CN101426448A - Methods and kits for early stage caries detection - Google Patents
Methods and kits for early stage caries detection Download PDFInfo
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Abstract
Methods and kits are provided for identifying very early stage carious lesions using a detectable probe that binds to the lesion.
Description
Related application
The application with respectively on April 18th, 2006, on July 7th, 2006, on October 11st, 2006, on February 15th, 2007, the sequence number to United States Patent (USP) and trademark office's submission was 60/792,768,60/819,135,60/850,922 and 60/901,421 provisional application is relevant, and the full content of these provisional application is all incorporated this paper into by quoting as proof.
Technical field
Here, the present invention relates to stage use in early days can preferably detect dental caries in conjunction with the compositions of dental caries method, preceding pathological changes dental caries zone can be detected by the light absorption near infrared wavelength region, perhaps use the hand-held detector luminous detection of spectrophotometer or other Optical devices, perhaps adopt the uviol lamp fluorescence radiation to detect, or detect by the circular dichroism fluorescence radiation.
Background technology
Although mainly the preventive measure that reduces dental caries by the applicable in various ways fluoride has obtained good effect, yet dental caries and periodontal remain the main cause of whole world loss of tooth.If detected in early days, for example the demineralization of dental surface does not develop into dentin as yet, and early stage dental caries pathological changes can be cured by remineralization.
Yet if pathological changes has developed into dentin, amalgam or other synthetic dental fillings are for example placed in the measure of reparation property, and just becoming must.In general the measure of this class reparation property has more invasive, and the while is for the patient or provide the third party of medical expense also to mean more expensive expense.Therefore, the early detection of dental caries pathological changes is very crucial part in prevention and treatment dental caries.
In 20 th Century, index and the method for measuring the dental disorder degree grow up.The sick research of modern popular starts from the 1950's, and many reliable researchs are also carried out after nineteen sixty.ORCA is one of science corporations that are devoted to the earliest diagnosis dental caries in the low crowd of tooth lesion growth probability.ORCA dental caries diagnostic work group is pointed out in the summary seminar: " being used for determining that the dental caries pathological changes is the development of method stable or that worsen, is top-priority problem in the dental caries research ".
Tradition dental caries detection method relatively poor diagnosis performance impels research worker outside the x-ray technology of standard at present, the development quantitative detecting method, and for example electric conductance detects, the light color method that looses, MAK BY LASER EXCITED FLUORESCENCE.Develop these methods and have three motivations at least: (1) quantitative detecting method may detect pathological changes at commitment more compared with traditional method; (2) quantitative detecting method is more reliable compared with qualitative checking method; (3) quantitative detecting method can be with the process to the harmless mode monitoring of diseases of patient.
Yet, in calendar year 2001 U.S.'s sound development association about the systematic review of " diagnosis and treatment dental caries---in life whole " diagnostic method of preparing, fail to confirm the relative curative effect of the whole bag of tricks of current detection dental caries.
Summary of the invention
On the one hand, the invention provides a kind of method of the patient's of detection early stage caries, this method comprises: the optical detection probe optionally is combined on the early stage caries, utilizes Optical devices to detect to be combined with the dental caries of probe.In certain embodiments, early stage caries is meant the stage before demineralization, and promptly these dental caries are " white maculas " or just send out and/or early stage caries.
In some embodiment of the method, selective binding detects and also comprises fluorescent probe contact tooth, fluorescent probe is selected from the group of following formation: tetracycline, HylightFluor, Qdot, Fox Green, amycin, riboflavin, chlorophyll, porphyrin, illumination of teeth under excitation wavelength comprises in the embodiment of this method by detecting emission wavelength light emission within the specific limits and diagnosing.
In the another embodiment of the method, detect optionally in conjunction with comprising that also probe is a chemiluminescent substance, for example luminol and fluorescein the step of probe contact tooth.The method comprises that also tooth contacts other reactants as hydrogen peroxide, luciferase and metal ion as catalyst, with the luminous detection in the certain limit as diagnosis.
In the another embodiment of the method, selective binding detects and comprises that also the absorption that detects near infrared light (NIR) in the certain limit is as diagnosis gold colloidal contact tooth.In the another embodiment of the method, selective binding detects and also to comprise the probe of quantum dot compounds contact tooth, detect luminous or the fluorescence dichromatic as diagnosis.In the another embodiment of the method, selective binding detects and also comprises the probe of conjugation quantum dot compounds contact tooth, this conjugate is attached on second dose, is selected from the group of following formation: tetracycline, bismuth, gold colloidal or analog, detect fluorescence radiation or fluorescence dichromatic then.In the another embodiment of the method, selective binding detects and also comprises gold colloidal contact tooth, uses HiLyte Fluor 750 hydrazide (a kind of novel fluorescent dye) to detect fluorescence radiation as diagnosis.
In the another embodiment of the method, make the optical detection probe charged, probe is connected on the early stage caries by electrovalent bond.In the another embodiment of the method, detect dental caries by photometry.In another embodiment, probe is a tetracycline, and selective binding tetracycline probe is observed white macula and detected dental caries.In yet another embodiment, selective binding quantum dot probe is observed translucent fluorescence speckle and is detected dental caries.In yet another embodiment, the bottom of 50-100 μ m diagnosis white macula detects dental caries on adamantine surface or under the surface.
In another embodiment of the method, fluorescent probe is a tetracycline, and the wavelength that is radiated on the tooth is about 350-450nm, and the wavelength that detects fluorescence is about 450-600nm.In another embodiment, fluorescent probe is Hilyte Fluor, and the wavelength that is radiated on the tooth is about 720-750nm, and the wavelength that detects fluorescence is about 750-800nm.In another embodiment, fluorescent probe is Qdot, and the wavelength that is radiated on the tooth is about 400-750nm, and the wavelength that detects fluorescence is about 750-900nm.In another related embodiment, fluorescent probe is a Fox Green, and the wavelength that is radiated on the tooth is about 750-800nm, and the wavelength that detects fluorescence is about 820-870nm.In another embodiment, fluorescent probe is an amycin, and the wavelength that is radiated on the tooth is about 400-500nm, and the wavelength that detects fluorescence is about 600-700nm.In another embodiment, fluorescent probe is a riboflavin, and the wavelength that is radiated on the tooth is about 400-500nm, and the wavelength that detects fluorescence is about 500-700nm.In another embodiment, fluorescent probe is a chlorophyll A, and the wavelength that is radiated on the tooth is about 600-650nm, and the wavelength that detects fluorescence is about 670-900nm.In another embodiment, fluorescent probe is a porphyrin, and the wavelength that is radiated on the tooth is about 550-650nm, and the wavelength that detects fluorescence is about 650-750nm.
