JP6684557B2 - Nanoparticle screening method and screening system - Google Patents

Description

  The present invention relates to a screening method and a screening system capable of efficiently searching for surface modification conditions of nanoparticles.

  Quantum dots (QDs), which are attracting attention as fluorescent substances, have recently been put into practical use as electronic devices and fluorescent labels for living organisms, and vigorous research is still ongoing.

  By the way, quantum dots are rarely used alone, and are often used in combination with other materials such as dispersion in a resin. At this time, in order to improve the dispersibility in other materials, it was necessary to carry out surface modification of the quantum dots accordingly. Patent Document 1 describes polymer-modified metal sulfide nanoparticles that can be easily dispersed in a solution or a resin.

JP, 2006-76831, A

  However, when actually modifying the surface of a quantum dot to obtain effective dispersibility in the dispersion medium, the type and concentration of the surface modifier (surfactant) depending on the dispersion medium, the quantum dot Combinations under various conditions such as concentration occurred, and it took extremely time and labor to search for the conditions.

  In particular, in the case of developed products, the amount of sample that can be used is often small because the manufacturing process is immature and not stable. Therefore, it is difficult to systematically test many surface modification conditions.

  The invention described in Patent Document 1 does not describe a method for searching for conditions for surface modification of quantum dots.

  The present invention has been made in view of such a point, in particular, it is possible to efficiently search the surface modification conditions of the nanoparticles, the time and labor required for surface modification and the amount of sample are reduced from the conventional, An object is to provide a screening method and a screening system for particles.

The method of screening nanoparticles according to the present invention includes a step of subdividing a nanoparticle suspension into each of a plurality of accommodating parts provided in a container, and a surface modification treatment of nanoparticles for each of the accommodating parts. Step, for all the nanoparticle suspension, under the same conditions, the step of incubating at once, adding a dispersion medium in each housing, evaluation of mixing the nanoparticles and the dispersion medium The method has a step of generating a sample, and a step of performing an optical analysis on the evaluation sample of each container, wherein the containers are arranged in a matrix and arranged in one of the rows and columns. With respect to the accommodating portion, while aligning the surface modifying agent, the surface modifying agent is different for the accommodating portion arranged in the other side of the matrix, and for the accommodating portion arranged in the other side of the matrix. , Align the surface modification treatment conditions other than the surface modifier species, with respect to the receiving portion arranged in the one of the matrix, as distinct from the surface modification treatment conditions, and the surface modifier, said surface The reforming conditions are adjusted for each row or each column, and the plurality of light emitting diodes arranged facing the plurality of housings are used as a light source, and the light emitting diodes are arranged facing the plurality of housings. It is characterized in that a plurality of light receiving elements are used as a light receiving section, and the light source and the light receiving element are arranged in the storage container so as to be opposed to each other by a predetermined distance, and the evaluation is performed.

  According to the present invention, the nanoparticle suspension is subdivided into a plurality of storage units, and the nanoparticles in each storage unit are subjected to surface modification treatment under various experimental conditions to perform a plurality of evaluations of different combinations. It is possible to generate samples, and it is possible to perform a series of evaluations on these evaluation samples by optical analysis such as absorbance, fluorescence wavelength and intensity. Therefore, in the present invention, it is possible to study the experimental conditions by using a large number of evaluation samples at one time. Further, the predetermined treatment in the surface modification treatment can be collectively and evenly performed on a large number of evaluation samples divided into the storage containers. As described above, in the present invention, the time required to search for surface modification conditions can be shortened as compared with the related art, and the management of conditions / evaluations can be facilitated and labor can be effectively reduced.

  In the present invention, it is preferable that, at the time of the evaluation, an absorption spectrum and a fluorescence spectrum of the sample in each container are acquired to evaluate the dispersibility and fluorescence characteristics of the nanoparticles.

  Further, in the present invention, it is preferable to inject the nanoparticle suspension in an amount of 20 μL or less into each of 50 or more accommodation parts. In this way, a very small amount of the nanoparticle suspension is put into 50 or more accommodating parts and subjected to the surface modification treatment, so that the nanoparticles can be produced using a small number of nanoparticles, and a large number of evaluation samples can be evaluated. This can effectively reduce the time and cost required for screening.

In the present invention, the container is made of a material having excellent thermal conductivity, the step of incubation is preferably carried out simultaneously for the nanoparticles contained in the respective housing part. In this way, the incubation step can be performed simultaneously for all nanoparticles contained in each housing. Moreover, since the accommodating container has excellent thermal conductivity, it is easy to uniformly transfer heat to the whole, and each nanoparticle can be treated under uniform incubation conditions, and rapid and highly accurate screening can be performed.

  Further, in the present invention, it is preferable to perform vacuum deaeration before the incubation step, during the incubation step, or after the incubation step.

  Further, in the present invention, it is preferable that the accommodating portion constitutes a separable individual container, and the individual container is separated from the accommodating container to enable individual processing. As described above, in the present invention, the accommodation section can be separated from the accommodation container as an individual container, and in accordance with the experimental conditions, the evaluation conditions, etc., a step of processing all the individual containers set in the accommodation container, and individually processing It can be divided into the steps to take. Thereby, nanoparticles can be efficiently screened.

