CN103196874A - Aggregation-induced emission (AIE) illuminant Cbased urine protein detection device for monitoring health of people - Google Patents
Aggregation-induced emission (AIE) illuminant Cbased urine protein detection device for monitoring health of people Download PDFInfo
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Abstract
The invention relates to a portable urine protein detection device which uses an aggregation-induced emission (AIE) illuminant to detect one or more urine proteins and quantitate total urine protein in a urine sample so as to monitor health of people. The invention particularly relates to a device, the device uses a water-soluble AIE illuminant to detect one or more urine proteins so as to determine the content of target protein and total urine protein in a tested object. The device can be used in household or clinical environment, and is used for monitoring health of people at regular intervals.
Description
The cross reference of related application
According to 35 U.S.C. § 119 (e), the present invention is non-provisional application, and it requires the rights and interests of the U.S. Provisional Application 61/631,661 of submission on January 9th, 2012, and the disclosure of described U.S. Provisional Application is incorporated herein by reference.
Technical field
The present invention relates to a kind of portable urine Protein Detection device, it utilizes aggregation inducing photism (AIE) shiner to detect urine albumen and the total urinary protein in the urine samples is carried out quantitatively, so that monitor's health.Relate in particular to and a kind ofly utilize water-soluble AIE shiner to detect one or more urine albumen in order to measure target protein in the study subject and the device of the content of total urinary protein.Described device can use in family or clinical setting, is used for regular monitoring people's health.
Background technology
Unless many human diseasess have arrived period very late, otherwise are not easy to be diagnosed out, because its physiological signs is not obvious.The slight variation of body fluid component can mean in the body and go wrong that therefore, detecting the body fluid composition is to be even more important.Urine is often used as biological marker in diagnostics and the clinical research, because it is the body fluid that can easily obtain from non-invasive mode.
Protein in the urine and the complex mixture of peptide can reflect serum composition and renal function.Occur excess protein caution in the urine and chronic disease occurred, for example diabetes, problem that hypertension is relevant with the kidney inflammation etc.Nowadays, colorimetric method such as Bradford (Brandford) and Lip river auspicious (Lowry) analysis etc. that much are used for the protein of volumetric soiutions are developed.Yet these methods generally lack sensitivity and accuracy, and program is loaded down with trivial details.The most of urine test sheet (urine-testing dipstick) that can be used as monitoring every day urine albumen of summarizing all utilizes and is soaked with pH susceptibility dyestuff.For the main protein human serum albumins (HSA) in the urine, the detection threshold of urine test sheet can reach 100-200mg/L, but the protein concentration in healthy people's the normal urine is less than 30mg/L, and visible urine test sheet is obviously sensitive inadequately, is not enough to analyze ephrosis.Therefore exploitation detects with quantitative effective ways the urine albumen of low concentration and has clinical value.
Based on graceful function, sensitivity, selectivity and rapidity, the protein biosensor of fluorescence organic substance has attracted a lot of concerns.The thorny problem that conventional shiner runs into usually is to assemble cancellation (the aggregation-caused quenching that causes; ACQ).When they were dispersed in the aqueous medium or are incorporated on the protein in the buffer solution, these molecules tended to assemble, and this can its fluorescence of cancellation and therefore greatly limits it as the effective range of bioprobe.We have had been found that a kind of special aggregation inducing luminous (AIE) phenomenon recently, itself and ACQ effect complete opposite (U.S. Patent number 7,939,613,8,129,111 and 8,263,018; U.S. Patent Application Publication No. 2012/0172296A1, its disclosure is incorporated this paper by reference into).Opposite with cancellation, assemble counter some propeller-like mulecular luminescence that makes, make described molecule become strong luminophor by hypofluorescence group.Tetraphenyl ethene (TPE) is a kind of in this class AIE shiner, and has high-fluorescence quantum yield, easy synthetic and easy functionalized advantage.TPE with sulfonated functional group produces soluble derivative, and it can be used as the unlatching fluorescence probe (turn-on fluorescent probe) of HSA.Under the HSA concentration range of 0-100mg/L, fluorescence intensity is linear to be increased in artificial urine, and detectability can be down to the low 1mg/L that reaches.Except having good sensitivity, fluorophore shows splendid selectivity to HSA in different protein and DNA.These breathtaking results inspire us further to explore its clinical practice.In the present invention, disclose a kind of low cost, portable and technical simple multichannel urine albumen device, it has high sensitivity based on the AIE fluorescent technique.Described device can be extensive use of in family and clinic, in order to monitor health status every day.