In another embodiment of the method, probe comprises luciferase, fluorescein and ATP, and the luminous wavelength of detection of biological is about 600-800nm, and in another related embodiment, probe is a gold colloidal, and the wavelength that detects absorbance is about 500-800nm.In another related embodiment, probe is a bismuth, and the wavelength that detects absorbance is about 500-800nm.
In some embodiments, these dental caries are interproximal caries.In another embodiment, before contact, the proximal surface zone can enter by at least a method that is selected from down in the group: insert an escapement, wrap up probe with metal or plastic tape when probe is inserted the proximal surface zone.
In some embodiments of the method, probe is conjugate or HiLyte Fluor 750 hydrazide (a kind of novel fluorescence dyestuff) that contain the quantum dot compositions.In another embodiment, probe is the gold colloidal that comprises nanogold particle.In another embodiment, probe is the Tetracyclines fluorescent probe, contains chlortetracycline at least, oxytetracycline, a kind of in the doxycycline.
In some embodiments, be at least about 20 seconds, 40 seconds or 60 seconds the time of contact of Chi Xuing.In other embodiments, Lycoperdon polymorphum Vitt, silver color, white or translucent speckle are the signs of dental caries position.In another related embodiment, the area size of Lycoperdon polymorphum Vitt, silver color, white or translucent speckle is the sign of dental caries lesion degree.
In some embodiments, the dental caries that is combined with probe detects by Optical devices in the use hand held oral.In another embodiment, use the hand held oral internal probe on uviol lamp or the spectrophotometer/Optical devices to detect luminous.
In another embodiment, this method also relates to before contact, detects automatic fluorescence earlier.In yet another embodiment, this method further relates to the dental caries of solidifying detection by remineralization.In some embodiments, dental caries detect to as if mammal.In other embodiments, detection to as if the people.
In some embodiments, this method also relates to the image picture that preparation is combined with the dental caries zone of probe.In other embodiments, this method further comprises the remineralization dental caries, in this process, and monitoring dental caries pathological changes, and prevent and reduce pathological changes.
On the other hand, the invention provides a kind of test kit and be used to detect patient's commitment dental caries, described test kit comprises the detector probe that can be combined on the dental caries, and described test kit also comprises a kind of container, and the positive control tooth sample in early lesion stage.In another embodiment, the invention provides a kind of test kit and be used to detect patient's commitment dental caries, described test kit comprises at least a probe that is selected from down in the group: gold colloidal; Fluorescent probe; Bioluminescence; These probes optionally are combined on the dental caries, and this test kit also comprises a kind of container, and the positive control tooth sample in early lesion stage.
In some embodiments, described test kit also comprises the operation instructions that use with Optical devices.In another embodiment, the fluorescent probe in the test kit is the conjugate of tetracycline or tetracycline.For example, fluorescent probe is selected from the group of following formation: Fox Green, amycin, riboflavin, chlorophyll, porphyrin.
On the other hand, the invention provides a kind of test kit and be used to detect patient's commitment dental caries, described test kit comprises detector probe, Optical devices and container.In a kind of relevant embodiment, described test kit also comprises the positive control tooth sample in early lesion stage.In another related embodiment, this test kit also comprises operation instructions.
In another related embodiment, described Optical devices are selected from down at least one in the group: light wave checkout gear, photographing unit and fiber optic devices in the hand held oral.In some embodiments, this optical detection apparatus also comprises an electromagnetic wave transmitter, and the electromagnetic wave that is used to produce specific wavelength comes the fluorescence excitation probe.
In some embodiments, have at least a kind of compositions to be selected from fluorescent composition or bioluminescence compositions in the probe in the test kit.In an embodiment of being correlated with, probe is a chemical luminous composite, for example: luciferase, fluorescein and their mixture.In another relevant embodiment, probe is a fluorescent probe, for example: Fox Green, amycin, riboflavin, chlorophyll, porphyrin.And in another related embodiment, probe contains the group that a kind of compositions is selected from following formation: Qdot, gold colloidal and bismuth at least.
In some embodiments, probe is a unit dose.In another embodiment, test kit also comprises the applicator of probe, and as aerosol apparatus, bite wing can be extruded colloidal compressed pipe.
Description of drawings
Fig. 1 is the sketch map of one group of degree of depth (from enamel surface to half enamel thickness) " white macula " in 100 μ m.This early stage caries can not detect with conventional means, just can detect because the X-ray detection needs focus to reach darker degree (400-500 μ m).
Fig. 2 is the photo that is used to detect the Optical devices that are combined in the probe on the early stage caries in one group of a plurality of in the present invention embodiment.Photo shows: light source (1) illuminates a tooth, observes the early stage caries pathological changes that combines probe.Photographing unit (2) is used herein to the picture of catching the tooth that the early stage caries pathological changes is arranged that combines detector probe.Computer (3) control luminous source and storage detect data.Platform (4) is used for fixing sample, such as the synthetic tooth that the early stage caries pathological changes is arranged that needs illumination, Dens Bovis seu Bubali or enamel section.Optical fiber (5) transmission and focusing are from the electromagnetism light wave of light source (1) emission, the tooth regions of electromagnetism light-wave irradiation on platform (4).
Fig. 3 is the light absorption photo on the synthetic tooth of an early stage caries pathological changes that is combined with the bismuth probe.
Fig. 4 is the fluorescence photo on the synthetic tooth of an early stage caries pathological changes that is combined with the amycin probe.
Fig. 5 is the fluorescence photo on the synthetic tooth of an early stage caries pathological changes that is combined with the riboflavin probe.
Fig. 6 is the fluorescence photo on the synthetic tooth of an early stage caries pathological changes that is combined with the chlorophyll A probe.
Fig. 7 is the fluorescence photo on the synthetic tooth of an early stage caries pathological changes that is combined with the porphyrin probe.
Fig. 8 is the bioluminescence photo on the synthetic tooth of an early stage caries pathological changes that is combined with luciferase and fluorescein probe.
The specific embodiment
The probability of dental caries detection by quantitative depends on the level of development of Optical devices in the current oral cavity.Yet the dental caries examination criteria that current industry is generally acknowledged is clinical and radiographic test combines, and Optical devices can detect the change of the very small optical property that may be ignored by human eye in the oral cavity.Such development also can make the patient exempt under the radiation when being exposed to the radioactivity image check, the labour-intensive Clinical detection time in the time of can reducing very early stage dental caries and check, even can make and may need originally to wait until that the detection that next stage could detected dental caries becomes possibility.