  Further, in the present invention, the accommodating portions are arranged in a matrix, and the surface modifier is aligned with respect to the accommodating portions arranged in one side of the matrix, and the accommodating portions arranged in the other side of the matrix are With different surface modifiers, with respect to the accommodating section arranged in the other side of the matrix, the surface modification treatment conditions other than the surface modifying agent species are aligned, and for the accommodating section arranged in the one side of the matrix. Therefore, it is preferable that the surface modification treatment conditions are different. In this way, by adjusting the surface modifying agent and the surface modifying treatment condition for each row or each column, it becomes easier to manage and the labor can be effectively reduced.

  Further, in the present invention, it is preferable that the plurality of light emitting diodes arranged facing the plurality of housing portions are used as a light source to perform the evaluation. Further, in the present invention, it is preferable that the plurality of light receiving elements arranged so as to face the plurality of accommodating portions are used as a light receiving portion to perform the evaluation. As a result, the evaluation can be performed on a large number of evaluation samples at once, and the time required to search for the surface modification conditions can be effectively shortened as compared with the conventional case.

Further, in the nanoparticle screening system of the present invention, the nanoparticle suspension is subdivided into each of the plurality of accommodating parts provided in the accommodating container, and the surface modification treatment of the nanoparticles is performed for each of the accommodating parts. , All nanoparticle suspensions were incubated at the same time under the same conditions, and a dispersion medium was added to each container to produce an evaluation sample in which the nanoparticles and the dispersion medium were mixed. In the screening system for nanoparticles, wherein the evaluation sample of each container is evaluated by optical analysis, the containers are arranged in a matrix, and the containers arranged in one of the rows and columns. On the other hand, while aligning the surface modifiers, the surface modifiers are different for the accommodating parts arranged in the other side of the matrix, and for the accommodating parts arranged in the other side of the matrix. , Align the surface modification treatment conditions other than the surface modifier species, with respect to the receiving portion arranged in the one of the matrix, as distinct from the surface modification treatment conditions, and the surface modifier, said surface The modification processing conditions are adjusted for each row or each column, and the plurality of light emitting diodes arranged facing the plurality of housings are used as a light source, and are arranged facing the plurality of housings. The evaluation is performed by using a plurality of light-receiving elements as a light-receiving unit, and the light source and the light-receiving element are arranged to face each other in the storage container so as to be separated from each other by a predetermined distance. According to the screening system of the present invention, the time required to search for surface modification conditions can be shortened as compared with the prior art, and the management of conditions / evaluations can be facilitated and labor can be effectively reduced.

  According to the present invention, it is possible to study experimental conditions and the like using a large number of evaluation samples at one time. Further, the predetermined treatment in the surface modification treatment can be collectively and evenly performed on a large number of evaluation samples divided into the storage containers. As described above, in the present invention, it is possible to shorten the time required to search for surface modification conditions by using a smaller amount of sample than in the past, and to easily manage the conditions / evaluations and effectively reduce labor. it can.

It is a flow chart which shows a step of a screening method of nanoparticles in an embodiment of the invention. It is a graph which shows the wavelength of an evaluation sample in experiment-3, and the relationship of light absorbency. It is a graph which shows the relationship between the wavelength and intensity | strength of the evaluation sample in experiment-3.

  Hereinafter, one embodiment of the present invention (hereinafter, abbreviated as “embodiment”) will be described in detail. The present invention is not limited to the following embodiments, and can be variously modified and implemented within the scope of the gist.

  The method of screening nanoparticles according to the present embodiment includes a step of subdividing the nanoparticle suspension into the storage portions of the storage container, a step of subjecting each nanoparticle suspension to a surface modification treatment under different conditions, and a nanoparticle suspension. The method includes a step of obtaining an evaluation sample by dispersing with a dispersion medium, and a step of evaluating the evaluation sample with an absorption spectrum or a fluorescence spectrum.

  For example, in the present embodiment, it is possible to generate a large number of evaluation samples with different surface modification conditions by using a microwell plate having a large number of holes (wells) and perform optical analysis evaluation of these evaluation samples in series. And

  FIG. 1 is a flowchart showing steps of a method for screening nanoparticles according to an embodiment of the present invention.

  In step ST1 shown in FIG. 1, a nanoparticle turbid liquid containing quantum dots (hereinafter referred to as QD liquid) is generated. Quantum dots can be synthesized by mixing a compound as a raw material of constituent elements to generate a precursor solution, and reacting the precursor solution with, for example, a microreactor. The synthesized quantum dots can be subjected to a purification process by a known method. The QD liquid can be obtained by mixing the purified quantum dots with a solvent. The solvent is not limited, and examples thereof include alcohols, ketones, toluene, water and the like.

  Next, in step ST2 shown in FIG. 1, the QD liquid obtained in step ST1 is injected little by little into a large number of storage parts provided in the storage container. As the storage container, for example, a microwell plate in which wells as storage portions are arranged in a matrix can be used. As described above, in the present embodiment, screening can be performed using an existing microwell plate. Alternatively, it is possible to use a plate-shaped storage container in which a large number of individual containers whose well portions can be removed are arranged. It does not matter what the material of the container is, but glass is preferable. In particular, it is preferable that the container is made of a material having more excellent heat resistance and chemical resistance than that of plastic by the incubation step. Further, it is desirable that the container is covered with a cap or a film in order to prevent evaporation of the solvent during the incubation and in the optical analysis. In particular, a cover coated with Teflon (registered trademark) is used as a cover during the optical analysis to prevent the solvent from eroding the cover to cause whitening and reduce the analysis accuracy. Further, by using a material having excellent thermal conductivity for the storage container, it is possible to apply substantially even heating to each QD liquid subdivided into each storage portion. Therefore, variations in heating temperature can be suppressed, and highly accurate evaluation can be performed on each evaluation sample.

