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Publication numberUS20020083888 A1
Publication typeApplication
Application numberUS 09/751,670
Publication dateJul 4, 2002
Filing dateDec 28, 2000
Priority dateDec 28, 2000
Also published asUS6682596, US7144458, US20020144644, US20040247517, WO2002053810A1
Publication number09751670, 751670, US 2002/0083888 A1, US 2002/083888 A1, US 20020083888 A1, US 20020083888A1, US 2002083888 A1, US 2002083888A1, US-A1-20020083888, US-A1-2002083888, US2002/0083888A1, US2002/083888A1, US20020083888 A1, US20020083888A1, US2002083888 A1, US2002083888A1
InventorsDonald Zehnder, Marcel Bruchez, Joseph Treadway
Original AssigneeZehnder Donald A., Bruchez Marcel P., Treadway Joseph A.
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Flow synthesis of quantum dot nanocrystals
US 20020083888 A1
Abstract
Nanocrystals are synthesized with a high degree of control and hence product quality control in a flow-through reactor in which the reaction conditions are maintained by on-line detection of characteristic properties of the product and by adjusting the reaction conditions accordingly. The coating of nanocrystals is achieved in an analogous manner.
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Claims(44)
What is claimed is:
1. A process for the preparation of monodisperse luminescent semiconductor nanocrystals having detectable properties within a target range, said method comprising:
(a) combining nanocrystal-forming reactants with a solvent to form a solution;
(b) continuously passing said solution at a selected flow rate through a thermally conductive reaction tube embedded in a heat transfer medium maintained at a temperature sufficiently high to initiate a reaction among said reactants, thereby producing a product mixture containing nanocrystals;
(c) monitoring said product mixture to detect properties of said nanocrystals that are indicative of the degree to which said nanocrystals possess desired characteristics; and
(d) comparing the value of said properties thus detected with said target range and adjusting either the temperature of said heat transfer medium, the flow rate of said solution, or both, if needed to correct any deviation between said value of said detected properties and said target range.
2. A process in accordance with claim 1 in which said properties thus detected are optical properties.
3. A process in accordance with claim 1 further comprising cooling said product mixture between steps (b) and (c) to a temperature sufficiently low to quench said reaction.
4. A process in accordance with claim 1 in which step (c) is performed upon emergence of said product mixture from said reaction tube.
5. A process in accordance with claim 3 in which said cooling is performed by combining additional solvent with said product mixture, said additional solvent being at a temperature and a proportion relative to said product mixture sufficient to achieve a final temperature sufficiently low to quench said reaction.
6. A process in accordance with claim 2 in which said optical features are photoluminescent emission spectra, and step (c) comprises irradiating said product mixture with light and detecting wavelength spectra of photoluminescent energy emitted from said nanocrystals.
7. A process in accordance with claim 2 in which said optical features are absorbance, and step (c) comprises irradiating said product mixture with light and detecting absorbance spectra of said nanocrystals.
8. A process in accordance with claim 2 in which said optical features are light scattering, and step (c) comprises irradiating said product mixture with light and detecting the presence of light scattering by said nanocrystals.
9. A process in accordance with claim 1 in which said thermally conductive reaction tube is a coiled tube cast in a solid block of heat conductive metal.
10. A process in accordance with claim 1 in which said heat transfer medium of step (b) is maintained at a temperature of at least about 100° C.
11. A process in accordance with claim 1 in which said heat transfer medium of step (b) is maintained at a temperature of from about 100° C. to about 400° C.
12. A process in accordance with claim 1 in which said nanocrystal-forming reactants are (i) a member selected from the group consisting of an organocadmium compound and an organozinc compound and (ii) a member selected from the group consisting of an elemental chalcogen and a chalcogen-containing compound.
13. A process in accordance with claim 12 in which said chalcogen is a member selected from the group consisting of sulfur, selenium, and tellurium.
14. A process in accordance with claim 12 in which said chalcogen is selenium.
15. A process in accordance with claim 1 in which said nanocrystal comprises a member selected from the group consisting of CdSe, CdS, CdTe, and ZnSe.
16. A process in accordance with claim 1 in which said coordinating solvent is a member selected from the group consisting of alkyl phosphines, alkyl phosphine oxides, pyridines, furans, ethers, amines, and alcohols.
17. A process in accordance with claim 1 in which said solvent is a member selected from the group consisting of tri-n-octylphosphine and tri-n-octylphosphine oxide.
18. A process in accordance with claim 1 in which said solvent is a mixture of tri-n-octylphosphine and tri-n-octylphosphine oxide.
19. A process in accordance with claim 1 in which step (d) comprises adjusting the temperature of said heat transfer medium.
20. A process in accordance with claim 1 in which step (d) comprises adjusting the flow rate of said solution.
21. A process for the coating of nanocrystals with a passivating coating to achieve coated nanocrystals having detectable properties within a target range, said method comprising:
(a) combining nanocrystal cores with surface passivating reactants and a coordinating solvent to form a dispersion;
