CN108369169A - The device and method of growth or dissolution kinetics for measuring colloidal solid - Google Patents
The device and method of growth or dissolution kinetics for measuring colloidal solid Download PDFInfo
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- CN108369169A CN108369169A CN201680060558.6A CN201680060558A CN108369169A CN 108369169 A CN108369169 A CN 108369169A CN 201680060558 A CN201680060558 A CN 201680060558A CN 108369169 A CN108369169 A CN 108369169A
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/02—Investigating particle size or size distribution
- G01N15/0205—Investigating particle size or size distribution by optical means
- G01N15/0211—Investigating a scatter or diffraction pattern
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N13/00—Investigating surface or boundary effects, e.g. wetting power; Investigating diffusion effects; Analysing materials by determining surface, boundary, or diffusion effects
- G01N2013/006—Dissolution of tablets or the like
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N2015/0038—Investigating nanoparticles
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N2015/0042—Investigating dispersion of solids
- G01N2015/0053—Investigating dispersion of solids in liquids, e.g. trouble
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Abstract
A kind of system for determining growth/rate of dissolution of colloidal solid is disclosed, the system comprises multiple light sources and multiple sensors.Light source is configured to emit electromagnetic radiation beam at the sample room for accommodating the colloidal solid.The sample room allows the part for combining beam vertical or with some other angle to the combination beam divergence.The scattered portion of the beam is directed to the sensor of detection electromagnetic radiation.The sensor is connected to the processor for activating the light source and obtaining image from the sensor.Multiple images are shot at a time interval, and for each image of shooting, calculate total image intensity levels, and be normalized.Then, the formula for being fitted normalized value at any time is calculated, and slope is determined according to the formula.
Description
Technical field
The present invention relates to using the microscope equipped with digital camera measuring to the particle in liquid sample and
Observation.
Related application
This application claims entitled " the APPARATUS FOR MEASUREMENTS OF submitted on October 14th, 2015
The U.S. Provisional Patent Application of GROWTH OF DISSOLUTION KINETICS OF COLLOIDAL NANOPARTICLE "
The priority of No.62/241354.The application also requires on 2 8th, the 2016 entitled " MULTI-CAMERA submitted
APPARATUS FOR OBSERVATION OF MICROSCOPIC MOVEMENTS AND COUNTING OF PARTICLES
The part continuation application of the U.S. Patent Application No. 15/018532 of IN COLLOIDS AND ITS CALIBRATION ",
Entitled " the SPECIAL PURPOSE CUVETTE ASSEMBLY AND METHOD FOR submitted on June 28th, 2016
The U.S. Patent application No.15/194,823's of OPTICAL MICROSCOPY OF NANOPARTICLES IN LIQUIDS "
The priority of part continuation application, during the disclosure of which is incorporated herein by reference in their entirety.
The U.S. that the application further relates to entitled " the NANOPARTICLE ANALYZER " that is submitted on June 3rd, 2015 is special
Sharp application number No.14/730,138, during the disclosure of which is incorporated herein by reference in their entirety.
Background technology
Nano particle (diameter be less than 1 micron of particle) is ubiquitous, is most rich in natural environment so far on the earth
Rich graininess entity, is widely used in and the relevant many applications of mankind's activity.There are many plant naturally occurring nano particle and
Artificial (design) nano particle.Nano particle appears in air, aquatic environment, rainwater, drinking water, biofluid, drug, drug
In conveying and treatment product and various industrial products.Nano particle typically occurs in polydispersion aggregation, special
Sign is there is various sizes of particle jointly, including those diameters are more than 1 micron of particle.
In view of being widely used for nano particle, the ability of its property of control and accurate characterization may be useful to many applications.
For measure the conventional method of nano particle property for mix nanoparticle size polydispersion sample (its in numerous applications
It is very common) it may be inaccurate.Due to measuring the light scattered from all nano particles simultaneously, when there are a series of particle sizes
When, it may be difficult to nano particle is resolved into it and forms size.Other methods also fail to solve by a series of nanoparticle sizes
The greatest differences problem of scattered light intensity caused by interior various sizes of nano particle.In these methods, it may not be possible to examine
Measure the low scattered signal for carrying out nano particle from childhood, or the high scattered signal from larger nano particle may make from compared with
The signal ambiguity of small nano particle.And in other methods, measurement result cannot illustrate the growth rate or rate of dissolution of particle,
Therefore the snapshot of Size Distribution may be inaccurate after a few minutes.Due to these defects, the nanometer of any intended size
Grain concentration and therefore entire Size Distribution are it is possible that unknown error.