Summary of the invention
A first aspect of the present invention relates to the device that a kind of AIE of use shiner detects the target protein in the urine samples.Device of the present invention mainly comprises housing, light source, is used for holding sampling receptacle, cell holder, photodetector, signal amplifier, output element and the integrated circuit related with same of urine samples.Light source, cell holder, photodetector, signal amplifier and integrated circuit are closed in the housing, described housing is configured for the fluorescence signal from the compound of AIE shiner and target protein is being carried out avoiding the background signal from exterior light between detection period.Light source is bright as much as possible, and all size of component are less relatively in order to allow device to carry easily in the device.The principle of work of described device is to utilize exciting of narrow bandwidth light source to make the compound of target protein in the urine samples and AIE shiner produce fluorescence signal, and with fluorescence signal with compare at the predetermined reference value of artificial urine samples, so that the target protein content in the mensuration urine samples, thereby measure total urinary protein.Described device can provide the qualitative and quantitative data output corresponding to target protein content.Working range for urine albumen is 0-300mg/L, and detects limit value and can hang down and reach 5mg/L.Yet concentration adjustment working range that can be by regulating the AIE shiner is so that the range of linearity is fit to the molecule tested.
A second aspect of the present invention relates to the method that a kind of use detects the urine albumen in the urine samples based on the described device of the principle of AIE shiner and measures total urinary protein.Described method comprises: preparation contains the solution of AIE compound, solution is placed in advance in the sampling receptacle of the described device of being fixed by cell holder, urine samples is injected in the sampling receptacle, container is exposed in the light that is produced by light source, detection is from the fluorescence signal of AIE shiner-target protein compound emission, convert fluorescence signal to voltage, measuring voltage, with relatively the voltage of surveying with at artificial urine samples under different target protein concentration predetermined reference value with the target protein content in the quantitative urine samples with based on target protein assay total urinary protein.If the electric signal that converts from fluorescence signal reaches starting voltage, so described signal also can be used for opening other output element, therefore can produce qualitative output signal, for example light signal or voice signal.When beginning to detect fluorescent emission, the qualitative and quantitative output of described device nearly all is instant.
Description of drawings
Fig. 1 is the molecular structure of the different water-soluble AIE shiner of the present invention's use.
Fig. 2: (A) fluorescence (FL) spectrum of compound 1 (SATPE) in the phosphate buffer (PBS) of the HSA that contains variable concentrations; (B) under 475nm FL intensity with the variation of HSA concentration; The FL intensity of I0=under the situation that does not have HSA.Illustration: SATPE and HSA in conjunction with the isothermal range of linearity.[SATPE]＝5μM；λ
ex＝350nm。
Fig. 3: (A) HSA in artificial urine and PBS damping fluid and SATPE's in conjunction with isotherm; (B) under 475nm the FL intensity of SATPE to the dependence of the different proteins in artificial urine and the PBS damping fluid.[SATPE]=5 μ M; [protein]=100 μ g/mL; λ
Ex=350nm.
Fig. 4 is the process flow diagram of how to work about urine Protein Detection device.
Fig. 5 is the block diagram of the integrated circuit of urine Protein Detection device.
Fig. 6 is the emission spectrum of the UV led light source that uses among the present invention.