(b) continuously passing said dispersion through a thermally conductive reaction tube embedded in a heat transfer medium maintained at a temperature sufficiently high to initiate a reaction among said passivating reactants, thereby producing a product mixture containing nanocrystals coated with a passivating coating;
(c) monitoring said product mixture to detect properties of said nanocrystals that are indicative of the degree to which said nanocrystals possess desired characteristics; and
(d) comparing values of said properties thus detected with said target range and adjusting the temperature of said heat transfer medium, the flow rate of said solution, or both, if needed to correct any deviation between said values of said detected properties and said target range.
22. A process in accordance with claim 21 in which said surface passivating reactants are a Zn-containing reactant and a reactant containing a member selected from the group consisting of S and Se, and said passivating coating is a coating of ZnY in which Y is a member selected from the group consisting of S, Se, and mixtures of S and Se.
23. A process in accordance with claim 21 in which step (c) is performed upon emergence of said product mixture from said reaction tube.
24. A process in accordance with claim 22 in which said surface passivating reactants are a dialkyl zinc and hexamethyldisilathiane.
25. A process in accordance with claim 21 further comprising cooling said product mixture between steps (b) and (c) to a temperature sufficiently low to quench said reaction.
26. A process in accordance with claim 21 in which said properties are optical features.
27. A process in accordance with claim 26 in which said optical features are photoluminescent emission spectra, and step (c) comprises irradiating said product mixture with light and detecting wavelength spectra of photoluminescent energy emitted from said nanocrystals.
28. A process in accordance with claim 26 in which said optical features are absorbance, and step (c) comprises irradiating said product mixture with light and detecting absorbance spectra of said nanocrystals.
29. A process in accordance with claim 26 in which said optical features are light scattering, and step (c) comprises irradiating said product mixture with light and detecting the presence of light scattering by said nanocrystals.
30. A process in accordance with claim 21 in which said heat transfer medium of step (b) is maintained at a temperature of from about 100° C. to about 400° C.
31. A process in accordance with claim 21 in which said coordinating solvent is a member selected from the group consisting of alkyl phosphines, alkyl phosphine oxides, pyridines, furans, ethers, amines, and alcohols.
32. A process in accordance with claim 21 in which said coordinating solvent is a member selected from the group consisting of tri-n-octylphosphine and tri-n-octylphosphine oxide.
33. A process in accordance with claim 21 in which said coordinating solvent is a mixture of tri-n-octylphosphine and tri-n-octylphosphine oxide.
34. A process in accordance with claim 21 in which step (d) comprises adjusting the temperature of said heat transfer medium.
35. A process in accordance with claim 21 in which step (d) comprises adjusting the flow rate of said solution.
36. Apparatus for the fabrication of monodisperse luminescent semiconductor nanocrystals having detectable properties within a target range, said apparatus comprising:
a thermally conductive reaction tube embedded in a heat transfer medium;
heating means for maintaining said heat transfer medium at a temperature sufficiently high to initiate a nanocrystal-forming reaction between nanocrystal-forming reactants passing therethrough;
pump means for continuously passing a fluid carrier bearing nanocrystal-forming reactants through said thermally conductive reaction tube at a reaction flow rate;
monitor means for monitoring a product stream borne by said fluid carrier to detect properties of any nanocrystals formed therein that are indicative of the degree to which said nanocrystals possess desired characteristics; and
control means for comparing values of said optical features thus detected with said target range and adjusting the temperature of said heat transfer medium, the pump rate of said pump means, or both, if needed to correct any deviation between said values of said detected optical features and said target range.
37. Apparatus in accordance with claim 36 in which said properties are optical features.
38. Apparatus in accordance with claim 37 in which said optical features are photoluminescent emission spectra, and said monitor means comprise means for irradiating said product mixture with light and detecting wavelength spectra of photoluminescent energy emitted from said nanocrystals.
39. Apparatus in accordance with claim 37 in which said optical features are absorbance, and said monitor means comprise means for irradiating said product mixture with light and detecting absorbance spectra of said nanocrystals.
40. Apparatus in accordance with claim 37 in which said optical features are light scattering, and said monitor means comprise means for irradiating said product mixture with light and detecting the presence of light scattering by said nanocrystals.
41. Apparatus in accordance with claim 36 further comprising cooling means for cooling said product mixture borne by said fluid carrier upstream of said monitor means.
42. Apparatus in accordance with claim 36 in which said monitor means monitors said product stream as it emerges from said thermally conductive reaction tube.
43. Apparatus in accordance with claim 36 in which said control means adjusts the temperature of said heat transfer medium.
44. Apparatus in accordance with claim 36 in which said control means adjusts the pump rate of said pump means.
Description
BACKGROUND OF THE INVENTION