The demineralization of tooth enamel surface is the result of acid and antibacterial existence in the oral cavity, and these factors cause dental caries.Therefore, molecule can with just/to be combined in commitment dental caries zone be the demineralization zone to the form of anion, can not limit the use of the potential probes in the method and apparatus among the present invention.
Various types of other useful probe has other extra characteristics for light wave among the embodiment.The probe that has utilizes excitation light wave that fluorescence is provided; What the probe that has did not have a light requirement excites generation fluorescence, and promptly bioluminescent probe is such as the luciferase/luciferin system; The probe that has absorbs illumination light such as bismuth, gold colloidal.
Distinguish dental caries at this nuance of seeking the optical property (reflectivity curve pattern, color data, scattered/absorbed coefficient, perhaps other optical datas) of at least one standard, do contrast with a sound tooth structure.Hand-held device can sequencing, can be designed to obtain the correct optical characteristics of dental caries in the patient oral cavity.Surprisingly, a series of probes of describing in the Application Example have in fact detected these differences in experiment.Therefore, the use Optical devices detect the potential variation in early stage caries (as be combined with the energy fluorescence radiation or use other agents probe of the fluorescence radiation automatically) pathological changes, with this instrument as the detection early stage caries.
Optimize irradiation (exciting) wavelength of each probe and the emission of fluorescence.The Optical devices of standard can be revised to obtain only use.Illumination light is used to shine whole dental surface, for example, uses illuminating bundle scanning dental surface.Scanning is extremely important for the detection in proximal surface zone.Further embodiment shows that lighting angle is also very important, and like this, the detection of probe was effective especially when direction of illumination was parallel with the enamel fiber direction.
Because Optical devices have used various probes in the present invention, use camera (as a small-sized fiber optic camera) can obtain the optimum detection result.The additional standard relevant with Optical devices has: the diameter of the light beam of direct irradiation tooth, (less relatively light beam can obtain better data); Be used to detect the diameter (diameter is the smaller the better, and that considers when using endoscope is similar) of the photographing unit of absorbing light probe; Be used to detect the diameter (diameter is the smaller the better, and endoscope is similar to using) of the photographing unit of fluorescence radiation probe; And the ability of the light beam that scans of intensity of illumination that can scan and photograph function record.
What in addition, recently many relevant dental caries detected studies show that do not have accurate optical means to detect the interproximal caries pathological changes.Though based on " near-infrared " detection (NIR) is a kind of technology that can catch interproximal caries pathological changes image, false positive rate is very high, and therefore this method can not be applied to the clinic far away.Yet, surprisingly, in an embodiment, find that some compositions can be combined on the dental caries specifically, and can be detected by Optical devices.
Term " white macula " referred to herein as very early stage from enamel inside the rotting of (100-150 μ m with interior or more near enamel surface) beginning.In Fig. 1, the space (space between the enamel fiber is 10 μ m) of enamel fiber is invaded in antibacterial and acid, produces demineralisation here, arrives enamel surface then.The white macula of imagination detection herein is in the pathological changes commitment, and method and the technology of using detection herein to provide make the method for remineralization become possibility.These treatments will be a major contribution to improving dental health and reduction expense.
The word " probe " that uses in the present invention refers to can be special or preferentially be combined in detectable compositions on the dental caries.Comprising coloring agent, label with can be incorporated into dye liquor on the dental caries adamantine layer.In some embodiments, probe is a fluorescent composition, for example: tetracycline, Hylight Fluor, Qdot, Fox Green, amycin, riboflavin, chlorophyll, porphyrin.Usually, by detect the light wave emission of certain limit at the excitation wavelength illumination of teeth with under emission wavelength, detect the fluorescent composition that is attached on the dental caries.In one embodiment, probe is a chemical luminous composite, as: luciferase and fluorescein or photoprotein.
In one embodiment, probe is the light-absorbing compositions of a kind of energy, as bismuth, or gold colloidal.Usually, by the specific zone of illumination, if any the tooth of dental caries pathological changes, and the light of the absorption specific wavelength of detection tooth one regional extent, as, absorb near infrared light (NIR) and detect light absorbent composition.
In people's such as Gobin article Lasers in Surgery and Medicine 37:123-129 (2005), golden nanometer particle is designed to a kind of material that NIR is had strong absorption, golden nanometer particle is applied near infrared spectrum welded seam is provided in researching wound healing, is called as laser-biological tissue's welding and laser-biological tissue's scolding tin in rat skin wound healing pattern.Mazzola, L has described the various functions of golden nanometer particle in Nature Biotechnology (21 (10): 1137-1143,2003), comprise the test of molecule detecting property, location payload transmission, photoactivation with separate the ablation of tissue that the making of grade life is sent out.
People such as Gobin go back tetraethyl orthosilicate in the experiment of synthetic gold nano ball, then nano-silicon core and 3-aminopropyl triethoxysilane (APTES, Sigma-Aldrich, St.Louis, MO) reaction, the amido energy deposited gold colloid on the silicon wicking surface.Gold grain (the Auroshell that can on market, buy
TM) be Nanospectra Biosciences company (Houston, TX) and Purest Colloids company (
Westampton NJ) produces.What use among the embodiment of this paper is that (BioRad, Hercules CA), yet it is contemplated that any commercial gold colloidal all plays a part similar to gold colloidal total protein probe in to the detection of early stage caries.
Tetracycline except as it for our the known antibiotic, still fluorescence propellant in a kind of photometering is as labelling skeleton development/formation.But tetracycline makes tooth discoloration, is referred to as dentist circle " tetracycline pigmentation teeth ".Tetracycline is attached on the surface of newly-generated skeleton or tooth, and bonded result can observe and is phosphor dot or photoluminescence line." tetracycline fluorescence " is as being attached to newly-generated skeleton or the agent on the tooth, when the irradiate light of scheduled wavelength, can send fluorescence, its include, but is not limited to the member of all tetracycline families and other compositionss such as gold compound, quantum dot compounds, HiLyte fluor 750 hydrazide chemical compounds and other any have can be incorporated on newly-generated skeleton or the tooth and under excitation wavelength irradiation, send fluorescence or this functional attributes of other optics/physical signallings chemical compound.