  Although the number of accommodating portions arranged in the accommodating container is not limited, specifically, it is preferably 50 or more, more preferably 96 or more, and further preferably 150 or more. The volume of each accommodation portion is, for example, 3.0 mL or less, preferably 1.5 mL or less. Further, since the viscosity of the monomer serving as the dispersion medium is generally high, it is difficult to stir when the sample amount is too small. For this reason, it is desirable that the volume of the accommodating portion is 0.5 mL or more, preferably 1.0 mL or more. In an experiment described later, a microwell plate having 96 glass wells in a plate holder made of plastic or aluminum was used.

  Further, the QD concentration to be injected into each container can be calculated from the QD concentration actually desired to be obtained in the matrix and the addition amount to be added to each container. Specifically, the QD concentration is preferably 0.1% or more, more preferably 1% or more, still more preferably 10% or more. The QD liquid volume is several tens of μL or less (specifically 50 μL or less), preferably 20 μL or less, more preferably 10 μL or less, and further preferably 5 μL or less. In the present embodiment, the quantity of QD solution added to each of a plurality of, preferably 50 or more, accommodating parts is set to several tens of μL or less, preferably 20 μL or less, so that the QD solution used in one accommodation container is As a whole, it can be suppressed to several mL or less, and the amount of reagent per condition is about 1/10 to 1/100 as compared with the conventional one. Therefore, it is particularly effective in searching for the surface treatment conditions of the developed product whose quality is not stable. In addition, since many quantum dots and surface modifiers are expensive, it is possible to suppress the amount of reagents used per one experiment using a container, which is also effective in terms of cost.

  Subsequently, in the present embodiment, a surface modification process is performed in step ST3 of FIG. At this time, a different type of surface modifier is added to each QD solution. For example, in Experiment-1 described later, eight kinds of surface modifiers (surfactants) are used.

  In this embodiment, the surface modification conditions can be made different by the following factors. For example, (1) modifier species (2) surface modifier concentration (3) solvent concentration during surface modification treatment (4) incubation time, etc.

  As shown in FIG. 1, in the surface modification treatment, a surface modifying agent and a solvent are added under different conditions (step ST3-1), followed by incubation (step ST3-2).

  The surface modifier can be added in two or more stages, as in Experiment 2 and Experiment 3 described later. Further, the solvent of the surface modifier may not be used (that is, the surface modifier is directly added to the QD liquid). Further, it is preferable to use a solvent such as toluene in which the quantum dots are dispersed and the surface modifier is dissolved, as the solvent.

  By this step ST3, the surface modification treatment can be performed on the QD liquid stored in each storage portion under different conditions.

  The incubation can be performed using an oven or an incubator. In the incubation, the temperature and the time are adjusted, but in the present embodiment, the incubation can be performed at once under the same conditions for all the QD liquids contained in each container. During the incubation, it is desirable to stir the solution using a shaker, a magnetic stirrer, or a fine stirring rod in order to avoid segregation of the surface modifier due to QD aggregation.

  Further, it is desirable to apply ultrasonic dispersion because the aggregated state can be relaxed in a shorter time and the homogeneity of the solution in the well is improved. Furthermore, if necessary, different incubation temperature conditions can be applied, for example, by incubating samples prepared under the same conditions on a hot plate having a temperature gradient.

  After the addition of the surface modifier and the solvent and before the incubation, the shaking treatment, stirring, ultrasonic treatment and the like may be performed. In this case, heating the sample to 40-100 ° C. lowers the viscosity of the medium and facilitates stirring and the like. Vacuum degassing may be performed before, during, or after incubation to remove low-boiling impurities such as water and volatile contaminants, as well as the dispersion medium (toluene, etc.) used for the nanoparticle suspension. It is also possible to do so. Also in this case, it is easier to remove the solvent by heating if necessary.

  Next, in step ST4 shown in FIG. 1, an aggregating agent is added after the incubation. The aggregating agent is not particularly limited as long as it is a solvent having a polarity different from the surface polarity of the quantum dots. For example, when the quantum dots and the surface modifier are dispersed in a chlorofluorocarbon solvent, toluene serves as an aggregating agent. Alternatively, an alcohol such as ethanol can be a flocculant.

  Next, in step ST5 shown in FIG. 1, the quantum dots are filtered or settled to remove the supernatant liquid. This makes it possible to obtain surface-modified quantum dots. For example, it is possible to move to step ST5 after repeating the addition of the aggregating agent and the centrifugal separation. At this time, the aggregating agents used in the repeating step may be the same type or different types. It should be noted that whether or not step ST4 and step ST5 are performed can be arbitrarily determined.

  Next, in step ST6 shown in FIG. 1, the surface-modified quantum dots housed in each housing unit and the dispersion medium are mixed to generate an evaluation sample. For the mixing, for example, a shaker for microplate can be used. In the present embodiment, mixing can be performed on each evaluation sample at the same time. As described above, in this embodiment, a large number of evaluation samples having different surface modification conditions can be generated at one time.