Fig. 7 is the vertical view of an embodiment of urine Protein Detection device.
Fig. 8: (A) voltage is to the dependence of the different HSA concentration in the artificial urine of urine albumen device and the SATPE potpourri; (B) at the voltage of the different HSA concentration standardizations in the artificial urine.[SATPE]＝10mM
Embodiment
Definition
Provide to give a definition and also be used for constituting the patent claims of enclosing to be used for understanding theme of the present invention.
Unless should be understood that context clearly indication is arranged in addition, used singulative " " and " described " comprises a plurality of references object in this instructions and the claims of enclosing.
" aggregation inducing is luminous " or abbreviation " ALE " meaning are to be unlocked when aggregation forms or at solid-state fluorescent/phosphorescent down.When molecular level dissolves, the material with this character does not have photism.Yet, when rotation in the molecule is limited, luminous unlatching.
" cancellation that gathering causes " or abbreviation " ACQ " meaning are by cancellation when aggregation forms or at solid-state time fluorescent/phosphorescent.When shiner when molecular level is dissolved in the solution, it can be luminous.
" emissive porwer " meaning is the value of the fluorescent/phosphorescent that usually obtains from fluorescence spectrometer, fluorescence microscopy measurement mechanism.
Unless otherwise defined, otherwise the common implication of understanding of those skilled in the art in the field under the theme that the implication of all scientific and technical terms used herein and the present invention describe is identical.
Unless otherwise indicated, otherwise used all chemical substances of the application all available from Sigma-Aldrich.Before closing on use, under drying nitrogen, from benzophenone sodium ketyl (sodium benzophenone ketyl), distill THF.Water carries out purifying by the Millipore filtering system.Artificial urine is to prepare and sterilize in pressure cooker before using closing on.
On Bruker AV 300 spectrometers, use in tetramethylsilane (TMS, the δ=0) conduct and be marked on CDCl
3The middle measurement
1H and
13C NMR spectrum.High resolution mass spec (HRMS) is recorded on the GCT premier CAB048 mass spectrometer with the work of MALDI-TOF pattern.Emission spectrum is recorded on Perkin-Elmer LS 55 fluorescence spectrometers.
Term " shiner " and " fluorophore " are used interchangeably in this article, refer to launch the fluorescent dye of the AIE compound of about 470-475nm fluorescence signal under the exciting of the UV of the about 350-355nm of peak value light.
Water-soluble AIE shiner of the present invention has the skeleton of following any chemical formula:
R wherein
1Combined thing (X) independently
nSO
3 -Na
+Replace, wherein X is selected from alkyl, unsaturated alkyl, assorted alkyl, naphthenic base, Heterocyclylalkyl, aryl or heteroaryl, and n=0 to 20 wherein.
Fig. 1 shows four embodiments of water-soluble AIE shiner, i.e. compound 1-4.Compound 1-4 prepares according to the route of synthesis shown in the following scheme 1-4 respectively:
The route of synthesis of scheme 1. synthesizing water-solubility AIE compounds 1:
The route of synthesis of scheme 2. synthesizing water-solubility AIE compounds 2:
The route of synthesis of scheme 3. synthesizing water-solubility AIE compounds 3:
The route of synthesis of scheme 4. synthesizing water-solubility AIE compounds 4:
In the first embodiment, carry out the McMurry coupling by making the 4-dihydroxy benaophenonel, subsequently by with 1,3-propane sultone (1,3-propansultone) carry out nucleophilic displacement of fluorine and obtain compound 1.By recrystallization in acetone 1 crude product is carried out purifying.
In second embodiment, under the situation that has copper sulphate (II) and sodium ascorbate, make two [4-(azido-methyl) phenyl]-1 of 1,2-, 2-diphenylethlene and third-2-alkynes-1-sodium sulfonate carry out " click " reaction and come synthetic compound 2.By using methyl alcohol to separate final product as the column chromatography of eluant, eluent.