Fox Green (ICG) is a kind of tricarbocyanine, after exciting, can be at about 800nm, and about 820nm, about 840nm or about 860nm place are luminous.ICG is commercialization, and can (Jupiter FL) buys, and has been used for infrared photography, and the preparation thunder is stepped on optical filter, and the diagnosis used of blood volume determination, cardiac output or liver function is auxiliary from H.W.Sands company.The character of ICG has detailed description in people's such as Landsman article (J.Appl.Physiol., 40:575-583,1976).
Amycin (being also referred to as Hydroxydaunomycin) is a kind of DNA cancer therapy drug, is widely used in chemotherapy.The chemotherapeutics weight range of amycin is 60-75mg/m
2Amycin is at certain wavelength (550nm, about 600nm, about 650nm) according to appointment fluorescence radiation, and this characteristic has been applied to the active measurement of RESEARCH ON CELL-BIOLOGY medicine efflux pump and various different types of multidrug resistant albumen in intracellular location.The concentration of using is far below chemotherapy dosage.Amycin is commercialization, and can (St.Louis MO) buys from Sigma-Aldrich company.
Riboflavin (vitamin B2) is a kind of micronutrient of easy absorption, plays a role in various cell processes, as the energy metabolism.Riboflavin is a kind of easy absorption, and water miscible micronutrient provides energy to assist fat, carbohydrate, proteinic metabolism.The generation of erythrocytic formation and breathing, antibody and mediator's bulk-growth and breeding also need the participation of riboflavin.Riboflavin can be used as the intravital particulates emission that is called free radical of antioxidant for clearing machine.Riboflavin is to the health of skin, fingernail, hair growth, and good health status comprises that to regulate thyroid function all extremely important.
Because riboflavin is water miscible, excessive riboflavin can not store, and generally discharges from urine.Generally speaking, the toxic dose known to riboflavin does not have.Every day, minimum recommended measures range 1mg-2mg was as meal supplement, was 50mg-100mg and typically treat the daily dose scope, in fact, was attached to the needed riboflavin of dental surface in the method and wanted much less.Riboflavin is commercialization, and can from Sigma-Aldrich company (St.Louis MO) buys, it certain wavelength (as 450nm, 550nm, 650nm, 750nm) fluorescence radiation down.The character of riboflavin has detailed description in people's such as Du article (Photochemistry and Photobiology, 68:141-142,1998).
Chlorophyll A is a kind of photosynthetic pigments of green, and at the about 600nm of wavelength, about 700nm or about 800nm place can be luminous.Chlorophyll A is commercialization, and can (St.Louis, MO) (Sunnyvale CA) buys with Turner Designs company from SigmaChemical company.Because chlorophyll is the part in the human normal diet, it does not have known toxicity.
Porphyrin is a kind of big heterocycle, by 4 pyrroles time group with 4 methyl bridges (=CH-) para-position is formed by connecting.The a large amount of conjugated structure of porphyrin makes this chemical compound present color, that is to say, can be at about 600nm, and 650nm, 700nm wavelength place fluorescence radiation.Porphyrin is commercialization, and can (St.Louis MO) buys from Sigma-Aldrich company.Porphyrin is relevant with hemoglobin and Myoglobin, and they are that the component of the basic food of animal also is the part in the human normal diet, so it does not have known toxicity yet.
For bioluminescent probe, excitation energy is obtained by chemical reaction, rather than derives from light source.Fluorescein and luciferase are the examples of a substrate and relevant enzyme, the reaction that catalysis fluorescence produces, i.e. and bioluminescence, adenosine triphosphate (ATP) has participated in reaction.Under the situation that ATP exists, luciferase luminous (for example, the about 500nm of wavelength, about 550nm, about 650nm) when an amount of fluorescein substrate contacts, the photon of emission is detected by a photosensitive device (Optical devices as mentioned in this article).Fluorescein and luciferase are extensive use of, as the stage that is used for observing bioprocess and infection.The commercialization of fluorescein and luciferase, and can (St.Louis MO) buys from Sigma-Aldrich company.
The other example of bioluminescence compositions has green fluorescent protein (GFP) and aequorin.These bioluminescence compositionss are separated from Jellyfish.When calcium ion in conjunction with aequorin, complex resolves into the apoenzyme aequorin and can send the light emitting composition of blue light at about 466nm wavelength.The commercialization of synthetic aequorin, by name
Commodity can be from Sealite, (Bogart Ga.) buys in Sciences company.GFP is luminous in the lower green glow part (about 490nm-570nm) of visible spectrum.Synthetic GFP commercialization can (Mountain View, CA) company buys from Clontech company.
Be called the solution composition of the compositions of " quantum dot " by a kind of nanoscale (about protein size) cluster.Illustrative
Be that (Carlsbad CA) buys from Invitrogen company.This bunch comprises various raw material combination, as alkali metal (Li, Na, K, Rd, Cs and Fr), alkaline-earth metal (Be, Mg, Ca, Sr, Ba and Ra), transition metal (Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Y, Zr, Nb, Mo, Tc, Ru, Rh, Pd, Ag, Cd, Hf, Ta, W, Re, Os, Ir, Pt, Au and Hg), lanthanides (La, Ce, Pr, Nd, Pm, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb and Lu) and radioelement (Ac, Th, Pa, U, Np, Pu, Am, Cm, Bk, Cf, Es, Fm, Md, No and Lr) be the combination of core with silicon or silica gel.
The quantum dot preparation is used as fluorescent agent, is attached on the sample, uses irradiation under ultraviolet ray then.The quantum dot preparation shows big molar extinction coefficient, high light resistance and the adjustable emission of strong granularity.The adjustable aspect of emission peak is because commercial preparation comprises different metal mixture and different size particles, can regulate infrared, far infrared or HONGGUANG and shine the quantum dot that is attached on the dental caries.In addition, the quantum dot granular preparation can be determined whole positively charged or electronegative according to the different metal of combination.
Show that herein because the reason of electric charge, the quantum dot preparation optionally is attached on the enamel of decalcification, and the neutral enamel of health is not had influence.
In addition, quantum dot can be in conjunction with described any microminiaturization compound, and as tetracycline, (a kind of fluorescent dye is used for labelling complete cell and active somatic cell to calcein; U.S. hero Life Technologies, Inc.) and derivant, these materials have affinity interaction to the decalcification enamel.These are in conjunction with forming " the affine quantum dot of enamel " preparation.Use the affine quantum dot of these enamels, dens translucens enamel fluorescence radiation can detect the decalcification enamel.Perhaps, the quantum dot that is attached on the decalcification enamel also can pass through dichromatic (as fluorescence-detected circular dichroism) check.
