in which a fluorescence signal is emitted from the sample processing unit, and the second direction is the direction perpendicular to the first direction.
  • the emission light reducing unit comprises a dichroic mirror to change a direction of a fluorescence signal emitted from the sample processing unit, a secondary lens unit to process the fluorescence signal, a secondary optical filter to filter the fluorescence signal according to an individual wavelength, and a fluorescence signal converting unit to convert the fluorescence signal into an asymmetrically-reduced form.
  • the fluorescence signal converting unit may be a semi-cylindrical lens or a prism.
  • the fluorescence detecting unit may include one or more photodiodes, and the photodiodes may correspond to micro chambers on a one-to-one basis.
  • a method of using the aforementioned optical device which may include the steps of injecting a sample into a sample processing unit to perform a series of biochemical reactions, emitting a uniform light beam, transferring the light beam emitted from the light source to the sample processing unit, receiving a fluorescence signal emitted from the sample processing unit and outputting an asymmetrically- reduced fluorescence signal, and detecting the asymmetrically-reduced fluorescence signal.
  • the uniform light beam may be formed by a light emitting diode (LED) array or a
  • the step of receiving the fluorescence signal from a fluorescence mark of the sample processing unit and outputting the asymmetrically-reduced fluorescence signal may be performed using a semi-cylindrical lens or a prism.
  • the asymmetric reduction may include a different reduction rate in a first direction from that in a second direction, in which the first direction is the direction in which a fluorescence signal is emitted from the sample processing unit, and the second direction is the direction perpendicular to the first direction.
  • the detecting step may be performed using a photodiode which corresponds to the micro chamber of the sample processing unit.
  • an optical device for multi-chamber fluorescence measurement in a point-of-care-testing (POCT) application is compact-sized, portable and thus available for POCT use, driven with low power consumption and fabricated at a minimum manufacture cost.
  • an optical system for multi-chamber fluorescence measurement in a point-of-care-testing (POCT) application and a method for multi-chamber fluorescence measurement using the same provide advantages such as focusing of fluorescence into a light detector without a light loss, without requiring a high-price imaging device such as a charge coupled device (CCD) or a complementary metal oxide semiconductor (CMOS) even when a sample on a lab- on-a-chip (LOC) has a plurality of rod patterns.
  • a high-price imaging device such as a charge coupled device (CCD) or a complementary metal oxide semiconductor (CMOS) even when a sample on a lab- on-a-chip (LOC) has a plurality of rod patterns.
  • CCD charge coupled device
  • CMOS complementary metal oxide semiconductor
  • an optical system for multi-chamber fluorescence measurement in a point-of-care-testing (POCT) application and a method for multi-chamber fluorescence measurement using the same provide advantages such as minimized light loss and thus regularity in a light beam profile without requiring a separate optical component, by using a light emitting diode (LED) array mixing, and also provide advantage of active dealing with changes in sample patterns on LOC by employing low-power consuming and low-heat generating LED array and a mask in providing light, to maintain uniform lighting pattern.
  • LED light emitting diode
  • FIG. 1 is a conceptual drawing of an optical device for multi-chamber fluorescence measurement in a point-of-care-testing (POCT) application, according to a preferred embodiment of the present invention.
  • POCT point-of-care-testing
  • FIG. 2 illustrates a micro chamber of an optical device for multi-chamber fluorescence measurement in a point-of-care-testing (POCT) application, according to a preferred embodiment of the present invention.
  • POCT point-of-care-testing
  • FIG. 3 is a conceptual view illustrating the length of the chamber being adjusted in a lengthwise direction to adjust the volume of sample received in the micro chamber of FIG. 2.
  • FIG. 4 illustrates the structure of an optical device for multi-chamber fluorescence measurement in a POCT application, according to an exemplary embodiment of the present invention.
  • FIG. 5 schematically illustrates the manner of operation of the emission light reducing unit of the optical device for multi-chamber fluorescence measurement in POCT application according to an exemplary embodiment of the present invention.
  • FIG. 6 illustrates in detail the light source of the optical device for multi-chamber fluorescence measurement in POCT application according to an exemplary embodiment of the present invention.
  • FIG. 1 is a conceptual drawing of an optical device for multi-chamber fluorescence measurement in a point-of-care-testing (POCT) application, according to a preferred embodiment of the present invention.
  • POCT point-of-care-testing
  • the optical device for multi-chamber fluorescence measurement according to the preferred embodiment of the present invention has an epi-fluorescence structure.
  • the optical device for multi-chamber fluorescence measurement may include a light source 11, a fluorescence detecting unit 12, a dichroic mirror 13, a sample processing unit 14, and a micro chamber 15.
  • the excitation light is emitted from the light source 11, and applied to the sample processing unit 14, such as a sample included in the micro chamber 15 on a lab- on-a-chip (LOC).
  • the emission light from the fluorescent mark of the sample passes the dichroic mirror 13 at which the emission light changes its path of travel.
  • the fluorescence detecting unit 12 detects existence or pattern of the emission light.
  • the positions of the light source 11 and the fluorescence detecting unit 12 may be exchanged with each other.