In the 3rd embodiment, by using boron trifluoride dimethyl sulfide compound two (4-methoxyphenyl) anti-maleic nitriles of 2,3-are gone protection, use 1,3-propane sultone to carry out nucleophilic displacement of fluorine subsequently and obtain compound 3.Come purified product by recrystallization in acetone.
In the 4th embodiment, use copper sulphate (II) and sodium ascorbate as catalyzer, make two (4-(azido-methyl) phenyl)-1 of 2,5-, 1-dimethyl-3,4-diphenyl-thiophene are coughed up (silole) and third-2-alkynes-1-sodium sulfonate and are carried out " clicks " and react and prepare compound 4.By using methyl alcohol to come purified product as the column chromatography of eluant, eluent.
In another embodiment, compound 1 is the AIE activity, because its Weak-luminescence in the PBS damping fluid, but after forming aggregation, send high light.Under the situation that does not have HSA, the solution of described compound in the PBS damping fluid is Weak-luminescence (Fig. 2) under 390nm.Yet, HSA added in the solution contain compound 1 can induce AIE compound strong luminescence under 475nm.HSA content is more high, and is luminous just more strong.Detect limit value and can be down to the low 1nM that reaches.In order to check the feasibility of protein analysis in body fluid, use artificial urine as the medium in the protein analysis.As shown in Figure 3A, compound 1 shows in artificial urine and similar photoluminescent property in the PBS damping fluid.Except having good sensitivity, compound 1 also shows the selectivity splendid to HSA, and other human protein and DNA are not shown remarkable reaction (Fig. 3 B), thereby accurate and reliable trace amount of protein analysis is provided.In addition, compound 2-4 has and compound 1 similar result, but their emission wavelength difference.
By in protein analysis, using the AIE fluorescent technique, design and made a kind of low cost, portable and technical simple multichannel urine albumen device.Fig. 4 is the process flow diagram that how can detect urine albumen about described device.The basic functional principle of protein analysis is to use water-soluble AIE shiner, thereby it can be urinated protein-interacting with target and produces by estimating or can detected fluorescence by instrument.In urine samples, exist under the situation of increased protein concentration, induce the luminous of AIE shiner by forming protein-shiner compound, in order to excite strong luminescence down at UV.Fluorescence signal not only can detect by photodetector, and be human eye as seen.For carrying out quantitative measurment, convert emissive porwer to voltage, if voltage surpasses predetermined starting voltage, just output element is unlocked so.The gained measured value can be used for measuring total urinary protein content.UV exposure, fluoroscopic examination and measurement are to carry out in the environment of light, so each element should be enclosed in the compartment of light, for example black box.
Fig. 5 shows the block diagram of the integrated circuit related with same in the urine Protein Detection device.Integrated circuit can be divided into four parts: (1) the Lights section 501; (2) sample and test section 502; (3) signal processing 503; (4) output 504.The opening and closing of the Lights section 501 control light sources (for example UV LED), described light source is used for the AIE shiner-target protein compound of excited sample container.The emission spectrum of UV LED has the narrow bandwidth of about 330-390nm, and peak value is 355nm, and the excitation wavelength of this narrow bandwidth and AIE shiner is fully mated, but can't detect (Fig. 6) by photodetector.In addition, the size of UV LED is little and in light weight, and this also is Consideration main in the manufacturing of mancarried device.Sample and test section 502 major control photodetectors, it is for detection of excite the fluorescence signal of launching from AIE shiner-target protein compound down at UV.The fluorescence that photodetector receives converts electric energy to from photon energy (photonic energy).Produce the signal of the most about 20mV from photodetector.Because signal is weak, and insensitive to detecting, therefore need to amplify this signal.Signal processing 503 comprises amplifier, and it amplifies several times with electric signal, and voltage comparator, and it is set threshold voltage and opens or closes output element with control.Voltage gain is defined as
And the electric signal scope through amplifying is that 0V is to 9V.Voltage comparator is configured to two input voltage value v of comparison
+And v
-, export 9V or 0V thus.Corresponding equation is:
When from the visible light intensity of AIE shiner-target protein compound emission when being enough to be detected by photodetector, amplifying signal makes voltage comparator become 9V, and, Open from This Side output element.When the visible light from AIE shiner-target protein compound emission was not enough to by force to the trigger voltage comparer, voltage comparator was 0V, and relevant output element can not be unlocked.Under any circumstance, no matter whether be subjected to the control of voltage comparator, still can access the quantitative output of voltmeter.Output 504 is connected with several output elements, these output elements can by in following three kinds of different output signal show samples urine albumen existence: i) LED, it provides light signal; Ii) hummer, it provides sound and iii) voltmeter, and it shows that numeral is to be used for quantitative measurment.It should be noted that any suitable output element all can merge in the described device in order to the target protein in the urine samples is carried out quantitatively.