A kind of very practical compositions of current application is HiLyte Fluor 750hydrazide (a kind of novel fluorescence dyestuff), and this is a kind of commodity fluorescent dye that is used for colloidal gold probe.(AnaSpec company, San Jose, California).HiLyteFluor 750 hydrazide are a kind of carbonyl reaction fluorescent marker dyes.It can be used to the labelling glycoprotein, as horseradish peroxidase (HRP).HiLyte Fluor 750 hydrazide have long wavelength in existing carbonyl reaction HiLyte Fluor dyestuff, its fluorescent emission wavelength is about 782nm, with far infrared fluorescent dye such as HiLyte Fluor 647 commonly used, HiLyte680, reach allophycocyann (APC) and well distinguish, be beneficial to the polychrome analysis.
The dosage of probe depends on mammiferous kind, body weight, age and individual instances, individual drugs dynamics data, and administering mode.The probe here is fit to contact or is applied on the tooth of mammal (people and superior being), is used for detecting the early stage caries pathological changes that is combined with this probe, comprises various probes or salt pharmaceutically acceptable, that help detecting in the present method.Probe in this method is applicable to oral cavity contact or is applied to mammiferous tooth (people and higher mammal), comprises the effective dose of probe, separately or together with a large amount of pharmaceutically acceptable carrier or buffer.
The concentration of this method middle probe solution or its touch the concentration of the pharmaceutically acceptable salt of dental surface, as the adult tooth surface, from about 1ng/ml to about 100ng/ml, from about 100ng/ml to about 500ng/ml, from about 500ng/ml to about 1 μ g/ml, from about 1 μ g/ml to about 50 μ g/ml, from about 50 μ g/ml to about 500 μ g/ml.Child's dentistry estimates that dosage can significantly reduce the dosage as 1/2nd to 1/10th.
The long-term needs of dental medicine are the detections of early stage caries.Before also these compositionss were not used as the probe that detects dental caries, as in the initial period of following symptoms such as early stage demineralization.Another long-term needs are detections of proximal surface pathological changes, the proximal surface pathological changes promptly is positioned at the pathological changes on two interdental surfaces, still do not have at present and may realize by the mode of X-ray (stinging fin) or clinical visual examination early stage proximal surface pathological changes promptly is positioned at the detection of the pathological changes of enamel 1/2nd depth boundses.
Be applicable to that Optical devices that detection is combined with the dental caries of probe according to this method comprise some and the similar optical module of endoscope.These assemblies comprise the rigidity or the softish pipe that contain one or more fibre systems, the passage of Guan Youyi machinery, as be used for illuminating the light conveying system on the target tooth surface under the monitoring.In some embodiments, these Optical devices also comprise the device of a launching electromagnetic wave.This device has a detailed description in people's such as Bukosky article (United States Patent (USP) the 6th, 076, No. 948, on June 20th, 2000 published).
In one embodiment, light conveying system comprises the light source that is positioned at the outside, oral cavity, and light passes through the fibre system direct projection to tooth.Perhaps, Optical devices comprise built-in light source, as light emitting diode.In some embodiments, Optical devices comprise lens combination, and image is transferred to user.User can be controlled the wavelength of transmitting illuminant, as, the emission suitable wavelengths is come the fluorescence excitation probe.The example of light wave checkout gear is the ZE-411 type stomatology endoscope (quick numeral science and technology company limited, Guangdong, the China of looking in Guangzhou) of SharpVision company in the hand held oral.
In some embodiments, Optical devices are uviol lamps.Ultraviolet is meant that wave-length coverage is the electromagnetic wave of 10nm to 400nm.Wave-length coverage is that the ultraviolet of 345nm-400nm produces a kind of " black light " effect, and promptly the wavelength in this scope makes some compositions send fluorescence.Commercial uviol lamp can be buied from Unilam company (Korea S).
In some embodiments, Optical devices are spectrophotometers.At this, spectrophotometer is used for measuring light intensity, and promptly this device energy measurement light intensity is as the function of color (or in particular, i.e. light wavelength), in some embodiments, spectrophotometer is used for detecting the fluorescent probe on the tooth that is combined in the early stage caries pathological changes.It is commercial that spectrophotometer can (San Jose CA) buys from Hitachi, Ltd.In a relevant embodiment, employing be the hand-held spectrophotometer, like this, the technician can measure inside, oral cavity, be combined in the electromagnetism light wave (emission or absorb) of the probe on the tooth of early stage caries.Spectrophotometer can (Chiyoda-ku Tokyo) buys commercial hand-held from Konica Minolta company.
In some embodiments, probe is attached on the tooth of early stage caries pathological changes, probe sends fluorescence at the wavelength of visible-range, uses the camera tooth to detect emitted fluorescence.Photographing unit used herein is a device that is used for catching picture or continuous dynamic image.Be fit to detector probe photographing unit can (Dallas TX) buys from Texas Instruments.
The optical fiber that is used for fibre system is the category of Optical devices at this.Optical fiber comprises glass or plastic optical fibre, makes light along its total reflection transmission.Optical fiber is made up of the covering of fibre core and encirclement, the fibre core of the covering contact center high-index material that the material of one or more layers low-refraction is formed.Optical fiber shines a zone of dental surface at this guide wire as light, comprises the proximal surface between tooth.Optical fiber can comprise a relevant fibre bundle, also has lens usually simultaneously.
Previously known optical fiber is used for dentistry, as in the light polymerization of dental filling material compositions.Use hand-hold light source in the hardening process and send the blue light that wavelength is about 450nm, and the tooth in treating by fiber rod or fiber light cone arrival (SCHOTT NorthAmerica Inc., Southbridge, MA).These devices are applicable to test kit as herein described and method easily.
In this test kit, can use various method to make one or more probe contact dental surface.For example, can coat probe with thin layer or substrate earlier, be applied on the tooth again.Substrate can be a thin paper, plastic tape, or other any materials of conveniently applying ointment or plaster.In addition, the syringe of injection-type syringe is loaded onto probe solution, can be used for applying the probe solution of low capacity.Insert chock in the proximal surface zone and carry out pretreatment, enlarge two or more interdental spaces and can make the proximal surface zone be more conducive to treatment.
After probe contact tooth, before observing with Optical devices, this zone elder generation water washes once at least, removes excessive probes solution.
Another example that optical fiber is used for dentistry is the dental handpiece illumination.Dental instruments generally includes a light source that is used to illuminate area for treatment, and in order to reach this purpose, (MA), and this instrument is adapted to this purpose to the photoconduction of packing in dental handpiece for SCHOTT North America Inc., Southbridge.