  • FIG. 2 illustrates a micro chamber of an optical device for multi-chamber fluorescence measurement in a point-of-care-testing (POCT) application, according to a preferred embodiment of the present invention.
  • POCT point-of-care-testing
  • the micro chamber 21 are connected with micro channels 22, 23 at opposite ends thereof.
  • the micro chamber 21 may be formed in a variety of patterns, but preferably formed in a rod-shape having longer vertical side (L) than the horizontal side (W).
  • L vertical side
  • W horizontal side
  • FIG. 3 is a conceptual view illustrating the length of the chamber being adjusted in a lengthwise direction to adjust the volumne of sample received in the micro chamber of FIG. 2.
  • the length (L) of the micro chamber is adjusted alone, while the width (W) and height (H) are left unvaried. As explained above, there is a limit on the increase of the width (W) and height (H) for the purpose of ensuring capillarty phenomenon.
  • the ratio of length (L) to width (W) may increase sharply in order to increase the volume of the micro chamber.
  • FIG. 4 illustrates the structure of an optical device for multi-chamber fluorescence measurement in a POCT application, according to an exemplary embodiment of the present invention.
  • the optical device for multi-chamber fluorescence measurement may include a sample processing unit 47, a light source 41, an excitation light transmitting unit 42, 43, 44, 46, an emission light reducing unit 48, 49, 50, 51, and a fluorescence detecting unit 52.
  • the sample processing unit 47 performs a series of biochecmical reactions using the fed sample.
  • the sample processing unit 47 may include a substrate, one or more micro chambers formed therein to receive sample or reaction fluid and perform biochecmical reaction, and a micro channel to fluidly connect the micro chambers.
  • the micro chambers may include a preparing chamber to prepare a sample from a specimen, an amplifying chamber to amplify the sample, an analyzing chamber to which a probe for biological or biochemical reaction with the sample is fixed, a liquid storage chamber to store enzyme or buffer fluid necessary for analysis, or a cleansing chamber to store cleansing liquid necessary for cleansing the other chambers.
  • the micro chambers may be an amplifying chamber of an analyzing chamber.
  • RT-PCR may be performed in one or more of the micro chambers.
  • the substrate may be made from plastic, and the micro chambers may preferably be formed in parallel relation.
  • a micro chamber to detect positive reaction, another chamber to detect negative reaction, and another chamber to detect reaction on the sample may be formed in parallel relation.
  • the micro chambers may preferably be formed in rod-like shape having longer vertical sides than the horizontal sides.
  • each of the micro chamber may additionally include an inlet to which fluid enters, an outlet to which fluid exits, and a micro pump to move the fluid to enter or exit.
  • the sample may take various forms.
  • the sample may contain nucleic acid or protein.
  • the nucleic acid may be selected from a group consisting of DNA, RNA, PNA, LNA and any combination thereof
  • the protein may be selected from a group consisting of enzyme, substrate, antigen, antibody, ligand, aptamer, and receptor.
  • the light source 41 emits uniform light beam.
  • the light source 41 may preferably be a light emitting diode (LED) array or a LED matrix.
  • the present invention overcomes the above-mentioned shortcomings by employing an economic, low-power consuming device such as a LED array as the light source 41 to regulate a light beam profile. Therefore, the device for fluorescence measurement according to the present invention can be compact-sized, economical, and generates less heat.
  • the excitation light transmitting units 42, 43, 44, 46 transmit the light beam emitted from the light source 41 to the sample processing unit 47.
  • the excitation light transmitting units 42, 43, 44, 46 may include a mask 42 having an identical pattern to the micro chamber of the sample processing unit 47, a primary optical filter 43 to filter excitation light beams from the light source 41 according to individual wavelengths, and primary lens units 44, 46 to process the excitation light beam from the light source 41.
  • the emission light reducing units 48, 49, 50, 51 receive fluorescence signal emitted from the fluorescent mark of the sample processing unit 47 and output a fluorescence signal in the asymmetrically-reduced form.
  • the fluorescence signal in the asymmetrically-reduced form may have a different reduction rate in the first direction from that in the second direction, in which the first direction is the direction in which the fluorescence signal is emitted from the sample processing unit, and the second direction is the direction perpendicular to the first direction.
  • the emission light reducing unit may include a dichroic mirror 45 to change a direction of the fluorescence signal being emitted from the sample processing unit 47, a secondary lens unit 48 to process the fluorescence signal, a secondary optical filter 50 to filter the fluorescence signal according to wavelength, and a fluorescence signal converting unit 51 to convert the fluorescence signal into an asymmetrically-reduced signal form.
  • the fluorescence signal converting unit 51 may be a semi-cylindrical lens or a prism.
  • the fluorescence detecting unit 52 detects fluorescence signal output from the emission light reducing unit 48, 49, 50, 51.
  • the fluorescence detecting unit 52 may include one or more photodiodes, which may preferably correspond to the micro chambers of the sample processing unit 47 on a one-to-one basis.
  • the photodiode may preferably be the economic type which includes an amplifier therein.
  • the light source 41 emits a uniform light beam, and the excitation light of the light source 41 is transmitted to the reaction chamber of the sample processing unit 47.
  • the uniform light beam may preferably be formed by a LED array or a LED matrix.