  Next, in step ST7 shown in FIG. 1, optical analysis evaluation is performed on each evaluation sample. The evaluation can be performed mainly by an absorptiometric method and a fluorescence analysis method. This makes it possible to evaluate the dispersibility and fluorescence characteristics of the quantum dots. As an absorptiometric method or a fluorescence analysis method, if an absorption spectrum or a fluorescence spectrum can be obtained, the degree of dissolution or its rate, the cause of fluorescence deactivation (dissolution or, Other than that), it is more desirable because it is possible to simultaneously know the information such as the dissolution of the additive, the interaction with QD, and the speed thereof.

  It can be evaluated by focusing on the absorption and absorption obtained by the fluorometric method. That is, when the aggregation of the quantum dots is large, the light scattering is large, so that the transmittance is reduced. Therefore, for example, when measuring an absorption spectrum, the baseline rises. Further, in the case of measuring an absorption spectrum, the position of the absorption peak is related to the particle diameter, and when the peak disappears, it means that the quantum dot is dissolved or phase-separated and disappears from the optical path.

  On the other hand, when an LED is used as a light source, the condition that the absorbance (the sum of the absorbance of the QD itself and the absorbance of the target dispersion medium) originally possessed by the sample itself does not increase by 0.1 or more from the absorbance at a wavelength of 0.1 or less In addition, dispersibility can be evaluated. Further, it can be evaluated that the QD disappears and there is no phase separation on the condition that the absorbance at the excitation wavelength does not significantly decrease (specifically, it does not decrease by 10% or more). The baseline and peak extinction can be evaluated by comparing with a reference evaluation sample (reference sample). For example, the reference sample may be a quantum dot dispersed in a good solvent such as toluene before the surface modification treatment.

  Further, as the absorbance, when there are many wavelengths at which the above-mentioned inherent absorbance of the sample itself is 0.1 or less, the shortest possible wavelength is desirable because the scattering intensity is high. In particular, it can be evaluated under the condition that the absorbance in visible light having a wavelength of 720 nm or less is 0.1 or less.

  Further, in the fluorescence intensity obtained by the fluorometric method, when the fluorescence intensity is lower than the fluorescence intensity of the reference sample listed above, in the case of the same degree, and when it is increased, or when compared with the reference sample Can be evaluated by the rate of decrease and the rate of increase in the fluorescence intensity.

  In optical analysis during evaluation, high-speed measurement is possible, so quick evaluation is possible for each evaluation sample, and the time required for the characteristic evaluation of many evaluation samples stored in the container is conventionally reduced. It can be shortened compared to.

  In addition, in the present embodiment, the above-described evaluation can be performed by using a plurality of light emitting diodes arranged facing a plurality of accommodating portions as a light source. In addition, in the present embodiment, it is possible to perform measurement while moving each sample between one light receiver and a light emitting diode, but it is possible to receive light from a plurality of light receiving elements arranged facing a plurality of accommodating portions. It can be used as a part to perform the above-mentioned evaluation. As described above, it is more preferable to perform the above-described optical analysis evaluation in a state in which the light emitting diode and the light receiving portion are separated from each other by a predetermined distance and face each other so as to sandwich the container of the present embodiment from above and below. As a result, the optical analysis evaluation can be performed on a large number of evaluation samples at once, and the time required to search for surface modification conditions can be more effectively shortened as compared with the conventional case.

  A monochromatic light emitting diode may be used as the light emitting diode, and a two-color LED (multicolor LED if necessary) and an optical filter should be used together as long as there is no overlap in the spectrum of the light emitted from the light emitting diode. You can At this time, it is possible to reduce the space and the amount of the reagent as a structure in which only the light having the wavelength required for the dispersibility evaluation or the dissolution and the fluorescence intensity evaluation is detected by the light receiving section.

  Furthermore, by performing optical analysis continuously over a long period of time, temporal changes in absorbance and fluorescence intensity can be captured, so that temporal stability of the sample itself can be confirmed.

  A white light source such as a xenon lamp can also be used as the light source for optical analysis used in the present embodiment, but as described above, a plurality of light emitting diodes arranged facing the plurality of accommodating portions. Is preferably used as a light source for evaluation. The wavelength of the light emitting diode in the case of the absorbance evaluation is a wavelength at which the absorbance of the nanoparticles and the medium in which the nanoparticles are dispersed is 0.1 or less (for example, in the case of QD that emits visible light, the green light emitting particles are used). In the case of, and 700 nm in the case of red light-emitting particles). Further, when it is desired to investigate the dissolution of particles and the separation of solvent, it is desirable to use fluorescent nanoparticles that absorb and have the same wavelength as the excitation light source for fluorescence described later.

  In the case of fluorescence evaluation, the wavelength should be such that nanoparticles are efficiently and appropriately excited (for example, 350 nm, 365 nm, 375 nm, 385 nm, 395 nm, 400 nm, 405 nm, 410 nm, 420 nm, 430 nm, 440 nm, 450 nm, 460 nm). Is desirable. The light-emitting diode for absorbance evaluation and the light-emitting diode for fluorescence evaluation may be used in combination, or may be appropriately replaced when used. Further, in the present embodiment, it is possible to obtain a spectrum of fluorescence and transmitted light by using a diffraction grating or the like and analyze it, but as described above, they are arranged so as to face a plurality of accommodating portions. It is preferable to perform evaluation by using a plurality of light receiving elements as a light receiving unit. In the case of fluorescence evaluation, it is preferable to insert an optical filter for blocking the light emitting element between the light emitting element and the light receiving element in order to block the incident light from the light emitting element. As a result, the evaluation can be performed on a large number of evaluation samples at once, and the time required to search for the surface modification conditions can be effectively shortened as compared with the conventional case.