Fig. 2 has shown the Optical devices that use in some embodiments in the present invention, and these Optical devices are used for detecting the experiment tooth sample that is combined in the early stage caries pathological changes or the probe in the section.The tooth that be combined with probe, is used for detecting early stage caries is placed on platform 4.Light source 1 is that (Asahi Spector China), sends rayed (promptly with absorbing wavelength or the emission wavelength irradiation) tooth regions of certain wavelength and comes the conjugate on the detector probe MAX301 xenon lamp.In some embodiments, (light wave directly focuses on the tooth regions on the platform 4 to optical fiber 5 then for Olympus, the MelvilleNY) light wave of transmission and focused light source 1 emission.Optical fiber 5 uses a silicon rubber cup or wrapper that the light wave correction is formed a kind of local irradiation.Photographing unit 2 is that (Texas Instruments, Dallas TX) are used for the image of Acquisition Detection probe to the MC285SPD-LOBO camera, be transferred to computer 3, Optiplex 201L (Dell, Round Rock, TX), computer 3 uses Capture eBase (Solution Systems, Inc., Rolling Meadows, IL) software, use software program control light source 1, can control the wavelength of light source 1, as control suitable emission light and excite probe as software.
Employed compositions of remineralization and method are well-known in dentistry, as, commercial product E namelon is the toothpaste that tubulose contains water-soluble phosphoric acid calcium, it can directly be applied on the tooth.Further add fluoride in Enamelon, comprise that a pipe contains the white toothpaste of calcium and the blue toothpaste that a pipe contains phosphate and fluoride, parallel extruding two pipe toothpaste carry out the remineralization treatment.Perhaps, one time dental clinic can be used one or more remineralization gels, as, once topical gels agent of treatment in every month contains the fluoride of 100-150ppm, wherein 2.72% acidulated phosphate fluoride and 2% neutral sodium fluoride.It should be noted the metering that provides far below toxic grade, and guarantee that the patient can not swallow gel.
Carried out illustration by abundant disclosed the present invention by the following examples and claim, described embodiment only plays the example effect and does not constitute further restriction.Here all lists of references of being quoted are all incorporated this paper into by quoting as proof here.
Embodiment
Tooth that embodiment 1. fluoroscopic examinations extract and top white macula.
The enamel sample that comprises a part of tooth is analyzed, confirmed that each sample contains one " white macula " at least, white macula is divided into two stages: the low and deep white macula of visible white macula and enamel surface, whether the illumination tooth detects automatic fluorescence and exists.Under ultraviolet, do not observe special fluorescence phenomenon automatically, data representation, there is not automatic fluorescence in the other parts of white macula and tooth, therefore, use the fluorescence radiation agent to detect white macula for the ease of observing.
The tooth sample that extracts was cultivated 60 seconds in tetracycline (1mg/ml), used phosphate buffer (PBS) flushing then.Observation sample under the ultraviolet (uviol lamp SB-4W) of wavelength 260nm.In addition, use the spectrophotometric hand-held probe of Olympus to detect fluorescence.The result is presented at the previous white macula position of determining that these teeth are combined with tetracycline and observes clear bright yellow fluorescence track.
Embodiment 2. histologic analysis
Albomaculatus tooth is carried out the ultramicroscope horizontal analysis, and the fluorescence area that obtains the cross section and be associated further carries out histologic analysis, like this, has the fluorescence position of early stage caries pathological changes to obtain confirming.
Dens Bovis seu Bubali is placed on soak in 10% the hydrochloric acid solution and cleaned up in 10 to 30 seconds, set up the test macro model of a dental caries: use tooth erosion gel (10% non-silica-based phosphoric acid corrodes gel) to corrode selected dental surface 30 seconds, keeping other does not have erosive sample as negative control.
. all specimen and negative control sample in gold colloidal total protein stain (Bole company, Hercules, CA) soak 20-30 second in, clean with distilled water then, further use silver-colored staining kit (Bole company) dyeing, this method comes from the method for Gottleib and Chavko development in (Anal Biochem 165:33,1987).All tooth samples shine under near-infrared (NIR) light and absorb.
The result shows, before soaking, carried out erosive specimen and shown that the silver gray in certain zone is painted, and negative control sample (not being etched) painted without any this respect, these data show that near infrared light is combined with the tooth sample of colloidal gold probe, has detected the early stage caries that comprises the interproximal caries pathological changes.
The oral cavity of dental patients or tongue chamber are with gargling 30 seconds as the tetracycline of 1mg/ml, after extensively cleaning, with irradiation under ultraviolet ray oral cavity or tongue chamber, detect the outward appearance and the position of each phosphor dot respectively with spectrophotometric hand-held probe, light-emitting zone or gray corrosion are taken pictures.
The oral cavity of dental patients or tongue chamber use colloidal gold solution (as the total protein dye liquor of Bole company, catalog number (Cat.No.) 170-6527) gargled 30 seconds, after water is gargled and is extensively cleaned, (Bole company) further gargles 20-30 second with silver-colored staining kit, use near infrared light (NIR) irradiation oral cavity or tongue chamber then, with the outward appearance and the position of spectrophotometric hand-held probe in detecting silver gray pigmented section, pigmented section is taken pictures.
After the detection, the remineralization effect is carried out in the position that early stage caries is arranged,, fluorion is joined diseased region as using topical gels agent or special toothpaste, remineralization is handled and can be recovered adamantine complete, induces calcium and phosphate to deposit on the enamel crystal of partly decalcifying.
Embodiment 6. uses Dens Bovis seu Bubali sample evaluating detector probe
The Dens Bovis seu Bubali section is obtained the enamel sample, but the dentin layer that does not comprise Dens Bovis seu Bubali, corrode enamel section sample and obtain the demineralization zone, the enamel slice surface that the demineralization zone is arranged is contacted the various probes of a series of concentration, the surface that is combined with probe is shone under one group of excitation wavelength at random, then observe emission, then, detect the trap of illumination wavelength, directly obtain the optical observation result, taking tooth or the indirect transfer of data that obtains from the probe of Optical devices to the Optical devices imager by eyes, spectrophotometer or camera.
Embodiment 7. uses from the tooth proximal surface model of human body extraction and assesses detector probe
Human teeth's (molar and nipper) the proximal surface model that extracts is to be assembled by the tooth preparation that uses the manufacturing of silicon impression material, when each tooth of preparation, (500nm is dark to adopt the proximal surface contact area to come interproximal caries enamel that preparation experiment uses, 1.5mm wide), adopt X-ray film (stinging fin) and microscope to assess the synthetic dental caries of preparation.