The method of these detection nano particles (and larger particles) is commonly referred to as dark-field microscope method.Carry out this point
The instrument of analysis generally includes a small container (for example, cuvette), by the small container, can use the narrow light accurately limited
Piece carrys out irradiating liquids, and observes the scattering light from nano particle, usually observes relative to mating plate plane into an angle of 90 degrees
(but being not required).It is noted that viewing angle is not necessarily 90 degree；It is important that observing scattering light.It is caught by video camera
The light scattered by particle is caught, various sizes of particle can be visualized, wherein the size depending on particle, image has not
Same size and intensity (the various brightness of pixel).
In the U.S. for entitled " NANOPARTICLE ANALYZER " (" Stramski ") that on June 3rd, 2015 submits
Patent application No.14/730 (is hereby incorporated by reference in its entirety.) in 138, by using multiple light sources and monochrome
Video camera records the scattering light of several different colours simultaneously by Baeyer (Bayer) voxel model and solves these problems, Baeyer
Pattern corresponds to additive color three primary colors usually used in photography.In Stramski methods, final image is set from single record
Standby acquisition, therefore the image of the identical colloid block of different colours is recorded in the same area of recording equipment or sensor, from
And pixel is caused to be numbered relative to single origin (being typically a corner of sensor in camera).This so that processing is different
The image of color is possibly realized, since it is observed that the position of particle provided in identical coordinate system.Regrettably,
Stramski solves the problems, such as the growth or dissolving of particle without discussing or disclosing any method.
Entitled " the MULTI-CAMERA APPARATUS FOR OBSERVATION OF submitted on 2 8th, 2016
MICROSCOPIC MOVEMENTS AND COUNTING OF PARTICLES IN COLLOIDS AND ITS
The U. S. application 15/018,532 of CALIBRATION " (" Tatarkiewicz ") is overcome by introducing calibration mask
Some defects of Stramski, this method can be aligned the image from various light sources so that more acurrate to the processing of image.But
It is that Tatarkiewicz also solves the problems, such as the growth or dissolving of particle without discussing or disclosing any method.
Growth/dissolving of particle may be paid special attention to by industry-by-industry.For example, drugmaker may wish to confirm
Its drug is dissolved with specific rate, so as to use drug with effective time release mode.Moreover, when grain dissolution at
Nanoscale and when will not recombine the particle for being grown to bigger, this dissolving may be most to have therapeutic effect.Another family
Drugmaker may it needs to be determined that make new drug based on protein crystallize needed for time, the new drug can be used as big crystal with
Higher doses delivers.Therefore, although the method and apparatus disclosed in Stramski and Tatarkiewicz potentially contribute to obtain
The snapshot of drug particle size distribution, but it is not helped for providing rate of dissolution (or opposite growth rate).
Therefore, it is necessary to growth/dissolution kinetics of the effectively measuring colloidal solid of improved system energy.
Invention content
A simplified abstract is provided below, in order to provide the basic reason of some aspects to theme claimed
Solution.Originally it plucks and is summarized if it were not for extensive, be not intended to determining key/critical element or describe the model of theme claimed
It encloses.The purpose is to introduce some concepts in simplified form, as the preamble in greater detail introduced later.
Equipment, system and method described herein grazioso solve the above problem.It discloses a kind of for determining glue
The system of growth/rate of dissolution of body particle, the system comprises multiple light sources and multiple sensors.Light source is configured to holding
It receives and emits electromagnetic radiation beam at the sample room of the colloidal solid.Sample room allows the part scattering for combining beam.Beam
Scattered portion is directed to the sensor of detection electromagnetic radiation.The sensor is connected to the activation light source and from the sensing
Device obtains the processor of image.Multiple images can be shot at a certain time interval, and for each image, are calculated total
Light intensity levels (summations of all intensity recorded at all pixels), then by the maximum intensity rank in the sequence,
It is normalized.For each time point, the average intensity value of multiple images is obtained.Then, fitting normalization at any time is calculated
The formula of value, and slope is determined according to the formula.Moreover, instead of shooting static image, Ke Yi with specified time interval
The time interval shoots one group of image (that is, video).The average value of the intensity summation of each video and each time interval is calculated,
Then, it is normalized by the maximum intensity value in sequence.