  • the excitation light is passed through the mask 42 having a corresponding pattern to the reaction chamber, then through the filter 43, the dichroic mirror 45, and the lens unit 44, 45, before being applied to the reaction chamber of the sample processing unit 47.
  • the fluorescence signal emitted from the reaction chamber of the sample processing unit 47 changes direction at the dichroic mirror 45 in sequence, to be transmitted to the lens unit 48, the filter 49, 50, and the fluorescence signal converting unit 51.
  • the fluorescence signal of the sample processing unit is received at the signal converting unit 51, which may be a semi-cylindrical lens or a prism, and as a result, a fluorescence signal in an asymmetrically-reduced form is output.
  • the fluorescence signal in the asymmetrically-reduced form may have a different reduction rate in the first direction from that in the second direction, in which the first direction is the direction in which the fluorescence signal is emitted from the sample processing unit, and the second direction is the direction perpendicular to the first direction.
  • the fluorescence signal in the asymmetrically-reduced form is detected.
  • the detection may preferably be performed using a photodiode that corresponds to the micro chamber of the sample processing unit 47.
  • FIG. 5 schematically illustrates the manner of operation of the emission light reducing unit of the optical device for multi-chamber fluorescence measurement in POCT application according to an exemplary embodiment of the present invention.
  • a reference numeral 501 denotes an emission light reducing unit, that is, a signal converting unit.
  • the signal converting unit 501 asymmetrically reduces an input fluorescence signal 502 into an output fluorescence signal 503.
  • an input fluorescence signal 54 may be converted and output as an undesirable output fluorescence signal 55 or a desirable output fluorescence signal 56.
  • the input fluorescence signal 54 includes three fluorescence signals 54a, 54b, 54c of the rod-shaped chamber.
  • the undesirable output fluorescence signal 55 has the length (Lf) and widths (Wf, df) in symmetrically-reduced form, in which case a high-sensitive and high-price CCD or CMOS is required.
  • the desirable output fluorescence signal 56 obtained using the signal converting unit 501 according to the exemplary embodiment of the present invention has the asymmetrically-reduced form, and thus has greatly reduced length (Lf) and the widths (Wf, df) that are barely reduced.
  • the output signals 56a, 56b, 56c are detectable by an individually corresponding low-price photo diode (561, 562, 563).
  • FIG. 6 illustrates in detail the light source of the optical device for multi-chamber fluorescence measurement in POCT application according to an exemplary embodiment of the present invention.
  • the light source includes a substrate 61, and a LED array or matrix 63.
  • a light beam emitted from the LED array or matrix 63 is uniformized through interference each other and thus form a uniform beam region 65 before passing through the mask 62.
  • the uniformized beam then passes through the mask 62 and the lens unit 64.
  • the present invention utilizes an economic, and low-brightness and low-power consuming light source such as LED array to obtain uniformized light beam.
  • the device for measurement according to the present invention provides advantages such as compactness, economic price, and reduced heat generation and power consumption.

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Abstract

An optical device for multi-chamber fluorescence measurement in a point-of-care-testing (POCT) application is provided, which is compact-sized, portable and thus available for POCT use, driven with low power consumption, and fabricated with minimized manufacture cost. The optical device includes a sample processing unit to perform a series of biochemical reaction using an injected sample, a light source to emit a uniform light beam, an excitation light transmitting unit to transfer the light beam emitted from the light source to the sample processing unit, an emission light reducing unit to receive a fluorescence signal emitted from a fluorescence mark of the sample processing unit and output a fluorescence signal in an asymmetrically-reduced form, and a fluorescence detecting unit to detect a fluorescence signal output from the emission light reducing unit.

Description

Description
PORTABLE OPTICAL DEVICE FOR MULTI- CHAMBER FLUORESCENCE MEASUREMENT AND METHOD FOR MULTI- CHAMBER FLUORESCENCE MEASUREMENT USING THE
SAME Technical Field
[1] The present invention relates to a portable optical device for multi-chamber fluorescence measurement and a method for multi-chamber fluorescence measurement using the same. More particularly, the present invention relates to an optical device for multi-chamber fluorescence measurement in a point-of-care testing application, which is compact-sized, portable, and driven with low power consumption and fabricated cost-effectively, and a method for multi-chamber fluorescence measurement using the same. Background Art
[2] A lab-on-a-chip (LOC) is a device that integrates all necessary functionalities conducted in a lab on a bio-chip no larger than a fingernail. This realizes a system that can perform biological analysis fast and cheaply, which will otherwise take a long time and expensive cost, by making microchannels in size not exceeding micro- or nano- liter using materials such as plastics, glasses, or silicons. The LOC has replaced e xperiments or tests that required extensive studies in the lab with an efficient and convenient test that deals with an extremely small amount of sample or feed.
[3] This next-generation diagnostic chip device is capable of detecting cancers, or counting white blood cells or red blood cells based on just a single drop of blood. The LOC is highly value-added, and the use of this technology has expanded variously, for example, in fields such as livestock farming or environment mainly thanks to the rapid advances in biotechnology.