  As described above, according to the present embodiment, the nanoparticle suspension is subdivided into a plurality of accommodating portions, and the nanoparticles in each accommodating portion are subjected to the surface modification treatment under various experimental conditions to change the conditions. It is possible to create a plurality of evaluation samples in combination, and it is possible to perform a series of optical analysis evaluations for these evaluation samples. Therefore, in the present embodiment, it is possible to study the surface modification conditions and the like by using a large number of evaluation samples at one time. Further, the predetermined treatment in the surface modification treatment can be collectively and evenly performed on a large number of evaluation samples divided into the storage containers. As described above, in the present embodiment, the time required to search for surface modification conditions can be shortened as compared with the conventional one, the amount of samples and reagents can be reduced, and further, the management of conditions / evaluations can be facilitated and labor can be effectively saved. Can be reduced to

  In the present embodiment, the above-mentioned nanoparticle screening method can be presented as a screening system. That is, the screening system in the present embodiment, each of the plurality of storage units provided in the storage container, the nanoparticle suspension is subdivided, the surface modification treatment of the nanoparticles under different conditions for each storage unit. That is, the dispersion medium is added to each accommodation unit to generate an evaluation sample in which the nanoparticles and the dispersion medium are mixed, and the evaluation sample in each accommodation unit is evaluated by optical analysis. Is characterized by.

  Then, the following experiment was specifically tried using the nanoparticle screening method shown in FIG.

[Experiment on Surface Modification Agent for Dispersion in Freon Solvent-1]
Considering the dispersibility of CdSe-based quantum dots used as an LED sealing material in hexafluorometa-xylene, the surface modification conditions of CdSe-based quantum dots were investigated.

  First, in step ST1 of FIG. 1, a nanoparticle suspension liquid (QD liquid) containing CdSe-based quantum dots was generated.

  For example, each compound as a raw material for the Cd source and the Se source was dissolved to produce a CdSe-based precursor solution. Then, the CdSe-based precursor solution was reacted using a microreactor to synthesize CdSe-based quantum dots.

  Subsequently, the surface of the CdSe-based quantum dot was coated with each shell of ZnS and ZnSe. For example, the dot surface was coated with a first shell portion made of ZnSe synthesized by reacting raw materials prepared by mixing a Zn source and an Se source by a continuous injection method. Subsequently, the surface of the first shell portion was coated with a second shell portion made of ZnS synthesized by reacting a ZnS raw material by a continuous injection method. The toluene dispersion of CdSe-based quantum dots having the core / shell structure thus generated was injected into each well of a glass microwell plate (capacity 1.5 mL × 96 wells) by a predetermined amount (tens of μL). (Step ST2). CdSe-based quantum dots have the same concentration in all wells.

Next, a surface modification treatment was performed on each CdSe-based quantum dot (step ST3). Here, the surface modification species used were fluorobenzene thiol two _{(C 6 H 4 F-SH} , C 6 F 5 -SH), fluoroalkane alcohol one _{((C 6 F 13) (} C 2 H ₄ ) OH), one type of perfluorocarboxylic acid type ((C ₇ F ₁₅ ) COOH), one type of fluoroalkanethiol type ((C ₈ F ₁₇ ) (C ₂ H ₄ ) SH), fluoroalkane amine type 2 Kind ((C ₈ F ₁₇ ) (C ₃ H ₆ ) NH ₂ , (C ₇ F ₁₅ ) (CH ₂ ) NH ₂ ), 1 kind of fluoroalkane ester type ((C ₆ F ₁₃ ) (C ₂ H ₄ ). A total of eight types of OCOC (CH ₂ ) CH ₃ ) were used. Further, the concentration of the surface modifier is set to 5%, 10%, and 20%. Further, the toluene concentration during the surface modification treatment was set to 3%, 10%, and 20%. All the concentrations are% by mass. Hexafluoromethaxylene was used as the solvent for the surface modifier.

  Next, incubation was performed. The incubation temperature at this time was set to 40 ° C. The incubation time was 3 hours or 24 hours.

  Subsequently, toluene was added as a flocculant (step ST4), and the mixture was flocculated / precipitated to remove the supernatant (step ST5).

  The surface-modified CdSe-based quantum dots thus obtained were mixed with hexafluoromethaxylene as a dispersion medium to obtain an evaluation sample (step ST6).

  Then, using a microplate reader, visible-ultraviolet absorption spectroscopic analysis and fluorescence spectroscopic analysis were performed to evaluate the dispersibility and fluorescence characteristics of the quantum dots.

  In the above experiment, since the quantum dot concentration was adjusted to be the same under each experimental condition at the time of sample preparation, the evaluation samples can be compared with each other.

  In this experiment, toluene-dispersed quantum dots (no surface modification treatment) was used as a reference sample, and each evaluation sample was relatively evaluated with respect to the reference sample.

  First, the baseline and the absorption peak were investigated from the absorption spectrum obtained by visible-ultraviolet absorption spectroscopy. Table 1 below shows the evaluation results of the dispersibility of each evaluation sample when the incubation time was 3 hours. Table 2 shows the evaluation results of the dispersibility of each evaluation sample with the incubation time of 24 hours.

  The vertical axis of Table 1 and Table 2 shows the type of the surface modifier added, and the upper row of the horizontal axis shows the toluene concentration during the surface modification treatment (toluene 0%, toluene 3%, toluene 10%). And toluene 30%) are shaken. The numerical values of 5%, 10% and 20% shown on the lower side of the horizontal axis indicate the concentration of the surface modifier.