Measurement window can also be arranged in processor, which limits the amount of images of shooting.The measurement window can
With the total number of images based on total time span or acquisition.It can also be based on calculated slope.When total image intensity levels
When more than maximum intensity rank, maximum image intensity rank can be further arranged in processor, and adjusts the time for exposure of sensor.
The equipment can use the multiple light sources with multiple wavelength, and be partial to only detect one in multiple wavelength
Multiple sensors of wavelength.The system can use the combination for forming beam combination before scattered beam part reaches sensor
Structure and light beam decomposition texture (or beam splitter).Multiple light sources can be single multi wave length illuminating source.Sensor can also be can
To detect the single sensor of multiple wavelength.
If calculated slope is negative value, then it represents that colloidal solid dissolves, if it is positive value, then it represents that colloidal solid
Growth.
Also disclosed herein it will be apparent to those skilled in the art that other aspects, alternative solution and change
Change form, and it is specifically envisaged that be include for the present invention a part.The present invention is only in Patent Office in the application or related Shen
It please be illustrated in the middle claim allowed, and certain exemplary summing-ups descriptions are in no way limited below, is fixed
Range that is adopted or determining legal protection in other ways.
Description of the drawings
The present invention may be better understood with reference to the following drawings.Component in attached drawing is not drawn necessarily to scale, but will
Focus on the exemplary aspect for being clearly shown the present invention.In the accompanying drawings, run through different view and/or embodiment, it is identical
Reference numeral indicates corresponding part.It should be understood that certain components and details may not occur in the accompanying drawings to help
In the more clearly description present invention.
Figure 1A shows a kind of system detecting the electromagnetic radiation from cuvette using single wavelength source.
The system that Figure 1B shows the electromagnetic radiation for detecting two kinds of wavelength.
Fig. 1 C show a kind of system for detecting the electromagnetic radiation of three kinds of wavelength.
Fig. 2 is the relational graph for showing scattering coefficient and particle diameter.
Fig. 3 A are the normalization overall strength for showing particle in colloidal solution and the relational graph of time, illustrate to dissolve.
Fig. 3 B are the normalization overall strength for showing particle in colloidal solution and the relational graph of time, illustrate to grow or tie
It is brilliant.
Fig. 3 C are the normalization overall strength for illustrating particle in colloidal solution and the relational graph of time, illustrate to grow or tie
Brilliant and subsequent dissolving.
Fig. 4 is the flow chart for the method for depicting growth/rate of dissolution for determining colloidal solid.
Specific implementation mode
Implement the present invention herein with reference to some specific examples of the present invention, including inventor and imagine any best
Pattern.The example of these specific embodiments is shown in the accompanying drawings.Although describing the present invention in conjunction with these specific embodiments, answer
Understand, this is not intended to limit the invention to described or explanation embodiment.On the contrary, its be intended to covering may include by
Alternative solution, modification in the spirit and scope of the present invention defined in the appended claims and equivalent program.
In the following description, numerous specific details are set forth in order to provide thorough understanding of the present invention.Can not have
Implement the specific example embodiments of the present invention in the case of some or all of these details.In other cases, do not have
Processing operation well known to those skilled in the art is had a detailed description, in order to avoid unnecessarily obscure the present invention.For the sake of clarity, originally
The various technologies and mechanism of invention will describe in the singular sometimes.It is to be noted, however, that unless otherwise stated,
Some embodiments include the successive ignition of a kind of technology or number of mechanisms.Similarly, method shown and described herein is each
A step not necessarily executes in the order shown, or does not execute in certain embodiments.Therefore, discussed herein
Some realizations of method may include than shown or described more or less steps.In addition, the technology and machine of the present invention
Connection between two or more entities, relationship or communication will also be described when being formed with.It should be noted that the company between entity
Connect or relationship do not necessarily mean that direct, without hindrance connection because various other entities or process there may be or hair
It is born between any two entity.Therefore, unless otherwise stated, instruction connection be not necessarily mean that it is direct, unimpeded
Without hindrance connection.