[4] The LOC is even capable of high speed parallel processing, when it is constructed as a multi-channel system. A variety of mechanical, chemical, or electrical ways of measurements can be used to measure biological reaction on a LOC, but among these, fluorescence measurement to detect the amount of radiated fluorescence from a biochemical material using a light source, is particularly known to be highly reliable mainly due to its high-speed performance and sensitivity.
[5] Particularly in fields like gene detection that require Real Time Polymer Chain
Reaction (RT-PCR) to meet the requirements for high speed and sensitive gene detection, the fluorescence measurement is most widely used and commercially available as diagnostic equipments. The fluorescence measurement-based RT-PCR devices are under active researches, and the researches mainly aim to make simple, portable and compact-sized structure which is suitable for application in the point- of-care-testing market and driven at low power consumption and fabricated in cost- effective manner.
[6] A light emitting diode (LED) or high sensitivity photodiode is generally adopted to make a compact-sized optical system to measure fluorescence with high sensitivity.
[7] However, since the geometry of optical system is heavily dependent on the ways to heat/cool a sample chamber, to control fluid flow, or to feed sample, the structure of the optical system or optical components are determined individually according to the configuration or structure of the sample chamber.
[8] Particularly in the case of a planar LOC that employs plastic Micro-
Electro-Mechanical Systems (MEMS) technology, epi-fluorescence structure of optical system is generally utilized, and a plurality of sample channels are generally used even for the point-of-care-testing (POCT) case. Even for only one test, measurement cannot be performed smoothly with only one detection channel. Indeed, at least three channels are required to measure the positive, negative and sample simultaneously.
[9] In LOC, sample chambers, generally in the configuration of a rod, are used to optimize the flow of minute fluid, and the volume of the sample is determined by adjusting the length in the lengthwise direction of the chamber. In order to increase the efficiency of collecting fluorescence, it is necessary that all rod-like fluorescence patterns be collected in the light detector without cutting, if possible, instead of sampling a certain portion of the fluorescence patterns.
[10] Meanwhile, it is possible to minimize and measure fluorescence patterns using magnification optical system. However, this method requires that a matrix sensor capable of multi-channel detection, such as charge coupled device (CCD) or complementary metal oxide semiconductor (CMOS), be employed to detect signals from a plurality of channels simultaneously. When the magnification optical system decreases the size of a plurality of patterns to collect them in the light detector, the intervals of the elongated fluorescence patterns decrease too, making it impossible for a low-price individual photodiode to detect the fluorescence patterns without the use of matrix or array sensor. Even if the array sensor is employed, it is then necessary to employ complicated electric circuit structure and high-price array sensor to maintain high sensitivity, and thus is inappropriate for POCT application. Meanwhile, the recently- introduced light emitting diode (LED) having high brightness can provide increased technological advantages, such as greater power efficiency and longer lifespan. However, as mentioned above, in order to utilize the LED in LOC as a light source to irradiate a light beam onto a sample having a predetermined area or pattern, a uniform beam profile of the LED light plays the critical role. In other words, a beam ho- mogenizer must be employed to smooth out any irregularities in a light beam profile. Therefore, the addition of the component such as beam homogenizer causes disadvantages such as longer light path, increased unit price, or additional light loss, which can mean serious problems to a minimized optical system.
[H]
Disclosure of Invention Technical Problem
[12] The present invention is provided to resolve the problems occurring in the related art, and therefore, it is an object of the present invention to provide an optical device for multi-chamber fluorescence measurement in a point-of-care-testing (POCT) application, which is compact-sized, portable and thus available for point-of-care-testing (POCT), driven with low power consumption and fabricated at a minimum manufacture cost, and a method for multi-chamber fluorescence measurement using the same.
[13] It is another object of the present invention to provide an optical system for multi- chamber fluorescence measurement in a point-of-care-testing (POCT) application, which is capable of focusing fluorescence into a light detector efficiently without a loss of light, without requiring a high-price imaging device such as a charge coupled device (CCD) or a complementary metal oxide semiconductor (CMOS) even when a sample on a lab-on-a-chip (LOC) has a plurality of rod patterns, and a method for multi- chamber fluorescence measurement using the same.
[14] It is yet another object of the present invention to provide an optical system for multi-chamber fluorescence measurement in a point-of-care-testing (POCT) application, which is capable of minimizing light loss and thus ensuring regularity in a light beam profile without requiring a separate optical component, since the optical system uses a light emitting diode (LED) array mixing, and is also capable of actively dealing with changes in sample patterns on LOC by employing low-power consuming and low-heat generating LED array and a mask in providing light, to maintain uniform lighting pattern, and a method of using the same. Technical Solution
[15] In order to achieve the objects of the present invention, there is provided an optical device for multi-chamber fluorescence measurement in a point-of-care-testing (POCT) application, which may include a sample processing unit to perform a series of biochemical reactions using an injected sample, a light source to emit a uniform light beam, an excitation light transmitting unit to transfer the light beam emitted from the light source to the sample processing unit, an emission light reducing unit to receive a fluorescence signal emitted from a fluorescence mark of the sample processing unit and output a fluorescence signal in an asymmetrically-reduced form, and a fluorescence detecting unit to detect a fluorescence signal output from the emission light reducing unit.