In initial contact method, use an infiltration that the adamantine zone of cotton balls contact interproximal caries of detector probe is arranged, probe shines under one group of excitation wavelength at random, then observe fluorescent emission, then, detect the trap of each probe under illumination wavelength according to circumstances, the optical observation result of each probe is as shown in table 1.
Table 1: the performance of detector probe
| Detector probe | Compositions | Detection method | Excite/absorb (nm) | Emission (nm) | Testing result |
| Bismuth | Metal | Absorbance | Absorb | Good | |
| Gold colloid | Metallic colloid | Absorbance | 530 | A little less than | |
| Amycin | Cancer therapy drug | Fluorescence | 480 | 630 | Good |
| Riboflavin | Vitamin B 2 | Fluorescence | 450 | 550 —700 | Good |
| Chlorophyll A | Chlorophyll | Fluorescence | 614 | 670 -900 | Good |
| Fox Green | Dyestuff | Fluorescence | 800 | 835 | A little less than |
| Porphyrin | Fluorescence | 600 | 700 | Good | |
| Luciferase/luciferin | Organic enzyme and protein | Chemical reaction fluorescence | 630 (PH) dependency | Good | |
| Qdot | Nanodot | Fluorescence | Good | ||
| HylightFlour | Micromolecular compound | Fluorescence | Good |
The face of facing enamel dental caries is all arranged on each tooth preparation, and illumination also takes pictures that each is combined with the tooth preparation of probe.Fig. 3 is the light absorption photo that is combined with the early stage caries pathological changes of bismuth probe on the tooth preparation.Fig. 4 is the fluorescence photo that is combined with the early stage caries pathological changes of amycin probe on the tooth preparation.Fig. 5 is the fluorescence photo that is combined with the early stage caries pathological changes of riboflavin probe on the tooth preparation.Fig. 6 is the fluorescence photo that is combined with the early stage caries pathological changes of chlorophyll A probe on the tooth preparation.Fig. 7 is the fluorescence photo that is combined with the early stage caries pathological changes of porphyrin probe on the tooth preparation.Fig. 8 is the organism luminous photo that is combined with the early stage caries pathological changes of luciferase/luciferin probe on the tooth preparation.
Embodiment 8. variable optimizations
Under different illumination intensity and different beam size, each probe is detected, observed data, change the concentration of detector probe, optium concentration under the time of contact of the detector probe of a suitable dental applications of acquisition, usually, the system of describing in utilization the foregoing description determines that be about 20 seconds the lasting time of contact of suitable dental applications, 40 seconds or 60 seconds.Detect luciferase and determine best fluorescent characteristic with the optical characteristics of fluorescein in different PH.The ability that detector probe is attached to dental surface has different face cavity conditions, as, plaque, gingiva, and calculus, soft tissue, and the compactness that contacts between the neighbour all will determine to use any in the system of describing in the foregoing description.
Claims (according to the modification of the 19th of treaty)
1. method that detects patient's early stage caries comprises:
Selective binding optical detection probe is on the dental caries of commitment pathological changes; Its middle probe comprises can be in conjunction with the molecule of dental caries; With
Use Optical devices to detect the dental caries that is combined with probe.
2. method according to claim 1, wherein detect selective binding and also comprise the step that is selected from the following group of forming: tooth contact fluorescent probe, wherein fluorescent probe is selected from the group of being made up of tetracycline, Hylight Fluor, Qdot, Fox Green, amycin, riboflavin, chlorophyll and porphyrin, use the excitation wavelength illumination of teeth, wherein diagnosis is to detect the emission of the light wave in certain zone under excitation wavelength; Tooth contact probe, its middle probe are luciferases and further make tooth contact fluorescein and ATP that wherein diagnosis is that the certain regional organism of detection is luminous; Tooth contact gold colloidal, wherein diagnosis is to detect the near infrared light (NIR) in certain zone to absorb; Tooth contact quantum dot compositions probe, wherein diagnosis is to detect fluorescence or fluoroscopic examination dichroism; The probe of tooth contact conjugation quantum dot compositions, wherein this conjugate is in conjunction with second kind of reagent, and reagent is selected from the group of being made up of tetracycline, bismuth, gold colloidal or its analog, detects fluorescence or fluoroscopic examination dichroism then; Tooth contact gold colloidal, wherein diagnosis is to use HiLyte Fluor 750 hydrazide (a kind of novel fluorescence dyestuff) to detect fluorescence.
3. method according to claim 1, wherein early stage caries refers to the stage early than cavitation or further demineralization.
4. method according to claim 2 is wherein observed by photometry and is detected dental caries.
5. method according to claim 2, wherein dental caries selective binding tetracycline probe is used to observe white macula.
Claims (52)
1. method that detects patient's early stage caries comprises:
Selective binding optical detection probe is on the dental caries of commitment pathological changes; Detect the dental caries that is combined with probe with use one Optical devices.
2. method according to claim 1, wherein detect selective binding and also comprise the step that is selected from the following group of forming: tooth contact fluorescent probe, wherein fluorescent probe is selected from the group of being made up of tetracycline, Hylight Fluor, Qdot, Fox Green, amycin, riboflavin, chlorophyll and porphyrin, use the excitation wavelength illumination of teeth, wherein diagnosis is to detect the emission of the light wave in certain zone under excitation wavelength; Tooth contact probe, its middle probe are luciferases and further make tooth contact fluorescein and ATP that wherein diagnosis is that the certain regional organism of detection is luminous; Tooth contact gold colloidal, wherein diagnosis is to detect the near infrared light (NIR) in certain zone to absorb; Tooth contact quantum dot compositions probe, wherein diagnosis is to detect fluorescence or fluoroscopic examination dichroism; The probe of tooth contact conjugation quantum dot compositions, wherein this conjugate is in conjunction with second kind of reagent, and reagent is selected from the group of being made up of tetracycline, bismuth, gold colloidal or its analog, detects fluorescence or fluoroscopic examination dichroism then; Tooth contact gold colloidal, wherein diagnosis is to use HiLyte Fluor 750 hydrazide (a kind of novel fluorescence dyestuff) to detect fluorescence.
3. method according to claim 1, wherein early stage caries refers to the stage early than cavitation or further demineralization.
4. method according to claim 2 is wherein observed by photometry and is detected dental caries.
5. method according to claim 2, wherein dental caries selective binding tetracycline probe is used to observe white macula.
6. method according to claim 2, wherein the dental caries of selective binding quantum dot probe is a translucent enamel fluorescence speckle.