Fig. 7 shows the outward appearance of urine Protein Detection device prototype.As can be seen, size is less than other conventional protein analysis system.In this embodiment, use plastic casing 701 to hold each element of urine Protein Detection device.Housing 701 also can be made by other material, but basic demand is can be every light and in light weight, so that device is easy to carry about with one.Sampling receptacle preferably is made of plastics and is disposable, pollutes to avoid producing in test.The solution that it is of a size of 1cm * 1cm * 5cm and can stores 5mL.Urine samples and prepositioned AIE solution are mixed in the sampling receptacle for analysis.Cell holder 702 is contained in the plastic casing 701.The function of cell holder 702 is positions of fixed sample container.The net weight of device can be less than 1.5kg.The ideal dimensions that is used for the device of portable use is about 162mm * 124mm * 80mm.Be equipped with UV LED 703 and have 330nm to the UV light of the narrow bandwidth of 390nm with emission, so as between detection period contained protein-shiner compound in the excited sample container.Photodetector 704 is placed on the housing 701 from the light path of protein-shiner compound emission under the exciting of the UV light that provides at UV LED 703, makes photodetector 704 can receive maximum emission intensity.In order to realize making the purpose of the pick-up unit that is easy to carry about with one, except the AC power pattern, can be battery 705 power supplies by direct current also.Battery 705 can be not rechargeable or rechargeable.When AC power was available, device switched to the Alternating Current Power Supply pattern.Signal amplifier 706 also is contained in the housing 701 with the voltage amplification that is used for converting from light signal by photodetector 704 to the level that can measure by output element or be amplified to the level that can open other output element when being scheduled to starting voltage when surpassing through the voltage that amplifies.Be equipped with voltmeter 707 to be used for measuring the voltage through amplifying from signal amplifier 706, in order to quantitative data is provided.Randomly, can be equipped with other output element for example hummer 707 and/or LED 708 in addition, with box lunch from signal amplifier 706 surpass the predetermined starting voltage in device, import through amplifying signal the time, provide qualitative output signal, for example sound or light.When hummer 707 and/or LED 708 are unlocked, it provides summary responses to the user, show that namely the detectable urine protein content in the urine samples of test is too high, study subject is unhealthy, and described reference sample contains the urine albumen for the reference content of setting predetermined starting voltage.In this embodiment, predetermined starting voltage is to use the reference sample that contains 30mg/L HSA to set.Yet starting voltage is adjusted according to the demand of user under the different situations easily.Though output element is provided in housing 701 outsides in this embodiment, described element also can be provided in enclosure interior.An advantage that is equipped with output element in outside is that output element can easily be dismantled and can be replaced by other suitable output element.