[16] The sample processing unit may include a substrate, one or more micro chambers formed inside the sample processing unit to receive a sample or a reaction fluid therein and perform a biochemical reaction, and a micro channel to fluidly connect the micro chambers.
[17] The substrate may be made from a plastic, and the micro chambers may be formed in a parallel relation.
[18] Each of the micro chambers may be formed in a rod- like shape which has a longer vertical side than a horizontal side.
[19] A volume of each of the rod-shaped micro chambers may be adjusted by varying the length in a vertical direction.
[20] The sample may include nucleic acid or protein.
[21] The light source may include a light emitting diode (LED) array or a LED matrix.
[22] The excitation light transmitting unit may include one or more of a mask having an identical pattern to the micro chambers of the sample processing unit, a primary optical filter to filter the excitation light from the light source according to an individual wavelength, and a primary lens unit to process the excitation light from the light source.
[23] The asymmetric reduction of the emission light reducing unit may include a different reduction rate in a first direction from that in a second direction, in which the first direction is the direction in which a fluorescence signal is emitted from the sample processing unit, and the second direction is the direction perpendicular to the first direction.
[24] The emission light reducing unit comprises a dichroic mirror to change a direction of a fluorescence signal emitted from the sample processing unit, a secondary lens unit to process the fluorescence signal, a secondary optical filter to filter the fluorescence signal according to an individual wavelength, and a fluorescence signal converting unit to convert the fluorescence signal into an asymmetrically-reduced form.
[25] The fluorescence signal converting unit may be a semi-cylindrical lens or a prism.
[26] The fluorescence detecting unit may include one or more photodiodes, and the photodiodes may correspond to micro chambers on a one-to-one basis.
[27] According to an exemplary embodiment of the present invention, there also is provided a method of using the aforementioned optical device, which may include the steps of injecting a sample into a sample processing unit to perform a series of biochemical reactions, emitting a uniform light beam, transferring the light beam emitted from the light source to the sample processing unit, receiving a fluorescence signal emitted from the sample processing unit and outputting an asymmetrically- reduced fluorescence signal, and detecting the asymmetrically-reduced fluorescence signal.
[28] The uniform light beam may be formed by a light emitting diode (LED) array or a
LED matrix.
[29] The step of receiving the fluorescence signal from a fluorescence mark of the sample processing unit and outputting the asymmetrically-reduced fluorescence signal, may be performed using a semi-cylindrical lens or a prism.
[30] The asymmetric reduction may include a different reduction rate in a first direction from that in a second direction, in which the first direction is the direction in which a fluorescence signal is emitted from the sample processing unit, and the second direction is the direction perpendicular to the first direction.
[31] The detecting step may be performed using a photodiode which corresponds to the micro chamber of the sample processing unit.
Advantageous Effects
[32] According to the present invention, an optical device for multi-chamber fluorescence measurement in a point-of-care-testing (POCT) application is compact-sized, portable and thus available for POCT use, driven with low power consumption and fabricated at a minimum manufacture cost.
[33] Furthermore, according to the present invention, an optical system for multi-chamber fluorescence measurement in a point-of-care-testing (POCT) application and a method for multi-chamber fluorescence measurement using the same, provide advantages such as focusing of fluorescence into a light detector without a light loss, without requiring a high-price imaging device such as a charge coupled device (CCD) or a complementary metal oxide semiconductor (CMOS) even when a sample on a lab- on-a-chip (LOC) has a plurality of rod patterns.
[34] Furthermore, according to the present invention, an optical system for multi-chamber fluorescence measurement in a point-of-care-testing (POCT) application and a method for multi-chamber fluorescence measurement using the same, provide advantages such as minimized light loss and thus regularity in a light beam profile without requiring a separate optical component, by using a light emitting diode (LED) array mixing, and also provide advantage of active dealing with changes in sample patterns on LOC by employing low-power consuming and low-heat generating LED array and a mask in providing light, to maintain uniform lighting pattern.
[35]
[36] [Brief explanation of the drawings] [37] FIG. 1 is a conceptual drawing of an optical device for multi-chamber fluorescence measurement in a point-of-care-testing (POCT) application, according to a preferred embodiment of the present invention.
[38] FIG. 2 illustrates a micro chamber of an optical device for multi-chamber fluorescence measurement in a point-of-care-testing (POCT) application, according to a preferred embodiment of the present invention.
[39] FIG. 3 is a conceptual view illustrating the length of the chamber being adjusted in a lengthwise direction to adjust the volume of sample received in the micro chamber of FIG. 2.
[40] FIG. 4 illustrates the structure of an optical device for multi-chamber fluorescence measurement in a POCT application, according to an exemplary embodiment of the present invention.
[41] FIG. 5 schematically illustrates the manner of operation of the emission light reducing unit of the optical device for multi-chamber fluorescence measurement in POCT application according to an exemplary embodiment of the present invention.
[42] FIG. 6 illustrates in detail the light source of the optical device for multi-chamber fluorescence measurement in POCT application according to an exemplary embodiment of the present invention.
[43]
Best Mode for Carrying Out the Invention
[44] The present invention will be explained below with reference to the accompanying drawings.
[45] FIG. 1 is a conceptual drawing of an optical device for multi-chamber fluorescence measurement in a point-of-care-testing (POCT) application, according to a preferred embodiment of the present invention.