The following list of example feature corresponds to Fig. 1-4, and is provided for the ease of reference, wherein entire
Identical reference numeral indicates corresponding feature in the description and the appended drawings：
System 10A, for detecting the electromagnetic radiation from cuvette using Single wavelength.
System 10B, the electromagnetic radiation for detecting multiple wavelength.
Alternative system 10C, the electromagnetic radiation for detecting multiple wavelength.
Light source 15.
The first light source 15A of first wave length.
The electromagnetic radiation beam 20 launched from light source.Substantially the first electromagnetic radiation beam 20A of first wave length.
The substantially second light source 25 of second wave length.
The substantially electromagnetic radiation beam 30 of second wave length.
The third light source 32 of third wavelength.
The substantially third electromagnetic radiation beam 34 of third wavelength.
Beam composite structure/dichroscope 35.
Second beam composite structure/dichroscope 37.
Combine beam 40.
Mating plate shaper 45.
Sample room/cuvette 50.
Broad light 55.
A part of 55A of the third radiation of scattering.
Image-forming objective lens 60.
Beam splitting structure/dichroscope 65.
The scattered-out beam 70 of directive imaging sensor.
The first wave length of separation radiates 70A.
Imaging sensor 75.
First sensor 75A is partial to the electromagnetic radiation that detection is substantially first wave length.
The second wave length radiation 80 of separation.
Second sensor 85 is partial to the electromagnetic radiation that detection is substantially second wave length.
The third wavelength radiation 86 of separation.
3rd sensor 87 is partial to the electromagnetic radiation that detection is substantially third wavelength.
Second beam splitting structure/dichroscope 88.
Processor 90.
Line of best fit 95 with constant-slope.
Line of best fit 100 with variable slope.
Method 405 for the growth/rate of dissolution for determining colloidal solid.
Each step 410-500 of method.
A referring to Fig.1 shows the system 10A for detecting the electromagnetic radiation from cuvette.System 10A includes
Single source 15, the single source emit electromagnetic radiation beam 20 at mating plate shaper 45.Obtained mating plate is pointed to receiving
Sample room/cuvette 50 containing colloidal solid (i.e. nano particle or micrometer-sized particles (not shown)).It is this transparent small
Container can be according to entitled " the SPECIAL PURPOSE CUVETTE ASSEMBLY AND submitted on June 28th, 2016
The U.S. Patent Application No. 15/ of METHOD FOR OPTICAL MICROSCOPY OF NANOPARTICLES IN LIQUIDS "
194, No. 823 construct, and content is incorporated herein by reference.
When shock is present in the particle in the colloidal solution in cuvette 50, the part scattering 55 of mating plate, and
And usually can by focal imaging object lens 60 (such as microscope equipped with another long reach object lens) with an angle of 90 degrees into
Row observation.It is noted that viewing angle is not necessarily 90 degree；It is important that observing scattering light.Leave dissipating for image-forming objective lens 60
It penetrates light and reaches sensor 75, which is connected to processor 90.
Figure 1B and 1C is shown obtains more steady system using different wavelength and wavelength sensor.Use multiple waves
The benefit of long light is to expand the range of detectable particle size.Specifically, scattering light intensity very strongly according to
Rely in particle size, such as changes many orders of magnitude between the nano particle of 10nm and 1000nm diameters.Typical sensor
8 bits or 256 different values are distributed for each pixel and each color, and zero corresponds to Unrecorded light, and peak 255
Corresponding to maximum brightness, this depends on the gain for system setting and exposure.If the light that any pixel receives is both greater than
Corresponding to the maximum level of value 255 (saturation), then except through reducing detector gain or shortening the time for exposure, to own
Except the intensity-conversion of record is at lower value, it is impossible to distinguish and record such value.Although reduce gain or shorten exposure
Between might have help distinguish make sensor be saturated particle, but these adjustment can also reduce sensor spectrum bottom end (i.e. compared with
Small particle) sensitivity.