Carry out the performance test of device by the voltage that records under the different HSA concentration.Protein concentration is that the voltage difference between the potpourri of 0mg/L and the potpourri that protein concentration is 300mg/L is～200mV (Fig. 8).Change in voltage amplitude under the low-protein concentration is more obvious, and this helps to distinguish easily patient and healthy population.The starting voltage of device of the present invention can be adjusted as required, but the fundamental purpose of device being set starting voltage is, when the total urinary protein in the urine samples surpasses when reaching the certain concentration of starting voltage, healthy study subject and ill or suspicious study subject are distinguished.Can produce qualitative output signal in order to provide summary responses to the user who installs, thereby according to detectable urine protein content, determine the health status of the study subject in the test.
Since simple to operate and size is little, so described device can be widely used in family and clinic, in order to monitor health condition every day.
Embodiment
Synthesizing water-solubility AIE compound 1
In 250mL two neck round-bottomed flasks, 4-dihydroxy benaophenonel and 3 equivalent Zn powder are dissolved among the anhydrous THF of 80mL, the suspending liquid that forms is cooled to-78 ℃ under the N2 protection.Then with TiCl
4Dropwise add in the solution mixture.Wait to be warmed up to after the room temperature, make potpourri backflow 12h.With the reaction mixture cool to room temperature, filter then.After the filtrate evaporation, come the purifying crude product by recrystallization from THF/ methyl alcohol, to obtain white solid 1, two (the 4-hydroxy phenyls)-1 of 2-, 2-diphenylethlene.
At N
2Protection adds 0.5g (1.37mmol) 1 down in the 100mL round-bottomed flask, 2-two (4-hydroxy phenyl)-1,2-diphenylethlene and 20mL absolute ethyl alcohols.Stir the mixture and all dissolve up to all solids.(it becomes orange red after stirring 1h from colourless solution for 0.20g, the 3.0mmol) potpourri in 20mL ethanol dropwise to add NaOEt then.Add in the solution then and contain 0.35g 1, the 20mL ethanol of 3-propane sultone (2.88mmol).With potpourri vigorous stirring 12h, from solution, be settled out white product during this period.By filter collecting product, and with ethanol and acetone washed twice to obtain white solid.
Synthesizing water-solubility AIE compound 2
With two [4-(azido-methyl) phenyl]-1 of 1,2-, 2-diphenylethlene (1mmol), third-2-alkynes-1-sodium sulfonate (4mmol), copper sulphate (II) (0.2mmol) and the suspending liquid of sodium ascorbate (2mmol) be dissolved in the THF/H of 6mL
2In the O/ ethanol (1: 1: 1).Potpourri at room temperature stirred spend the night.Filter insoluble impurity and freeze-drying residual filtrate.By using methyl alcohol to come purified product as the column chromatography of eluant, eluent.
Synthesizing water-solubility AIE compound 3
At N
2Protection joins boron trifluoride dimethyl sulfide compound (50mmol) down and contains 2, in the DCM solution of two (4-methoxyphenyl) anti-maleic nitriles (1mmol) of 3-.Solution at room temperature stirred spend the night.After solution concentration, with ethyl acetate and rare HCl solution extraction crude product.Concentrate organic layer, crude product is transferred in the two neck round-bottomed flasks and is dissolved in be full of N
2Absolute ethyl alcohol in.Dropwise add the potpourri of NaOEt (3.0mmol) in ethanol then, it becomes orange red after stirring 1h from colourless solution.In solution, add 1,3-propane sultone (2.88mmol) then.With potpourri vigorous stirring 12h, from solution, be settled out white product during this period.By filter collecting product, and with ethanol and acetone washed twice to obtain white solid.
Synthesizing water-solubility AIE compound 4
With two (4-(azido-methyl) phenyl)-1 of 2,5-, the copper sulphate (II) that 1-dimethyl-3,4-diphenyl-thiophene are coughed up (1mmol), third-2-alkynes-1-sodium sulfonate (4mmol), sodium ascorbate (2mmol) and catalytic amount is dissolved in THF/H
2In the O/ ethanol (1: 1: 1), the solution that forms at room temperature stirred spend the night.Filter insoluble impurity and freeze-drying residual filtrate.By using methyl alcohol to come purified product as the column chromatography of eluant, eluent.