[46] Referring to FIG. 1, the optical device for multi-chamber fluorescence measurement according to the preferred embodiment of the present invention has an epi-fluorescence structure.
[47] According to the preferred embodiment of the present invention, the optical device for multi-chamber fluorescence measurement may include a light source 11, a fluorescence detecting unit 12, a dichroic mirror 13, a sample processing unit 14, and a micro chamber 15.
[48] The excitation light is emitted from the light source 11, and applied to the sample processing unit 14, such as a sample included in the micro chamber 15 on a lab- on-a-chip (LOC). The emission light from the fluorescent mark of the sample passes the dichroic mirror 13 at which the emission light changes its path of travel. The fluorescence detecting unit 12 detects existence or pattern of the emission light. The positions of the light source 11 and the fluorescence detecting unit 12 may be exchanged with each other.
[49] FIG. 2 illustrates a micro chamber of an optical device for multi-chamber fluorescence measurement in a point-of-care-testing (POCT) application, according to a preferred embodiment of the present invention.
[50] Referring to FIG. 2, the micro chamber 21 are connected with micro channels 22, 23 at opposite ends thereof.
[51] The micro chamber 21 may be formed in a variety of patterns, but preferably formed in a rod-shape having longer vertical side (L) than the horizontal side (W). By forming a rod-like micro chamber, capillary phenomenon may facilitate movement of minute fluid, which leads to optimization of the flow of minute fluid.
[52] FIG. 3 is a conceptual view illustrating the length of the chamber being adjusted in a lengthwise direction to adjust the volumne of sample received in the micro chamber of FIG. 2.
[53] Referring to FIG. 3, the length (L) of the micro chamber is adjusted alone, while the width (W) and height (H) are left unvaried. As explained above, there is a limit on the increase of the width (W) and height (H) for the purpose of ensuring capillarty phenomenon. The ratio of length (L) to width (W) may increase sharply in order to increase the volume of the micro chamber.
[54] It is very preferable to collect the whole rod-like fluorescence patterns generated in the micro chamber to the light detector, instead of sampling a certain portion for measurement, in order to detect the existence of a target material or biochemical reaction that may occur in the rod- shaped micro chamber.
[55] To this end, it may be possible to reduce the rod-like fluorescence patterns for measurement using a magnification optical system. However, this method requires that a matrix sensor capable of multi-channel detection, such as charge coupled device (CCD) or complementary metal oxide semiconductor (CMOS), be employed to detect signals from a plurality of channels. If the device such as CCD or CMOS is employed, it is necessary to employ complicated electric circuit structure and high-price array sensor to maintain high sensitivity, and since the volume of the system increases to house the additional component, it is inappropriate for POCT application.
[56] FIG. 4 illustrates the structure of an optical device for multi-chamber fluorescence measurement in a POCT application, according to an exemplary embodiment of the present invention.
[57] The optical device for multi-chamber fluorescence measurement will be explained in greater detail below with reference to FIG. 4.
[58] Referring to FIG. 4, the optical device for multi-chamber fluorescence measurement according to the exemplary embodiment of the present invention may include a sample processing unit 47, a light source 41, an excitation light transmitting unit 42, 43, 44, 46, an emission light reducing unit 48, 49, 50, 51, and a fluorescence detecting unit 52.
[59] The sample processing unit 47 performs a series of biochecmical reactions using the fed sample.
[60] The sample processing unit 47 may include a substrate, one or more micro chambers formed therein to receive sample or reaction fluid and perform biochecmical reaction, and a micro channel to fluidly connect the micro chambers.
[61] For example, the micro chambers may include a preparing chamber to prepare a sample from a specimen, an amplifying chamber to amplify the sample, an analyzing chamber to which a probe for biological or biochemical reaction with the sample is fixed, a liquid storage chamber to store enzyme or buffer fluid necessary for analysis, or a cleansing chamber to store cleansing liquid necessary for cleansing the other chambers. Preferably, the micro chambers may be an amplifying chamber of an analyzing chamber. For example, RT-PCR may be performed in one or more of the micro chambers.
[62] The substrate may be made from plastic, and the micro chambers may preferably be formed in parallel relation. For example, in order to detect a target within the sample, a micro chamber to detect positive reaction, another chamber to detect negative reaction, and another chamber to detect reaction on the sample, may be formed in parallel relation.
[63] As explained above, the micro chambers may preferably be formed in rod-like shape having longer vertical sides than the horizontal sides.
[64] According to the present invention, each of the micro chamber may additionally include an inlet to which fluid enters, an outlet to which fluid exits, and a micro pump to move the fluid to enter or exit.
[65] According to the present invention, the sample may take various forms. For example, the sample may contain nucleic acid or protein. The nucleic acid may be selected from a group consisting of DNA, RNA, PNA, LNA and any combination thereof, and the protein may be selected from a group consisting of enzyme, substrate, antigen, antibody, ligand, aptamer, and receptor.
[66] The light source 41 emits uniform light beam. The light source 41 may preferably be a light emitting diode (LED) array or a LED matrix.
[67] In detecting fluorescence on LOC, emitting a uniform light beam plays a critical role.