[0001] 1. Field of the Invention

[0002] This invention resides in the field of nanocrystalline materials and processes for their manufacture.

[0003] 2. Description of the Prior Art

[0004] Quantum-sized particles, i.e., those having diameters within the range of about 0.1 nm to about 50 nm, also known as quantum dots or nanocrystals, are known for the unique properties that they possess as a result of both their small size and their high surface area. Some of these particles have unique magnetic properties that make the particles useful in electronic data systems such as recording media, in ferro fluids, and in magnetic tagging elements. Luminescent nanocrystals are particularly useful as detectable labels such as oligonucleotides tags, tissue imaging stains, protein expression probes, and the like, in applications such as the detection of biological compounds both in vitro and in vivo. Luminescent nanocrystals offer several advantages over conventional fluorophores, particularly for multiplexed and/or high sensitivity labeling. Nanocrystals typically have larger absorption cross sections than comparable organic dyes, higher quantum yields, better chemical and photochemical stability, narrower and more symmetric emission spectra, and a larger Stokes shift. Furthermore, the absorption and emission properties vary with the particle size and can be systematically tailored.

[0005] A variety of methods have been reported for the preparation of nanocrystals. These methods include inverse micelle preparations, arrested precipitation, aerosol processes, and sol-gel processes. A method commonly used for the preparation of binary nanocrystals is one in which an organometallic and elemental set of nanocrystal precursors is injected into a hot solvent as the solvent is being stirred. Product nucleation can begin immediately, but the injection causes a drop in the solvent temperature, which tends to halt the nucleation process. Nucleation and particle growth can be continued by heating the reaction mixture with further stirring, and the temperature can be dropped to stop the reaction when the desired particle size is obtained. As a result, the success of this batchwise “stirred-pot” method is strongly affected by system parameters such as the initial temperature of the solvent, the injection temperature and in particular the injection rate, the stirring efficiency, the concentrations of the reactant materials, the length of time that the mixture is held at the reaction temperature, and the efficiency of the cooling both after injection and after the desired endpoint is achieved. Some of these parameters are difficult to control with precision, and this can lead to poor reproducibility of the product. The lack of precise control also leads to nanocrystals with surfaces that are nonuniform, products that are readily degradable, and/or nanocrystals with low emission quantum yields.

[0006] The initial reaction conditions, i.e., the manner and conditions under which the reaction is initiated, are particularly important in controlling the quality and uniformity of the product, and far more so than in other types of syntheses. Stirred-pot methods suffer in this regard since there are limits to how rapidly and uniformly the temperature of the reaction mixture can be changed or otherwise controlled. The temperature drop that occurs upon injection of the precursors will vary with the precursor temperature prior to injection, the volume of precursor injected and its rate of injection, the volume of the heated solvent, and the stirring efficiency. The difficulty in cooling rapidly when terminating the reaction often means that a lower reaction temperature must be used as a means of avoiding excess reaction. Further difficulties with stirred-pot methods are that they often involve the injection of large volumes of flammable or pyrophoric materials at very high temperatures, or the rapid evolution of gases, all of which present safety hazards.

[0007] Control of the properties of nanocrystals by the application of coatings or shells has been reported, notably in International Patent Publication No. WO 99/26299 (PCT/US98/23984), “Highly Luminescent Color-Selective Materials,” Massachusetts Institute of Technology, applicant, international publication date May 27, 1999, and references cited therein. The application of an inorganic shell, for example, can increase the quantum yield of the nanocrystal as well its chemical stability and photostability. The techniques for applying a shell are stirred-pot techniques that are usually similar to those used for the preparation of the core. Like the diameter of the core, the thickness of the shell affects the properties of the finished product, and the thickness will vary with the same system parameters that affect the core. The difficulties in controlling these parameters in a stirred-pot system lead to difficulties in controlling the nature and quality of the final product.