Since the typical sizes (diameter is less than 1 micron) of nano particle are suitable with visible wavelength, system can not area
The details of light splitting scattering nano particle, but only record the overall strength of the light scattered as each particle projects image, the figure
Circular spot or disk as looking like several pixels in covering sensor.The intensity of the visible light scattered on nano particle
It is depicted as in fig. 2 for a kind of wavelength and a kind of particle with specific refractive index, the function of the diameter of scattering particles is (right
In the 450 nm optical wavelength and in water polystyrene spheres with refractive index n=1.6 use so-called an angle of 90 degrees Mie scattering reasons
By being calculated).It is less than the particle of 100nm for diameter, scattering strength becomes very small, it is difficult to detect.
In addition, the scattering efficiency of particle depends on the wavelength of exposure light；Therefore detection range also depends on wavelength.Pass through
Detect using the multiple light sources with different wave length and respectively these wavelength (such as Stramski and Tatarkiewicz patents
In 3 kinds of colors telling about：Red, green and blue), operator can be by covering broader recorded particle size model
It encloses, to be significantly expanded the dynamic range of system.
With reference to figure 1B, the example apparatus using multiple wavelength as described in Tatarkiewicz patents is shown, this is specially
Profit is herein incorporated by reference.Such system 10B may include the first light source and second wave length 25 of first wave length 15A
Second light source, two lasers such as with different light beams colors or wavelength.Can also have can generate multiple wavelength
Light single source.
Each in the two light beams is directed into composite structure 35 (such as dichroscope), will come from light source
15,25 light beam is combined into single beam combination 40, and beam combination 40 is guided to the light of such as mating plate shaper 45 etc
System.Mating plate shaper 45 may include cylindrical lens and form the long reach object lens of very narrow illumination mating plate.
Mating plate can be directed to transparent sample room 50 (such as cuvette).
One of the beam combination of scattering 55A when shock is present in the particle in the colloidal solution in cuvette 50
Point have wavelength identical with the illumination light from mating plate shaper 45, usually can by focal imaging object lens 60 (such as with
Have the microscope of another long reach object lens) it is observed with an angle of 90 degrees.It is noted that viewing angle is not necessarily 90
Degree；It is important that observing scattering light.Leave beam splitting knot of the scattering light in such as second dichroscope etc of image-forming objective lens 60
Composition wavelength is split into structure 65, that is, the first wave length radiation 70A of separation and the second wave length radiation 80 of separation, they can
Independently to reach two sensor 75A, 85 those of (are such as arranged in digital gray scale camera), these sensors 75A, 85
Suitable for detecting the electromagnetic radiation of substantially the first and second wavelength 15A, 25 respectively.The two sensors can also be a list
One sensor can detect the electromagnetic radiation of multiple wavelength.
The lighting source 15,25 of more multi-wavelength is more combined and divides to dichroscope 35,65 appropriate by addition,
The system can be easily extended to more multi-wavelength and more corresponding sensor 75A, 85.It is shown in Fig. 1 C such
Exemplary system 10C shows three wavelength systems of the third light source with third wavelength 32, and it is substantially third to generate
The third electromagnetic radiation beam of wavelength 34, further it is shown that the second composite structure/dichroscope 37.In the detection side of system 10A, second
Beam splitting structure/dichroscope 88 detaches third wavelength radiation 86 so that third wavelength radiation 86 can be detected by 3rd sensor
It arrives, which is partial to the electromagnetic radiation that detection is substantially third wavelength 87.Sensor (75A, 85 and 87) can be with
It is connected to processor 90, which handles the image detected by sensor (75A, 85 and 87).
As previously mentioned, for each pixel and each wavelength, intensity is recorded as number by sensor, usually by 8 bit numbers
Word (correspond to 256 different values) distributes to each pixel and each wavelength, and zero corresponds to unwritten light, and peak
255 correspond to maximum brightness.The final image obtained from sensor is made of the character matrix stored, is corresponded on sensor
Available all pixels, usually more than 1,000,000.By being added all these numbers, using the total brightness of image as single
Number (when using multiple wavelength, for each wavelength, individually there are one numbers).By in preselected time (usually with fixation
Time interval) shooting image, obtain the Serial No. for the time-evolution that one indicates luminous intensity scatter by particle, but with deposit
It is that quantity and the size of the particle in analyzed colloid are proportional.