Conventionally, a beam homogenizer or a light pipe is used to regulate the light beam profile. While the conventional method can obtain uniform light beam profile, the method also has shortcomings. That is, the above device is expensive, increases light path and thus takes large volume of space and causes additional light loss. Accordingly, the conventional method is inappropriate for the POCT application. [68] The present invention overcomes the above-mentioned shortcomings by employing an economic, low-power consuming device such as a LED array as the light source 41 to regulate a light beam profile. Therefore, the device for fluorescence measurement according to the present invention can be compact-sized, economical, and generates less heat.
[69] The excitation light transmitting units 42, 43, 44, 46 transmit the light beam emitted from the light source 41 to the sample processing unit 47.
[70] The excitation light transmitting units 42, 43, 44, 46 may include a mask 42 having an identical pattern to the micro chamber of the sample processing unit 47, a primary optical filter 43 to filter excitation light beams from the light source 41 according to individual wavelengths, and primary lens units 44, 46 to process the excitation light beam from the light source 41.
[71] The emission light reducing units 48, 49, 50, 51 receive fluorescence signal emitted from the fluorescent mark of the sample processing unit 47 and output a fluorescence signal in the asymmetrically-reduced form. The fluorescence signal in the asymmetrically-reduced form may have a different reduction rate in the first direction from that in the second direction, in which the first direction is the direction in which the fluorescence signal is emitted from the sample processing unit, and the second direction is the direction perpendicular to the first direction.
[72] The emission light reducing unit may include a dichroic mirror 45 to change a direction of the fluorescence signal being emitted from the sample processing unit 47, a secondary lens unit 48 to process the fluorescence signal, a secondary optical filter 50 to filter the fluorescence signal according to wavelength, and a fluorescence signal converting unit 51 to convert the fluorescence signal into an asymmetrically-reduced signal form.
[73] The fluorescence signal converting unit 51 may be a semi-cylindrical lens or a prism.
It is possible to vary the reduction rate and the asymmetric reduction rate of the fluorescence signal converting unit 51 according to the size of the chamber, and the rate of horizontal to vertical lengths of the chamber.
[74] The fluorescence detecting unit 52 detects fluorescence signal output from the emission light reducing unit 48, 49, 50, 51.
[75] The fluorescence detecting unit 52 may include one or more photodiodes, which may preferably correspond to the micro chambers of the sample processing unit 47 on a one-to-one basis. The photodiode may preferably be the economic type which includes an amplifier therein.
[76] Referring to FIG. 4, the operation of the optical device for multi-chamber fluorescence measurement in POCT application, and a method for multi-chamber fluorescence measurement using the same according to the exemplary embodiment of the present invention will be explained in greater detail below.
[77] First, a sample is injected into the sample processing unit 47 to undergo a series of biochemical reactions. Next, a series of processes are performed as explained below to analyze the result of the reactions.
[78] The light source 41 emits a uniform light beam, and the excitation light of the light source 41 is transmitted to the reaction chamber of the sample processing unit 47. The uniform light beam may preferably be formed by a LED array or a LED matrix.
[79] Accordingly, the excitation light is passed through the mask 42 having a corresponding pattern to the reaction chamber, then through the filter 43, the dichroic mirror 45, and the lens unit 44, 45, before being applied to the reaction chamber of the sample processing unit 47.
[80] Next, the fluorescence signal emitted from the reaction chamber of the sample processing unit 47 changes direction at the dichroic mirror 45 in sequence, to be transmitted to the lens unit 48, the filter 49, 50, and the fluorescence signal converting unit 51.
[81] Accordingly, the fluorescence signal of the sample processing unit is received at the signal converting unit 51, which may be a semi-cylindrical lens or a prism, and as a result, a fluorescence signal in an asymmetrically-reduced form is output. The fluorescence signal in the asymmetrically-reduced form may have a different reduction rate in the first direction from that in the second direction, in which the first direction is the direction in which the fluorescence signal is emitted from the sample processing unit, and the second direction is the direction perpendicular to the first direction.
[82] Next, the fluorescence signal in the asymmetrically-reduced form is detected. The detection may preferably be performed using a photodiode that corresponds to the micro chamber of the sample processing unit 47.
[83] FIG. 5 schematically illustrates the manner of operation of the emission light reducing unit of the optical device for multi-chamber fluorescence measurement in POCT application according to an exemplary embodiment of the present invention.
[84] On the top side of FIG. 5, a reference numeral 501 denotes an emission light reducing unit, that is, a signal converting unit. The signal converting unit 501 asymmetrically reduces an input fluorescence signal 502 into an output fluorescence signal 503.
[85] As shown below the top side of FIG. 5, an input fluorescence signal 54 may be converted and output as an undesirable output fluorescence signal 55 or a desirable output fluorescence signal 56. The input fluorescence signal 54 includes three fluorescence signals 54a, 54b, 54c of the rod-shaped chamber.
[86] The undesirable output fluorescence signal 55 has the length (Lf) and widths (Wf, df) in symmetrically-reduced form, in which case a high-sensitive and high-price CCD or CMOS is required.