SUMMARY OF THE INVENTION

[0008] The limitations and difficulties described above and others encountered in the preparation of nanocrystals are addressed by the present invention, which resides in processes and apparatus for the production of monodisperse luminescent semiconductor nanocrystals, for the application of a coating to nanocrystal cores, and for both. The manufacture of nanocrystals in accordance with this invention is accomplished by first dissolving or dispersing precursor materials capable of reacting to form nanocrystals in a solvent, for example a coordinating solvent, and introducing the resulting reaction mixture into a reaction tube that is embedded or immersed in a heat transfer medium. Likewise, the application of a coating to nanocrystal cores in accordance with this invention is accomplished by dispersing the nanocrystal cores in a solvent, for example a coordinating solvent, in which are dissolved the precursor materials for the coating, and introducing this reaction mixture into the reaction tube. In either case, the heat transfer medium is maintained at the desired reaction temperature, and the reaction mixture is passed continuously through the tube. The internal diameter of the tube is preferably small enough to promote rapid transfer of heat from the tube walls to the center of the fluid stream flowing through the tube and hence rapid heating of the continuously flowing stream to the reaction temperature. In addition to the tube diameter, the flow rate is varied and adjusted, and the tube length selected, to permit control of the reaction. Flow rate, temperature and pressure are all controllable, and in preferred embodiments the reaction is quenched by cooling the product stream upon its emergence from the reaction tube by any of various conventional cooling techniques.

[0009] Characteristic properties of the product stream, such as optical properties, electrical properties, magnetic properties, electromagnetic properties, and the like are detected and a comparison is made between the detected values and a predetermined or preselected target range that is indicative of the product quality sought to be achieved. Any discrepancy or deviation between the detected values and target range can then be used to adjust the variable reaction conditions, such as the temperature of the heat transfer medium, the flow rate of the reaction mixture through the tube, or both, until the product changes sufficiently that the detected values fall within or otherwise conform to the target range.

[0010] Reaction apparatus in accordance with this invention includes a thermally conductive reaction tube of sufficiently small internal diameter to accomplish effective heat transfer in the flowing stream, a heat transfer medium in thermal contact with the exterior of the reaction tube, a pump or other fluid-driving component for continuously supplying a reactant or precursor mixture to the reaction tube, a monitoring unit to evaluate, measure, or otherwise detect the properties of the product stream, preferably but not necessarily as the product stream leaves the reaction tube, as an indication of the nature and quality of the nanocrystals formed in the reaction mixture during its passage through the reaction tube, and optionally a control loop to adjust the reaction conditions in the tube to correct for any discrepances between the detected values and the target range.

[0011] Further details of these features and the various preferred embodiments of the several aspects of this invention are described below.

BRIEF DESCRIPTION OF THE DRAWINGS

[0012]FIG. 1 is a process flow diagram of one embodiment of the present invention.

[0013]FIG. 2 is a process flow diagram of a second embodiment of the present invention.

[0014]FIG. 3 is a superimposed plot of emission spectra of nanocrystals formed by the process and apparatus of the present invention under various reaction conditions.

DETAILED DESCRIPTION OF THE INVENTION AND SPECIFIC EMBODIMENTS

[0015] The terms “semiconductor nanocrystal,” “quantum dot,” “Qdot™ nanocrystal,” or simply “nanocrystal” are used interchangeably herein and refer to an inorganic crystallite between about 1 nm and about 1000 nm in diameter or any integer or fraction therebetween, more typically about 2 nm to about 20 nm (such as 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 nm). A semiconductor nanocrystal is capable of emitting electromagnetic radiation upon excitation (i.e., the semiconductor nanocrystal is luminescent) and includes a “core” of one or more first semiconductor materials, and may be surrounded by a “shell” of a second semiconductor material. A semiconductor nanocrystal core surrounded by a semiconductor shell is referred to as a “core/shell” semiconductor nanocrystal. The surrounding “shell” material typically has a bandgap energy that is larger than the bandgap energy of the core material and can be chosen to have an atomic spacing close to that of the “core” substrate. The core and/or shell can be a semiconductor material including, but not limited to, those of the Groups II-VI (ZnS, ZnSe, ZnTe, CdS, CdSe, CdTe, HgS, HgSe, HgTe, MgS, MgSe, MgTe, CaS, CaSe, CaTe, SrS, SrSe, SrTe, BaS, BaSe, BaTe, and the like) and III-V (GaN, GaP, GaAs, GaSb, InN, InP, InAs, InSb, and the like) and IV (Ge, Si, and the like), and alloys or mixtures thereof.