As shown in Figure 3A, pass through figure of such value relative to the time being plotted in after being normalized to initial value, energy
Enough estimate colloid present in dissolving or growth process and due to some chemically or physically process and undergo dissolving or growth
Process rate of dissolution or amounts of particles and size growth (i.e. dynamics).Line 95 is the best fit of figure, the line
Slope is negative value-expression dissolving.Moreover, the slope of line 95 is also represented by the single average production in entire observing time/dissolving speed
Rate.More complicated line 100 can the data-that change over time of fit slope for example, the slope in first minute of line 100 is precipitous, and
Become less serious within rear a few minutes.This shows that colloidal solution quickly dissolves in first minute, and dissolving is slow thereafter.It fills
Divide characterization growth/rate of dissolution may be highly useful in commercial Application (such as in pharmaceutical industry).Dissolving or growth curve
Slope is usually related to so-called procedural order, for example, rate of dissolution linear time dependency (when data are plotted as drug
When release or crystallization content are to the logarithm of time) it indicates first order reaction process or discharges the drug dose of drug and the unit interval discharges
The proportional process of medication amount shorten.
Fig. 3 B show that the normalized intensity of different colloidal solution changes with time, and show that particle is growing-ties
Brilliant or aggregation.Line 105 is the best fit of the specific curves, and line 105 has inflection point in region 110, this shows at this
Time memory is in mass crystallization or aggregation.Fig. 3 C are another curve graphs of the intensity versus time of another colloidal solution, indicate knot
Then brilliant or aggregation is dissolved after colloid changes and (some salt for changing pH value is such as added).
Turning now to Fig. 4, the method 405 of growth/rate of dissolution by description for determining colloidal solid.It should pay attention to
, this method describes step by step, it should be apparent to those skilled in the art that the sequence of step can
To change and still fall in the range of following claims.
In step 410, colloidal solution is inserted into sample room, for example, cuvette.Step 415,420 and 425
For the multiple variables of measure setup, including amount of images, the time delay between image and the time for exposure to be shot.Image it
Between delay and the combination of the amount of images to be shot define measurement window.This can preset or as described below, also may be used
To be dynamic.
This method can have optional step 430-460, to solve the sensitivity problem of system.Specifically, in step
Maximum image intensity rank is set in rapid 430, in step 435-445, activating light source, and in step 450, capture images with
Determine total image intensity levels of image.If in step 455, total image intensity levels are more than maximum figure in step 450
As intensity rank, then system will shorten the time for exposure in step 460, and repeat step 435-455, until total figure is as intensity level
Not Di Yu maximum image intensity rank, at this point, system is since step 465, to obtain image and intensity rank, and according to these
Determine growth/rate of dissolution.This helps to prevent bulky grain from making image supersaturation, image supersaturation often make system without
Method detects the case where smaller particle, to have a negative impact to the efficiency and range of system.
Step 430-460 is as option, it is convenient to omit, method can leap to step 465 from step 425, activation
First and second light sources (or single source, if using single source equipment, as shown in Figure 1A as), the duration is
Time for exposure (step 465), obtain the first and second images (or in single source device, single image) (step 468 and
470).Then, system postpones preset time period between images, and determines whether in step 480 to have reached amount of images.Such as
Fruit has reached total number of images, it is determined that total image intensity levels of each image, and it is normalized (step 485 and
490), and determine that the formula (step 95) for being fitted the normalized value calculates slope (step 500) according to the formula.Normalization
Process includes finding out the maximum intensity of all pixels in image (counting), then by the bout all intensity (counting) divided by
The quantity.
In step 468 and 470, by obtaining short-sighted frequency rather than single image, method 405 can be more steady.If
It completes, then it, can be with the mean intensity number of each video in the sequence of calculation (that is, video to each time interval in step 486
In each frame/image overall strength divided by frame number/picture number in video), then, which is normalized.By holding
Row step 486, method 405 can shoot image or video in each time interval, without partially right in normalization
Some image assigns higher weight.Alternatively, if video is used only for method 405 and each video is by identical quantity
Frame/image composition, then can use and normalize the intensity of all pixels in all frame/images in each video；To
Skip step 486.