7. method according to claim 3 is wherein diagnosed Lycoperdon polymorphum Vitt, silver color, white or brocken spectrum at 50-100 μ m under enamel surface or the surface on interior bottom.
8. method according to claim 1, wherein dental caries is between the neighbour.
9. method according to claim 1, wherein before contact, the proximal surface zone can enter by at least a method that is selected from down in the group: insert an escapement, wrap up probe with metal or plastic tape when probe is inserted the proximal surface zone.
10. method according to claim 9, wherein conjugate comprises a quantum dot compositions or HiLyte Fluor 750 hydrazide.
11. method according to claim 9, wherein gold colloidal comprises the gold nano ball particle.
12. method according to claim 9, wherein the Tetracyclines fluorescent probe comprises a kind of in chlortetracycline, oxytetracycline and the doxycycline at least.
13. method according to claim 9 wherein continues time of contact and was at least 40 seconds or 60 seconds 20 seconds.
14. according to each described method among the claim 4-6, wherein the position of dental caries is indicated in Lycoperdon polymorphum Vitt, silver color, white or brocken spectrum zone.
15. according to each described method among the claim 4-6, wherein the size in Lycoperdon polymorphum Vitt, silver color, white or brocken spectrum zone is indicated the degree of dental caries.
16. according to each described method among the claim 1-5, wherein Optical devices are Optical devices in the hand held oral.
17. according to each described method among the claim 4-6, wherein the device used of fluoroscopic examination is selected from the group of following formation: uviol lamp or be connected hand held oral probe on the spectrophotometer.
18. method according to claim 1 also is included in before the contact, detects the existence of automatic fluorescence.
19. method according to claim 1 also comprises by remineralization and solidifies the dental caries that detects.
20. method according to claim 1, wherein detecting target is mammal.
21. method according to claim 1, wherein detecting target is the people.
22. method according to claim 1 also comprises the photographs that preparation is combined with the dental caries scope of probe.
23. method according to claim 1 also comprises remineralization dental caries pathological changes, comprising monitoring and prevent or reduce the dental caries pathological changes.
24. method according to claim 1, wherein the optical detection probe is electrically charged.
25. method according to claim 2, wherein fluorescent probe is a tetracycline, and the illumination wavelength of tooth is about 350nm-450nm, and the detection wavelength of fluorescence is about 450nm-600nm.
26. method according to claim 2, wherein fluorescent probe is Hilyte Fluor, and the illumination wavelength of tooth is about 720nm-750nm, and the detection wavelength of fluorescence is about 750nm-800nm.
27. method according to claim 2, wherein fluorescent probe is Qdot, and the illumination wavelength of tooth is about 400nm-750nm, and the detection wavelength of fluorescence is about 750nm-900nm.
28. method according to claim 2, wherein fluorescent probe is a Fox Green, and the illumination wavelength of tooth is about 750nm-800nm, and the detection wavelength of fluorescence is about 820nm-870nm.
29. method according to claim 2, wherein fluorescent probe is an amycin, and the illumination wavelength of tooth is about 400nm-500nm, and the detection wavelength of fluorescence is about 600nm-700nm.
30. method according to claim 2, wherein fluorescent probe is a riboflavin, and the illumination wavelength of tooth is about 400nm-500nm, and the detection wavelength of fluorescence is about 500nm-700nm.
31. method according to claim 2, wherein fluorescent probe is a chlorophyll A, and the illumination wavelength of tooth is about 600nm-650nm, and the detection wavelength of fluorescence is about 670nm-900nm.
32. method according to claim 2, wherein fluorescent probe is a porphyrin, and the illumination wavelength of tooth is about 550nm-650nm, and the detection wavelength of fluorescence is about 650nm-750nm.
33. method according to claim 2, its middle probe comprises luciferase, fluorescein and ATP, and wherein the luminous detection wavelength of organism is about 600nm-800nm.
34. method according to claim 2, its middle probe are gold colloidal, wherein the detection wavelength of absorbance is about 500nm-800nm.
35. method according to claim 2, its middle probe are bismuth, wherein the detection wavelength of absorbance is about 500nm-800nm.
36. a test kit that detects early stage caries wherein comprises the detector probe that is attached on the dental caries, also comprises a kind of container and the positive control tooth sample of early lesion is arranged.
37. a test kit that detects early stage caries wherein comprises the probe that at least one is selected from down group: gold colloidal, fluorescent probe, organism is luminous; Its middle probe is attached on the dental caries selectively, and test kit also comprises a kind of container and the positive control tooth sample of early lesion is arranged.
38., also comprise the operation instructions of Optical devices according to claim 36 or 37 described test kits.
39. test kit according to claim 36, wherein fluorescent probe is tetracycline or tetracycline conjugate.
40. test kit according to claim 36, wherein fluorescent probe is selected from the group of following formation: Fox Green, amycin, riboflavin, chlorophyll and porphyrin.
41. a test kit that detects early stage caries, comprising detector probe, Optical devices and container.
42., also include the positive control tooth sample of early lesion according to the described test kit of claim 41.
43., also comprise operation instructions according to claim 41 or 42 described test kits.
44. according to the described test kit of claim 41, wherein Optical devices be selected from down at least the group in a kind of: hand held oral light wave checkout gear, camera and fiber optic devices.
45. according to the described test kit of claim 41, wherein optical detection apparatus also comprises electromagnetic wave transmitter, wherein the wavelength of Chan Shenging is used for the fluorescence excitation probe.
46. according to the described test kit of claim 41, its middle probe be selected from down at least the group in a kind of: fluorescent composition and organism light emitting composition.
47. according to the described test kit of claim 46, wherein the organism light emitting composition is selected from down a kind of in the group at least: luciferase, the mixture of fluorescein and they.
48. according to the described test kit of claim 46, wherein fluorescent probe be selected from down at least the group in a kind of: Fox Green, amycin, riboflavin, chlorophyll and porphyrin.
49. according to the described test kit of claim 41, its middle probe be selected from down at least the group in a kind of: Qdot, gold colloidal, and bismuth.
50. according to claim 36, each described test kit in 37 and 41, its middle probe is a unit dose.
51., wherein further comprise the probe applicator according to the described test kit of claim 41.
52. according to the described test kit of claim 51, its middle probe applicator be selected from down at least the group in a kind of: aerosol apparatus, bite wing can be extruded colloidal compressed pipe.
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| CN108601851B (en) * | 2015-10-21 | 2021-11-16 | 密歇根大学董事会 | Detection and treatment of caries and microcavities with nanoparticles |
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