[0016] By “luminescence” is meant the process of emitting electromagnetic radiation (light) from an object. Luminescence results from a system that is “relaxing” from an excited state to a lower state with a corresponding release of energy in the form of a photon. These states can be electronic, vibronic, rotational, or any combination of these three. The transition responsible for luminescence can be stimulated through the release of energy stored in the system chemically or added to the system from an external source. The external source of energy can be of a variety of types including chemical, thermal, electrical, magnetic, electromagnetic, physical, or any other type excited by absorbing a photon of light, by being placed in an electric field, or through a chemical oxidation-reduction reaction. The energy of the photons emitted during luminescence can be in a range of low-energy microwave radiation to high-energy x-ray radiation. Typically, luminescence refers to photons in the range from UV to IR radiation.

[0017] “Monodisperse particles” include a population of particles wherein at least about 60% of the particles in the population, more preferably 75% to 90% of the particles in the population, or any integer within this range, fall within a specified particle size range. A population of monodisperse particles deviates less than 10% rms (root-mean-square) in diameter and typically less than 5% rms. In addition, upon exposure to a primary light source, a monodisperse population of semiconductor nanocrystals is capable of emitting energy in narrow spectral linewidths, as narrow as 12 nm to 60 nm full width of emissions at half peak height (FWHM), and with a symmetric, nearly Gaussian line shape. As one of ordinary skill in the art with recognize, the linewidths are dependent on, among other things, the size heterogeneity, i.e., monodispersity, of the semiconductor nanocrystals in each preparation. Certain single semiconductor nanocrystal complexes have been observed to have FWHM as narrow as 12 nm to 15 nm.

[0018] One of the implementations of this invention is the formation of nanocrystalline particles (or nanocrystal cores for encapsulation). This is done in a continuous-flow manner, and precursors known in the art may be used. Useful precursors are many and varied, depending on the type of nanocrystals to be prepared and the intended use of the nanocrystals. One of the various classes of nanocrystals are those that emit light, and examples are those bearing the empirical formulae CdX or ZnX in which X is a chalcogen. Preferred chalcogens are S, Se and Te, with Se particularly preferred. Preferred nanocrystals are CdSe, CdS, CdTe, and ZnSe. Reactants capable of forming nanocrystals of these materials are organocadmium and organozinc compounds as the source of the Cd and Zn, respectively, and elemental chalcogen or chalcogen-containing compounds as the source of the chalcogen.

[0019] Other implementations of the invention are the coating of pre-formed nanocrystal cores. The coating is likewise performed in a continuous-flow manner, by placing the cores in a suspension in which starting material(s) that form the coating are dissolved. Coatings of various compositions known in the art can be applied in this manner. One class of coatings are those serving to passivate the cores to improve optical properties such as quantum yield. Among this class are those bearing the empirical formula ZnY in which Y is S, Se, or a mixture thereof.

[0020] Whether the reaction is a nanocrystal core-forming reaction or a coating reaction, the process is often facilitated by performing the reaction in the presence of a coordinating solvent or by addition of a coordinating additive. The terms “coordinating solvent” and “coordinating additive” as used herein denote a solvent or other chemical additive that enters into molecular coordination with the atoms in the reactants that combine to form the nanocrystalline materials or the reactants that combine to form the coatings on the nanocrystal core surfaces or with the nanocrystals themselves. The coordinating solvent thus enhances the solubility of the reactants while also serving as a means of modulating the reactivity of the precursors or the growing nanoparticles. A wide range of solvents that function in this manner can be used, and a preferred group are alkyl phosphines, alkyl phosphine oxides, pyridines, furans, ethers, amines and alcohols. Coordinating solvents that are particularly preferred for cadmium chalcogenide nanocrystals are tri-n-octylphosphine and tri-n-octylphosphine oxide. A coordinating solvent that is particularly preferred for zinc chalcogenide nanocrystals is hexadecylamine. In certain embodiments of the invention, notably Cd-Se systems, a mixture of tri-n-octylphosphine and tri-n-octylphosphine oxide offers particular benefits, the former potentially serving as a preferential coordinator for Se and the latter for Cd.