[87] On the contrary, the desirable output fluorescence signal 56 obtained using the signal converting unit 501 according to the exemplary embodiment of the present invention has the asymmetrically-reduced form, and thus has greatly reduced length (Lf) and the widths (Wf, df) that are barely reduced. In this case, it is advantageous since the output signals 56a, 56b, 56c are detectable by an individually corresponding low-price photo diode (561, 562, 563).
[88] FIG. 6 illustrates in detail the light source of the optical device for multi-chamber fluorescence measurement in POCT application according to an exemplary embodiment of the present invention.
[89] Referring to FIG. 6, the light source includes a substrate 61, and a LED array or matrix 63. A light beam emitted from the LED array or matrix 63 is uniformized through interference each other and thus form a uniform beam region 65 before passing through the mask 62. The uniformized beam then passes through the mask 62 and the lens unit 64.
[90] As explained above, instead of one high-brightness LED and beam homogenizer or light pipe, which are expensive and take large space, the present invention utilizes an economic, and low-brightness and low-power consuming light source such as LED array to obtain uniformized light beam. As a result, the device for measurement according to the present invention provides advantages such as compactness, economic price, and reduced heat generation and power consumption.
[91] While the invention has been shown and described with reference to certain embodiments to carry out this invention, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims.
[92]

Claims

Claims
[1] An optical device for multi-chamber fluorescence measurement in a point- of-care-testing (POCT) application, the optical device comprising: a sample processing unit to perform a series of biochemical reactions using an injected sample; a light source to emit a uniform light beam; an excitation light transmitting unit to transfer the light beam emitted from the light source to the sample processing unit; an emission light reducing unit to receive a fluorescence signal emitted from a fluorescence mark of the sample processing unit and output a fluorescence signal in an asymmetrically-reduced form; and a fluorescence detecting unit to detect a fluorescence signal output from the emission light reducing unit.
[2] The optical device according to claim 1, wherein the sample processing unit comprises a substrate; one or more micro chambers formed inside the sample processing unit to receive a sample or a reaction fluid therein and perform a biochemical reaction; and a micro channel to fluidly connect the micro chambers.
[3] The optical device according to claim 2, wherein the substrate is made from a plastic, and the micro chambers are formed in a parallel relation.
[4] The optical device according to claim 2, wherein each of the micro chambers is formed in a rod-like shape which has a longer vertical side than a horizontal side.
[5] The optical device according to claim 4, wherein a volume of each of the rod- shaped micro chambers is adjusted by varying the length in a vertical direction.
[6] The optical device according to claim 1, wherein the sample comprises nucleic acid or protein.
[7] The optical device according to claim 1, wherein the light source comprises a light emitting diode (LED) array or a LED matrix.
[8] The optical device according to claim 1, wherein the excitation light transmitting unit comprises one or more of: a mask having an identical pattern to the micro chambers of the sample processing unit; a primary optical filter to filter the excitation light from the light source according to an individual wavelength; and a primary lens unit to process the excitation light from the light source.
[9] The optical device according to claim 1, wherein the asymmetric reduction of the emission light reducing unit comprises a different reduction rate in a first direction from that in a second direction, in which the first direction is the direction in which a fluorescence signal is emitted from the sample processing unit, and the second direction is the direction perpendicular to the first direction.
[10] The optical device according to claim 1, wherein the emission light reducing unit comprises one or more of: a dichroic mirror to change a direction of a fluorescence signal emitted from the sample processing unit; a secondary lens unit to process the fluorescence signal; a secondary optical filter to filter the fluorescence signal according to an individual wavelength; and a fluorescence signal converting unit to convert the fluorescence signal into an asymmetrically-reduced form.
[11] The optical device according to claim 10, wherein the fluorescence signal converting unit is a semi-cylindrical lens or a prism.
[12] The optical device according to claim 1, wherein the fluorescence detecting unit comprises one or more photodiodes which correspond to micro chambers on a one-to-one basis.
[13] A method for multi-chamber fluorescence measurement using an optical device according to any one of claims 1 to 11, the method comprising the steps of: injecting a sample into a sample processing unit to perform a series of biochemical reactions; emitting a uniform light beam; transferring the light beam emitted from the light source to the sample processing unit; receiving a fluorescence signal emitted from the sample processing unit and outputting an asymmetrically-reduced fluorescence signal; and detecting the asymmetrically-reduced fluorescence signal.
[14] The method according to claim 13, wherein the uniform light beam is formed by a light emitting diode (LED) array or a LED matrix.
[15] The method according to claim 13, wherein the step of receiving the fluorescence signal from a fluorescence mark of the sample processing unit and outputting the asymmetrically-reduced fluorescence signal, is performed using a semi- cylindrical lens or a prism.
[16] The method according to claim 13, wherein the asymmetric reduction comprises a different reduction rate in a first direction from that in a second direction, in which the first direction is the direction in which a fluorescence signal is emitted from the sample processing unit, and the second direction is the direction perpendicular to the first direction. [17] The method according to claim 13, wherein the detecting step is performed using a photodiode which corresponds to the micro chamber of the sample processing unit.
PCT/KR2008/006108 2007-10-16 2008-10-16 Portable optical device for multi-chamber fluorescence measurement and method for multi-chamber fluorescence measurement using the same WO2009051416A1 (en)

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