It should be noted that the system can be not provided with the sum of image/video to be achieved (that is, step 415)；System
Total cost time can be set, and step 480, which can check whether, has reached total cost time.In addition, processor can be with
With shooting image total image intensity value and slope are determined (that is, after step 470) at substantially the same time.This permission system has one
A dynamic overall measurement window.Specifically, if solution is reduced in first minute with basic rate, then, it is stabilized to close
Like linear function (as shown in Figure 3A), then this method almost can execute step (that is, after step 470) simultaneously with shooting image
Rapid 485-500, and step 480 can be based on the inquiry whether changed about identified slope.If do not changed,
This method can stop measuring.
It is also to be noted that the delay between image/video can also be dynamic.For example, if processor and bat
It takes the photograph image and almost determines total image intensity value and slope (that is, after step 470) simultaneously, then it can almost be determined tiltedly simultaneously
Rate.If the slope is very big or quickly changes (first part of curve graph in such as Fig. 3 A), shorten subsequent image/video
Between it may be advantageous delay time-in other words, more sample images/regard are obtained when colloidal solution is rapidly changing
Frequently.Permission system is more accurately measured slope by this when growth/rate of dissolution is most unstable.When rate starts to stablize and becomes
When obtaining less variable, then it can increase the delay between image/video.
Although the embodiments herein is related to nano particle, same procedure disclosed herein and device can also be applied to larger
Particle, such as micron-scale and bigger (even greater than 100 microns)；Therefore, claim below is not limited only to nanometer
Grain.
While characterized as exemplary embodiment of the present invention and application, including as described above and show in included
Shown in illustration, it is not intended that limiting the invention to these exemplary embodiments and application or being limited to exemplary
The mode or described mode of embodiment and application operating.In fact, it is aobvious for those of ordinary skill in the art and
It is clear to, many change and modification of exemplary embodiment is all possible.The present invention may include any device, knot
Structure, method or function, as long as obtained device, system or method are fallen into is based on present patent application or any correlation by Patent Office
In the range of one of permitted claim of patent application.
Claims (23)
1. a kind of system for determining growth/rate of dissolution of colloidal solid, the system comprises：
It is configured to emit the light source of electromagnetic radiation beam at sample room, the sample room is configured to accommodate the colloidal solid
And allow the part scattering of the beam；
The scattered portion of the beam is directed into sensor, wherein the sensor is adapted to detect for the electromagnetic radiation；
It is connected to the processor of the sensor, the processor is configured as executing following steps：
A. the light source is activated；
B. image is obtained from the sensor；
C. step (a) and (b) are repeated at a certain time interval；
D. for each image obtained in step (b), total image intensity levels are determined；
E. to each rank determined in step (d), total image intensity levels are normalized；
F. the formula of the normalized value of digital simulation step (e)；And
G. the slope of the formula of step (f) is calculated.
2. the system as claimed in claim 1, the wherein described image in step (b) include the video for having multiple images.
3. system as claimed in claim 2, wherein the total figure includes described more in determining each video as intensity rank
The mean intensity rank of a image.
4. the system as claimed in claim 1, wherein the processor is additionally configured to execute following steps：
Measurement window is set；And
Step (c) is repeated, until reaching the measurement window.
5. system as claimed in claim 4, wherein the measurement window is based on total total number of images for spending the time or being obtained.
6. system as claimed in claim 4, wherein the measurement window is based on from the calculated slope of step (g).
7. the system as claimed in claim 1, wherein the time interval is based on from the calculated slope of step (g).
8. the system as claimed in claim 1 shows described wherein when being negative value from the calculated slope of step (g)
Colloidal solid dissolves, and when it is positive value, indicate the colloidal solid growth.
9. a kind of system for determining growth/rate of dissolution of colloidal solid, the system comprises：
First light source is configured to the first electromagnetic radiation beam that transmitting is substantially first wave length；
Second light source is configured to the second electromagnetic radiation beam that transmitting is substantially second wave length；
First and second set of beams is synthesized into combination beam, and the combination beam is directed to sample room, the sample
Room is configured to accommodate the colloidal solid and allows the part scattering of the combination beam；
The scattered portion of the combination beam is directed into first sensor and second sensor, wherein first sensing
Device be partial to detection be substantially the first wave length electromagnetic radiation, and the second sensor be partial to detection be substantially
The electromagnetic radiation of second wave length；
It is connected to the processor of first and second sensor, the processor is configured as executing following steps：
A. first and second light source is activated；
B. image is obtained from first and second sensor；
C. step (a) and (b) are repeated at a certain time interval；
D. for each image obtained in step (b), total image intensity levels are determined；
E. to each rank determined in step (d), total image intensity levels are normalized；
F. the formula of the normalized value of digital simulation step (e)；And
G. the slope of the formula of step (f) is calculated.
10. system as claimed in claim 9, wherein the described image in step (b) includes the video for having multiple images.