[0021] The reactions performed in accordance with this invention are performed on a continuous-flow basis in the thermally conductive reaction tube. The tube is thermally conductive in order to permit efficient heat transfer between the heat transfer medium surrounding the tube and the reaction mixture flowing through the tube. As will be well appreciated by those skilled in the art, the efficiency of the heat transfer is also dependent on the internal diameter and wall thickness of the tube and the composition of the heat transfer medium surrounding the tube. While this invention is not intended to be limited to specific values for the diameter and length of the tube, the optimal values of these dimensions will be determined by considerations of the viscosity of the reaction mixture and the pressure drop needed to drive the reaction mixture through the tube, both of which will depend on the concentration of the reactants in the reaction mixture as well as the temperature. These types of determinations can be made by routine experimentation, or by the use of relationships that are well known among those skilled in fluid dynamics. In general, however, successful results will be obtained with a reaction tube having an internal diameter of about 1.0 mm or less, and preferably within the range of about 0.1 mm to about 1.0 mm, and most preferably within the range of from about 0.25 mm to about 0.8 mm. The reaction tube will have a wall thickness be great enough to provide dimensional stability and sturdiness to the tube but the wall will otherwise be as thin as possible. If the tube material itself has a high heat conductivity, then the tube will contribute to the heat transfer and the choice of wall thickness will be of little importance. In some cases, as described below, the reaction tube may be continuous with the surrounding heat transfer medium, with essentially no wall thickness.

[0022] The temperature changes imposed on the reaction mixture during its passage through the reaction tube will likewise depend on the tube diameter, as well as the flow rate of the reaction mixture. Flow rates may vary, and the invention is not intended to be limited to specific flow rates. Nevertheless, effective results will be achieved at flow rates within the range of from about 10 μL per minute to about 1000 μL per minute, preferably from about 30 μL per minute to about 300 μL per minute.

[0023] The degree or extent of reaction also depends on the concentrations of the reactants, the length of the reaction tube, and the temperature and pressure at which the reaction tube is maintained. None of these operating parameters are limited to specific values in this invention, and each may vary considerably in accordance with the type of product being prepared and the characteristics and qualities that are sought in the product. The appropriate selection of these parameters is a matter of routine skill to those experienced or familiar with batchwise processes for these reactions. In most applications, it is contemplated that the reaction tube will be from about 3 cm to about 300 cm in length, preferably from about 10 cm to about 100 cm in length. Likewise, the most typical temperatures will be at least about 100° C., and preferably within the range of from about 100° C. to about 400° C., more preferably within the range of about 250° C. to about 400° C. These temperature ranges are applicable to both the nanocrystal core-forming reaction and the coating reaction.

[0024] The reaction tube itself may be of any configuration that will permit continuous flow and that can be immersed, embedded or otherwise placed in full thermal contact with a heat transfer medium. The tube can be straight, serpentine, coiled, or otherwise shaped. The tube can be made of a variety of materials based upon requirements such as thermal conductivity, flexibility, or chemical reactivity. The tube can also be of composite construction, such as glass-coated stainless steel, to obtain particular combinations of properties. The heat transfer medium can be gas, liquid, or solid. With gas or liquid media, circulation can improve the heat transfer efficiency by creating a more uniform temperature. A solid heat transfer medium can be formed by casting or molding a heat conductive material around the reaction tube. If desired, the reaction tube can be formed by forming a bore through a solid block of heat transfer medium, the bore itself serving as the tube. A particularly effective arrangement is the use of a reaction tube with a block of heat conductive metal cast around the tube. Materials of construction are selected as those that are chemically inert to the reaction materials while providing effective heat transfer.

[0025] Monitoring of the product stream is performed by conventional apparatus for the on-line detection of the determinative or characteristic properties of the product stream. Examples of these properties are absorbance of electromagnetic radiation, emission of electromagnetic radiation, both absorbance and emission of electromagnetic radiation, static or dynamic light scattering, refractive index, conductance, and magnetic susceptibility. Static light scattering, dynamic light scattering, or refractive index, for example, can be used to assess the size distribution of the particles. Conductance can be used with charged particles to obtain a particle count, and magnetic susceptibility can be used with magnetic or paramagnetic particles to determine the size distribution, particle count, or both. All of these properties can be detected by techniques that are known in the art using instrumentation that is commercially available. In the preferred practice of the invention, the properties detected are optical properties such as, for example, emission intensity, emission wavelength, full width at half maximum peak height, absorption, light scattering, fluorescence lifetime, or combinations of these properties. Detection can be performed at a site downstream of the reaction tube and heat transfer medium. Alternatively, detection can be performed on-line within the reaction tube itself, in which case a tube that permits such detection is used. For detection of optical properties, for example, suitable tubes are those that are optically transparent. In preferred implementations of this invention, the product mixture is cooled at or near the site where detection is performed. Thus, when on-line detection is performed, the product mixture is preferably cooled as it emerges from the heat transfer medium but before it reaches the on-line detection point. Cooling in these embodiments is done to lower the temperature of the product stream enough to substantially quench any reaction still occurring in the moving stream and to standardize the detection temperature, thereby eliminating variations in the optical properties due to temperature. Cooling can be accomplished by passing the product stream through a cooling tube embedded or immersed in a cooling medium in a manner analogous to the heat transfer medium used to heat the starting materials to reaction temperature. It is often sufficient to cool the material passively by simply removing the heating element at the end of the reaction zone. Alternatively, cooling can be achieved by diluting the product stream with additional solvent at an appropriately low temperature. In certain embodiments the injection of additional solvent provides an additional benefit—i.e., when the solvent in which the reaction takes place is a mixture of species such as tri-n-octylphosphine and tri-n-octylphosphine oxide, one of which has a melting point above room temperature, the addition of a further amount of a lower-melting solvent species for cooling purposes can prevent freezing of the higher-melting species and facilitate handling of the product stream.