  The triangles shown in Tables 1 and 2 indicate that the baseline was higher than that of the reference sample. The increase in the baseline indicates that the quantum dots are not well dispersed in the dispersion medium and are in an aggregated state.

  Further, x shown in Tables 1 and 2 indicates a state in which the quantum dots are dissolved or the peak disappears due to segregation of the quantum dots due to phase separation and vigorous aggregation.

  On the other hand, ◯ shown in Tables 1 and 2 indicates an evaluation sample whose baseline is equal to or less than that of the reference sample and whose absorption peak is equal to or more than that of the reference sample.

  As shown in Table 1 and Table 2, by adjusting the toluene concentration and the concentration of the surface modifying agent for all of the eight types of surface modifying agents, the dispersion medium was maintained while maintaining the absorption spectrum of the reference sample or higher. We have found conditions that allow proper dispersion in hexafluorometa-xylene.

  Further, it is preferable to set the incubation time within 24 hours according to the experimental results shown in Table 1 and Table 2. Further, even if the incubation time is set to about 3 hours, it is more preferable to set the incubation time to 3 hours or less in order to shorten the evaluation time because the preferable dispersibility is obtained.

  Next, the fluorescence intensity was examined from the fluorescence spectrum obtained by the fluorescence spectroscopic analysis. Table 3 below shows the evaluation results of the fluorescence characteristics of each evaluation sample when the incubation time was 3 hours. Table 4 shows the evaluation results of the fluorescence intensity of each evaluation sample when the incubation time was 24 hours.

  The vertical axis of Tables 3 and 4 shows the type of the surface modifier added, and the upper row of the horizontal axis shows the toluene concentration during the surface modification treatment (toluene 0%, toluene 3%, toluene 10%). And toluene 30%) are shaken. The numerical values of 5%, 10% and 20% shown on the lower side of the horizontal axis indicate the concentration of the surface modifier.

  The triangles shown in Tables 3 and 4 indicate the same fluorescence intensity as that of the reference sample. Further, x shown in Tables 3 and 4 indicates that the fluorescence intensity is lower than that of the reference sample. Further, ◯ shown in Tables 3 and 4 indicates that the fluorescence intensity is higher than that of the reference sample.

As shown in Tables 3 and 4, pentafluorobenzenethiol (C ₆ F ₅ —SH) and 4,4,5,5,6,6,7,7,8,8,9,9,10, It was found that none of 10,10-heptadecafluoroundecylamine ((C ₈ F ₁₇ ) (C ₃ H ₆ ) NH ₂ ) emitted light.

Further, as shown in Tables 1 to 4, fluorobenzenethiol (C ₆ H ₄ F-SH) had a toluene concentration of 30% regardless of the incubation time of 3 hours and 24 hours, and had a surface modifier. It was found that the dispersibility and the fluorescence intensity were excellent under the condition that the concentration was 5% to 20%.

Further, as shown in Tables 1 to 4, 3,3,4,4,5,5,6,6,7,7,8,8-tridecafluoro-1-octanol ((C ₆ F ₁₃ ). (C ₂ H ₄ ) OH) has dispersibility and fluorescence intensity depending on the conditions that the toluene concentration is 30% and the surface modifier concentration is 5% to 20% regardless of the incubation time of 3 hours and 24 hours. It turned out to be excellent.

In addition, as shown in Tables 1 to 4, perfluorooctanoic acid ((C ₇ F ₁₅ ) COOH) had a toluene concentration of 30% regardless of the incubation time of 3 hours and 24 hours, and the surface modification was performed. It was found that the dispersibility and the fluorescence intensity were excellent when the agent concentration was 5%.

Further, as shown in Tables 1 to 4, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoro- 1-decanethiol ((C ₈ F ₁₇ ) (C ₂ H ₄ ) SH) has a toluene concentration of 30% and a surface modifier concentration of 5% regardless of the incubation time of 3 hours and 24 hours. It was found that the dispersibility and the fluorescence intensity were excellent depending on the conditions.

In addition, as shown in Tables 1 and 3, 2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-pentadecafluorooctylamine ((C ₇ F ₁₅ ) (CH ₂ ) NH ₂ ) has a toluene concentration of 3% and a surface modifier concentration of 5% or 10% regardless of the incubation time of 3 hours or 24 hours, or Dispersibility and fluorescence intensity depending on the condition that the toluene concentration is 10% and the surface modifier concentration is 10% and 20%, or that the toluene concentration is 30% and the surface modifier concentration is 20%. It turned out to be excellent.

As described above, when pentadecafluorooctylamine ((C ₇ F ₁₅ ) (CH ₂ ) NH ₂ ) is used, the surface modification is performed in a wide range from a low toluene concentration of about 3% to a toluene concentration of about 30%. It was found that by adjusting the concentration of the substance in the range of about 5% to 20%, it was possible to uniformly disperse in the fluorine-based solvent and obtain a strong fluorescence intensity.

Moreover, as shown in Table 1 and Table 3, 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl propionate ((C ₆ F ₁₃ ) (C ₂ H ₄ ) OCOC (CH ₂ ) CH ₃ ) has a toluene concentration of 3% when the incubation time is 3 hours and the surface modifier concentration is 10%, or the toluene concentration is The dispersibility and the fluorescence intensity are 10% and the surface modifier concentration is 5% and 10%, or the toluene concentration is 30% and the surface modifier concentration is 5% to 20%. It turned out to be excellent.