Prepare artificial urine
The prescription that provides according to Brooks and Keevil prepares artificial urine.The potpourri of following material is dissolved in the Millipore water of 1000mL: lactic acid (1.1mM, 0.096mL), citric acid (2.0mM, 0.42g), sodium bicarbonate (2.5mM, 0.21g), urea (170mM, 10.21g), lime chloride (2.5mM, 0.278g), sodium chloride (90mM, 5.26g), magnesium sulphate (2.0mM, 0.24g), sodium sulphate (10mM, 1.42g), potassium dihydrogen phosphate (7.0mM, 0.95g), dipotassium hydrogen phosphate (7.0mM, 1.22g) and ammonium chloride (25mM, 1.34g).By adding 1.0M hydrochloric acid the pH value of solution is adjusted to 6.00.Then aqueous solution is sterilized in pressure cooker.
Protein analysis
In disposable plastic container, the 1.5mL analytic sample is mixed with prepositioned compound 1 solution of 1.5mL (1 μ M).Container is put into pan straddle, and open the UV led light source.Convert electric signal from the fluorescence of protein-shiner compound emission to by photodetector, the value of the voltage of generation is transformed into the numeral that is shown by voltmeter.
In case of necessity, difference in functionality discussed in this article can different order be carried out, and/or carries out simultaneously each other.In addition, in case of necessity, one or more above-mentioned functions can be chosen use wantonly, or use capable of being combined.
Though various aspects of the present invention are illustrated in independent claims, but other side of the present invention comprises other combination of the feature of the feature of described embodiment and/or appended claims and independent claims, and is not only the combination of clearly illustrating in the claim.
Though it shall yet further be noted that and above described exemplary of the present invention, these are described content and should not be considered as restrictive.On the contrary, under the situation that does not depart from the scope of the present invention that appended claims limits, can carry out some variations and modification.
Claims (21)
1. portable urine Protein Detection device, it uses the total urinary protein in water miscible aggregation inducing photism shiner detection and the quantitative urine samples, described device comprises housing, light source, sampling receptacle, cell holder, photodetector, signal amplifier, a plurality of output element and the integrated circuit related with same every light
Wherein said light source, described cell holder, described photodetector, described signal amplifier and integrated circuit related with same are closed in the described housing so that isolated with exterior light between described detection period;
Described light source is led light source, and it can produce the light with narrow bandwidth, the excitation wavelength coupling of the light of described narrow bandwidth and described water miscible aggregation inducing photism shiner, and be positioned at outside the emission spectrum of described aggregation inducing photism shiner;
Described sampling receptacle is configured for the potpourri that holds described water miscible aggregation inducing photism shiner and described urine samples, and emitting fluorescence when being exposed to described light source;
Described cell holder is configured for the position of fixing described sampling receptacle;
Described photodetector is configured for and detects fluorescence signal and convert described fluorescence signal to electric signal, and described fluorescence signal is to be launched being exposed under the situation of described light source by the described water miscible aggregation inducing photism shiner in the described sampling receptacle and described urine samples; With
Described signal amplifier is configured for electric signal is amplified to 0-9V;
Described voltage comparator is configured to set threshold voltage, be used for comparing with the electric signal that amplifies by described signal amplifier, whether be unlocked with definite described output element, and/or whether the value of the electric signal of described amplification can be measured quantitatively by described output element; With
Described output element is configured to the level of urine albumen in qualitative and/or the quantitative response sample.
2. device according to claim 1, wherein said water miscible aggregation inducing photism shiner comprises the skeleton of following any chemical formula:
R wherein
1Combined thing (X) independently
nS0
3 -Na
+Replace, and wherein X is selected from alkyl, unsaturated alkyl, assorted alkyl, naphthenic base, Heterocyclylalkyl, aryl or heteroaryl, and n=0 to 20 wherein.