[0026] The properties that are monitored may be any detectable properties that serve as an indication of the size of the nanocrystals, the thickness of the coating, the surface characteristics, or in general the degree or quality of reaction having occurred in the reaction tube. Absorbance is readily measured by irradiating the product stream with light and determining the absorption spectra. Light scattering is readily measured by illuminating the product stream and detecting the direction or amount of scattered light, either one being characteristic of the properties of the nanocrystals and their chemical composition. Photoluminescence is readily measured by irradiating the product stream with light of an appropriate wavelength to excite the nanoparticles and detecting the emission spectra resulting from the excitation. Conventional spectrophotometers or other light detecting devices can be used.

[0027] Comparison of the spectra with a target range is then performed to determine whether adjustments are needed to the reaction conditions to shift the spectra into the target range. If the shift can be achieved by a change in the reaction temperature, the comparison can serve as a means of determining how much and in which direction to modify the temperature of the heat transfer medium and hence the temperature in the reaction tube. The comparison can be performed visually in a trial run or at the start of the process or at any time during the progress of the reaction, and adjustments to the temperature can be made manually by the operator. Alternatively, the comparison can be performed by automated instrumentation, and if desired, on a continuous basis, with a corresponding adjustment in temperature or flow rate until the comparison produces a favorable result.

[0028] The Figures attached hereto illustrate various embodiments of the invention in the form of process flow diagrams.

[0029]FIG. 1 is a process flow diagram illustrating one example of a rudimentary system embodying the principles of this invention. The first stage is a reagent preparation stage 11 in which nanocrystal precursors (for those embodiments involving the formation of nanocrystal cores) are dissolved in a coordinating solvent, or in which preformed nanocrystal cores (for those embodiments involving the coating of the preformed cores) are suspended in a solution of coating precursors dissolved in a coordinating solvent. In either case, the resulting reaction mixture is transferred by a computer-controlled syringe pump 12 to the heated reactor 13, which consists of a stainless steel tube 14 whose inner diameter is 0.01 inch to 0.03 inch (0.25 mm to 0.76 mm) around which a zinc block 15 has been cast. The zinc block is provided with temperature detection and heating connections that permit temperature control of the block 15 (and hence the tube 14) to various temperatures up to about 400° C. At the outlet of the heated reactor 13, the product stream passes through a flow-through monitoring cell 16 which includes an ultraviolet light source to excite the nanocrystals in the product stream and a CCD-based miniature spectrometer to measure the emission spectra from the nanocrystals. The emission spectra can be monitored visually by the operator and adjustments made to the temperature of the heated reactor 13, the syringe pump 12, or both, to achieve nanocrystals that emit the desired spectra. Alternatively, the emission spectra detected by the monitor can be transmitted to an automated controller 17 which will process the data, compare it to a target spectrum, and transmit signals to either the heated reactor, the syringe pump, or both, to correct the temperature and/or flow conditions. This can be done on a continuous basis until the detected spectra conform to the target spectra to a degree that is acceptable to the operator. The finished nanocrystals are collected in a product recovery unit 18 when the parameters have been adjusted sufficiently to achieve the desired spectral output.

[0030] An optional added feature in FIG. 1 is the provision of the introduction of cooled diluent 19 to the product stream emerging from the reactor 13 for purposes of quenching the reaction prior to the product mixture reaching the monitoring cell. The diluent 19 is fed through a metering pump 20 to an on-line mixing chamber 21 where it mixes with the product stream.