In addition, as shown in Tables 2 and 4, 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl propionate ((C ₆ F ₁₃ ) (C ₂ H ₄ ) OCOC (CH ₂ ) CH ₃ ) has a toluene concentration of 0%, a surface modifier concentration of 10%, or a toluene concentration of 3%. The agent concentration is 10%, or the toluene concentration is 10%, and the surface modifier concentration is 5%, 10%, or the toluene concentration is 30%, and the surface modifier concentration is It was found that the dispersibility and the fluorescence intensity were excellent under the condition of 5% to 20%.

  The time required for the above experiment and examination was a little over one day, and about 100 conditions could be searched. Further, similarly to the above-described experimental method, the quantum dots dispersed in the fluorine-based solvent were used to further investigate the dispersion of the quantum dots in the fluorine-based polymer. Then, it was possible to find a condition in which the quantum dots can be dispersed in the fluoropolymer while maintaining good fluorescence intensity without aggregation.

  By the way, 96 wells (holes) are arranged in a matrix in the microwell plate used in the above experiment. Therefore, in the experiment, the same surface modifier was injected into the wells arranged in the matrix row direction (horizontal direction), and different surface modifiers were injected into the wells arranged in the column direction (vertical direction). That is, each of the masses indicated by ◯ Δ in Tables 1 to 4 represents each well, and as shown in Tables 1 to 4, each of the masses arranged in the lateral direction has the same surface modifier. The experimental results in Table 1 are shown, and each of the masses arranged in the vertical direction shows the experimental results with eight different types of surface modifiers.

  In addition, in the experiment, wells lined up in the matrix column direction (vertical direction) were aligned under the same surface modification conditions (other than the surface modifier type), and wells lined up in the row direction (horizontal direction) were surface modified. The conditions (other than the type of surface modifier) were different. That is, as shown in Tables 1 to 4, each mass arranged in the vertical direction shows the experimental result under the same surface modification condition (other than the surface modifier type), and each mass arranged in the horizontal direction has a different surface. The experimental results under modifying conditions (other than the type of surface modifier) are shown.

  In this way, by adjusting the surface modifying agent and the surface modifying conditions for each row or each column, it becomes easy to manage and the labor can be effectively reduced.

[Experiment on Surface Modification Agent for Dispersion in Freon Solvent-2]
3 mL of the CdSe-based quantum dot stock solution produced in the above Experiment-1 was washed with ethanol, and the QD solution mixed with 100 μL of toluene was used to produce the following evaluation sample.

(Evaluation sample-1)
The QD solution is subdivided into 10 μL each and injected into a plurality of storage parts, and then 50 μL of solvent, 5 μL of decanethiol (fluoroalkaneamine type), and 1 μL of undecylamine (fluoroalkaneamine) are added in this order, and Vortex is added. After dispersing with a mixer, it was filtered. Subsequently, 50 μL of the fluororesin solution was mixed and dried.

(Evaluation sample-2)
The QD solution was divided into 10 μL aliquots and injected into a plurality of containers, and then 5 μL of decanethiol, 1 μL of undecylamine, and 50 μL of solvent were added in this order, and the mixture was dispersed with a Vortex mixer and then filtered. Subsequently, 50 μL of the fluororesin solution was mixed and dried.

  As the solvent put in each evaluation sample, three types of Novec (registered trademark) 7200 (A), FC72 / Novec 7200 (addition ratio = 1/1) (B), and FC72 (C) were used.

Then, the absorbance, fluorescence peak, fluorescence area, area / absorbance, and toluene dispersion ratio of each evaluation sample were obtained. The FC 72 is C ₆ F ₁₄ . The experimental results are shown in Table 5 below.

  The toluene dispersion shown in Table 5 is a QD liquid that has not been surface-modified. "1" of "1-A" shown in the column of Table 5 shows the evaluation sample-1 and "A" shows Novec 7200 (A) which is a solvent. The other column notations are shown accordingly.

  As shown in Table 5, in the evaluation sample-2 in which decanethiol was added before undecylamine and then dispersed in the solvent, the absorbance can be lowered and the fluorescence peak can be reduced as compared with the evaluation sample-1. It turned out that it can be made equal.

  In this way, by using two types of surface modifiers, decanethiol and undecylamine, together and adjusting the order of addition, quantum dots (surfaces) with good dispersibility in fluororesin and with toluene dispersion can be obtained. Surface modification conditions with high fluorescence intensity could be easily and speedily obtained by the screening method of the present invention, compared to the case (without addition of a modifier).

[Experiment on Surface Modification Agent for Dispersion in Freon Solvent-3]
2.4 mL of the CdSe-based quantum dot stock solution produced in the above Experiment-1 was washed with 7.2 mL of ethanol for the first time and then with 3.2 mL of ethanol for the second time, and then to 60 μL of toluene. The following evaluation samples were generated using the QD liquid obtained by mixing.

(Evaluation sample-3)
The QD solution is subdivided into 50 μL each and injected into a plurality of containers. Then, 5 μL of decanethiol, 1 μL of undecylamine, and C ₆ F ₁₄ (250 μL) (D) as a solvent are added in this order, and Vortex is added. After dispersing with a mixer and centrifugation to separate the layers, the lower layer was extracted and filtered. Then, it was mixed with 250 μL of the fluororesin solution and then dried.