11. system as claimed in claim 10, wherein the total figure as intensity rank include in determining each video described in
The mean intensity rank of multiple images.
12. system as claimed in claim 9, wherein the processor is additionally configured to execute following steps：
Measurement window is set；And
Step (c) is repeated, until reaching the measurement window.
13. system as claimed in claim 12, wherein the measurement window spends time or the image obtained total based on total
Number.
14. system as claimed in claim 12, wherein the measurement window is based on from the calculated slope of step (g).
15. system as claimed in claim 9, wherein the time interval is based on from the calculated slope of step (g).
16. system as claimed in claim 9, showing described wherein when being negative value from the calculated slope of step (g)
Colloidal solid dissolves, and when it is positive value, indicate the colloidal solid growth.
17. system as claimed in claim 9, further including：
Third light source is configured to the third electromagnetic radiation beam that transmitting is substantially third wavelength, wherein the third radiation
It is combined into the combination beam；
The scattered portion of the combination beam is further directed to 3rd sensor, and the 3rd sensor is partial to examine
Survey the electromagnetic radiation of the substantially second wave length；
The processor is connected to the 3rd sensor, and wherein step (b) further includes being obtained from the 3rd sensor
Image.
18. system as claimed in claim 9, wherein first and second light source is single light source.
19. system as claimed in claim 9, wherein first and second sensor is single-sensor.
20. system as claimed in claim 9, wherein first and second beam is combined by composite structure.
21. system as claimed in claim 9, wherein reaching the first sensor or the second sensor in combination beam
Before, the scattered portion of the combination beam is detached by beam splitter.
22. system as claimed in claim 9, wherein the processor is additionally configured to execute following steps：
Maximum image intensity rank is set；And
If total image intensity levels are more than the maximum intensity rank, the time for exposure of the sensor is adjusted.
23. a kind of method for determining the growth/rate of dissolution of colloidal solid, the method includes：
A. the light source for being configured to emit electromagnetic radiation beam in sample room is provided, the sample room is configured to accommodate the colloid
Particle and the part scattering for allowing the beam；The scattered portion of the beam is directed into sensor, wherein described
Sensor is adapted to detect for the electromagnetic radiation；
B. the light source is activated；
C. image is obtained from the sensor；
D. step (b) and (c) are repeated at a certain time interval；
E. for each image obtained in step (c), total image intensity levels are determined；
E. to each rank determined in step (e), total image intensity levels are normalized；
G. the formula of the normalized value of digital simulation step (f)；And
H. the slope of the formula of step (g) is calculated.
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562241354P | 2015-10-14 | 2015-10-14 | |
| US62/241,354 | 2015-10-14 | ||
| US15/018,532 | 2016-02-08 | ||
| US15/018,532 US9909972B2 (en) | 2016-02-08 | 2016-02-08 | Multi-camera apparatus for observation of microscopic movements and counting of particles in colloids and its calibration |
| US15/194,823 US9541490B1 (en) | 2015-07-01 | 2016-06-28 | Special purpose cuvette assembly and method for optical microscopy of nanoparticles in liquids |
| US15/194,823 | 2016-06-28 | ||
| PCT/US2016/056909 WO2017066487A1 (en) | 2015-10-14 | 2016-10-13 | Apparatus and method for measurements of growth or dissolution kinetics of colloidal particles |
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| JP (1) | JP6887599B2 (en) |
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| WO2017066487A1 (en) | 2017-04-20 |
| CN108369169B (en) | 2021-10-26 |
| JP2018536174A (en) | 2018-12-06 |
| JP6887599B2 (en) | 2021-06-16 |
| WO2017066487A8 (en) | 2018-05-11 |
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