3. device according to claim 2, wherein said water miscible aggregation inducing photism shiner can with described target urine protein-interacting, in order to produce by the detectable fluorescent emission of instrument and visible color.
4. device according to claim 2, wherein said water miscible aggregation inducing photism shiner comprises following any chemical formula:
5. device according to claim 4, wherein said water miscible aggregation inducing photism shiner has specificity to human serum albumins.
6. device according to claim 1, wherein said light source is the UV led light source, the UV light of its generation have 330nm to 390nm bandwidth and its peak value about 350nm, the excitation wavelength coupling of this and described water miscible aggregation inducing photism shiner.
7. device according to claim 3, wherein when described water miscible aggregation inducing photism shiner had been exposed under the described light source with described urine protein-interacting, described water miscible aggregation inducing photism shiner had maximum emission intensity under about 475nm.
8. device according to claim 1, wherein said sampling receptacle is of a size of 1cm * 1cm * 5cm and maximum volume is about 5mL.
9. device according to claim 1, wherein said sampling receptacle is made of plastics and is disposable.
10. device according to claim 1, wherein said integrated circuit related with same comprise for the Lights section of the opening and closing of the described light source of control, be used for receiving from the fluorescence signal of described photodetector and with described fluorescence signal and convert sample and the test section of electric signal, the output that is used for the signal processing of the described signal amplifier of control and is used for receiving voltage and opens described output element to.
11. device according to claim 1, wherein said output element comprises one or more light-emitting devices, sound-producing device and voltmeter.
12. device according to claim 1, it is of a size of about 162mm * 124mm * 80mm.
13. device according to claim 1, its net weight is less than 1.5kg.
14. device according to claim 1, wherein said water miscible aggregation inducing photism shiner is 0-300mg/L for the working range of described urine albumen.
15. device according to claim 1, wherein said water miscible aggregation inducing photism shiner is about 5mg/L for the detectability of described urine albumen.
16. device according to claim 4, wherein when the human serum albumins in described water miscible aggregation inducing photism shiner and the described urine samples interacts, described water miscible aggregation inducing photism shiner can be launched the maximum fluorescence signal under about 475nm, and has the detectability of about 1nM.
17. a method that is used for measuring based on water miscible aggregation inducing photism shiner the urine samples total urinary protein, it comprises:
Preparation contains the solution of described water miscible aggregation inducing photism shiner;
Described solution is placed in the sampling receptacle in advance, and described sampling receptacle is installed on the cell holder;
Described urine samples is injected the described sampling receptacle that is placed with described solution in advance;
The described sampling receptacle that will hold the potpourri of described solution and described urine samples is exposed to the UV light of the about 355nm that is produced by light source;
Detection is from the fluorescence signal of about 475nm of the potpourri emission of described solution and described urine samples;
Described fluorescence signal is converted to electric signal and described electric signal is zoomed into detectable voltage;
Measure described voltage, and described voltage and predetermined voltage from reference sample record with variable concentrations target protein are compared, in order to measure the content of target protein described in the described urine samples; With
Content based on target protein described in the described urine samples is measured described total urinary protein.
18. method according to claim 17, wherein when described voltage surpassed starting voltage, described voltage was opened other output unit in addition to produce output signal.
19. method according to claim 18, wherein said output signal are selected from luminous or sound or perceived any signal.
20. method according to claim 17, wherein to be placed into described detection in advance be to carry out every the environment of light or compartment from described.
21. method according to claim 17, wherein said water miscible aggregation inducing photism shiner comprises following any chemical formula:
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| US13/727,558 US20130177991A1 (en) | 2012-01-09 | 2012-12-26 | Aggregation induced emission luminogen-based urinary protein detection device for monitoring human health |
| US13/727,558 | 2012-12-26 |
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