(Evaluation sample-4)
The QD solution was divided into 10 μL aliquots and injected into a plurality of containers, and then 5 μL of decanethiol, 2 μL of undecylamine, and (C ₃ F ₇ ) ₃ N (50 μL) (E) in that order. The mixture was put in, dispersed by a Vortex mixer, centrifuged to separate the layers, and then the lower layer was extracted and filtered. Then, it was mixed with 250 μL of the fluororesin solution and then dried.

  Then, the absorbance, the absorption peak, the fluorescence peak, the fluorescence area, and the area / absorbance of each evaluation sample were obtained. The experimental results are shown in Table 6 below.

  The notations 3, 4 shown in Table 6 indicate the numbers of the evaluation samples. FIG. 2 is a graph showing the relationship between the wavelength and the absorbance of the evaluation sample in Experiment-3. Further, FIG. 3 is a graph showing the relationship between the wavelength and the intensity of the evaluation sample in Experiment-3.

Experiments more as a solvent for (C 3 _{F 7)} 3 Evaluation Sample -4 with _N is, the evaluation sample -3 large can high strength fluorescent area compared to, also been found that strength reduction after drying is less .

  Thus, by using two kinds of surface modifiers, decanethiol and undecylamine, together and adjusting the solvent, the surface modification with good dispersibility in the fluororesin and high fluorescence intensity is achieved. The conditions could be obtained easily and speedily by the screening method of the present embodiment.

  According to the nanoparticle screening method and screening system of the present invention, the time required to search for surface modification conditions can be shortened as compared with the prior art, and the management of conditions / evaluations is facilitated and labor is effectively reduced. be able to. Therefore, it is possible to search for an appropriate surface modification condition when combining nanoparticles with a polymer or the like.

Claims (7)

In each of the plurality of storage units provided in the storage container, a step of subdividing the nanoparticle suspension,
A step of performing a surface modification treatment of the nanoparticles for each of the accommodating parts,
Incubating all the nanoparticle suspensions under the same conditions at once,
Adding a dispersion medium in each accommodation part, and generating an evaluation sample in which the nanoparticles and the dispersion medium are mixed,
A step of performing an optical analysis on the evaluation sample of each container,
Have
The accommodating portions are arranged in a matrix, and the surface modifying agent is aligned with the accommodating portions arranged in one side of the matrix, and the surface modifying agent is arranged with respect to the accommodating portions arranged in the other side of the matrix. Different from each other, with respect to the accommodating portions arranged in the other side of the matrix, the surface modification treatment conditions other than the surface modifying agent species are aligned, and the surface of the accommodating portions arranged in the one side of the matrix is the surface. Assuming that the modification processing conditions are different,
The surface modifier and the surface modification treatment conditions are adjusted row by row or column by column,
Utilizing a plurality of light emitting diodes arranged facing the plurality of housing portions as a light source, using a plurality of light receiving elements arranged facing the plurality of housing portions as a light receiving portion,
A method for screening nanoparticles, wherein the light source and the light receiving element are placed in the storage container so as to be separated from each other by a predetermined distance and face each other, and the evaluation is performed.   The nanoparticle screening method according to claim 1, wherein, in the evaluation, an absorption spectrum and a fluorescence spectrum of the sample in each accommodation unit are acquired, and dispersibility and fluorescence characteristics of the nanoparticles are evaluated. .   The nanoparticle screening method according to claim 1 or 2, wherein the nanoparticle suspension is injected in an amount of 20 µL or less into each of 50 or more accommodation units. The container is formed of a material having excellent thermal conductivity, the step of incubation, any of claims 1 to 3, which comprises carrying out simultaneously for the nanoparticles contained in the respective housing part 7. The method for screening nanoparticles according to.   The method for screening nanoparticles according to any one of claims 1 to 4, wherein vacuum deaeration is performed before the step of incubation, during the step of incubation, or after the step of incubation.   6. The nano according to claim 1, wherein the accommodating portion constitutes a separable individual container, and the individual container is separated from the accommodating container to enable individual processing. Particle screening method. In each of the plurality of storage units provided in the storage container, the nanoparticle suspension is subdivided, the surface modification treatment of nanoparticles is performed for each storage unit, for all nanoparticle suspension Under the same conditions, incubation is performed at one time, a dispersion medium is added to each accommodation unit, an evaluation sample in which the nanoparticles and the dispersion medium are mixed is generated, and for each evaluation sample in each accommodation unit, And a screening system for nanoparticles evaluated by optical analysis,
The accommodating portions are arranged in a matrix, and the surface modifying agent is aligned with the accommodating portions arranged in one side of the matrix, and the surface modifying agent is arranged with respect to the accommodating portions arranged in the other side of the matrix. Different from each other, with respect to the accommodating portions arranged in the other side of the matrix, the surface modification treatment conditions other than the surface modifying agent species are aligned, and the surface of the accommodating portions arranged in the one side of the matrix is the surface. The surface modification agent and the surface modification treatment conditions are adjusted row by row or column by column, with different modification treatment conditions.
The plurality of light emitting diodes arranged facing the plurality of housing portions are used as a light source, and the plurality of light receiving elements arranged facing the plurality of housing portions are used as a light receiving portion. A nanoparticle screening system, characterized in that an element and a container are placed in the storage container so as to be separated from each other by a predetermined distance and face each other, and the evaluation is performed.

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