[0031] In variations of the system illustrated in FIG. 1, two or more reagents can be supplied by individual pumping units, each under separate control from a centralized controller. As in FIG. 1, the controller signals to the pumping units can be modulated by comparisons of the spectral output of the product stream, thereby adjusting the relative feed rates of the reagents to achieve a product having the desired spectral characteristics. Likewise, monitoring cells can be placed at two or more locations along the process flow path to monitor the progress of the reaction. This will allow different reagents to be added at different stages of the process, and is particularly useful when the process is used both to form the nanocrystal core and to coat the core. The outputs of all monitoring cells will be received and processed either by individual controllers or by a common controller, and resulting signals emitted by the controller(s) can be used to drive adjustments in the temperatures or pump rates at various points along the process path. For reactions performed in two or more stages, separately controlled heating units can be used so that each stage can be individually controlled to its own optimum temperature. For systems that include monitoring cells at two or more locations, individual cooling sites can be incorporated immediately upstream of the entry to each cell. In certain systems, it may also be desirable to extract, concentrate, or isolate product from the product stream at points between successive stages of the process. Operations such as these can be performed by centrifugation, precipitation, filtration, and other similar treatments that are well known to those with experience in process chemistry.

[0032]FIG. 2 is a process flow diagram for a process that includes first preparing the nanocrystal core and then applying a coating to the core, incorporating several of the additional features of the preceding paragraph. The core is formed in a heated reactor 41 which is similar in construction to that of FIG. 1, supplied by two reagents 42, 43, each fed by individual metering pumps 44, 45, then preheated 46, 47, and combined in a mixing chamber 48 prior to entry into the reactor 41. The preheating is optional and may be used when the resulting mixture might suffer a drop in temperature due to the addition of one of the components, or when one of the solvents is a solid at room temperature. The two metering pumps 44, 45 drive the reaction mixture through the reactor 41, and the emerging dispersion of nanocrystal cores is cooled by the introduction of a cooled diluent 49, likewise supplied through a metering pump 50 and mixed with the core dispersion in a mixing chamber 51. The cooled product stream passes through a monitoring cell 52 which detects the optical properties of the nanocrystal cores in the product stream and forwards the data to a controller 53 where the data is compared to a target and corrective output signals are transmitted to the two reagent metering pumps 44, 45, and to the heating unit on the heated reactor 41.

[0033] The core suspension, upon emerging from the monitor 52, is combined with coating agent(s) to prepare for the coating reaction which, like the nanocrystal-forming reaction, occurs at an elevated temperature. The coating agent(s) 54 are supplied through a metering pump 55 and mixed with the core dispersion in a mixing chamber 56. The flow diagram presents two options for delivering the core suspension to the mixing chamber—direct delivery and delivery through a processing unit 57 where the core suspension is concentrated or otherwise treated as described above to prepare the cores for coating. In either case, the new reaction mixture enters the second heated reactor 61, which is similar in construction and principle to the first heated reactor 41. The product stream emerging from the second heated reactor contains the coated nanocrystals, and is cooled by a diluent 62 fed through a metering pump 63 and mixed with the product stream in a mixing chamber 64. The cooled coated nanocrystal stream then enters a second monitoring cell 65 which detects the optical properties of the coated cores and forwards the data to a second controller 66 where the data is compared to a target and corrective output signals are transmitted to the coating agent metering pump 53 and the heating unit on the heated reactor 61. The product stream is then processed in a processing unit 67 where the coated nanocrystals are recovered from the solvent and any unreacted material.

[0034] The following example is offered as illustration, and is not intended to impose limits on the scope of the invention.

EXAMPLE

[0035] This example demonstrates the use of the present invention in preparing nanocrystals of CdSe, and the ability of an on-line fluorescence monitoring cell to differentiate between products prepared at different reaction temperatures, flow rates and the like.

[0036] A solution was prepared by dissolving 0.179 g of selenium in 16 mL of tri-n-octylphosphine (TOP) and adding 0.115 mL of dimethyl cadmium. Separately, tri-n-octylphosphine oxide (TOPO) (12.5 g) was heated under vacuum to 180° C. and then maintained at 65° C. under dry nitrogen. The heated TOPO was then combined with 7 mL of the TOP solution of selenium and dimethyl cadmium. A continuous-flow reaction was then performed, using the apparatus depicted in FIG. 1, with a reaction tube consisting of 50 cm of 0.03-inch (0.76 mm) stainless steel tubing coiled tightly and cast into a zinc block. The flow rate of the reaction mixture through the tubing was 200 μL/minute, and the zinc block was variously maintained at temperatures of 280° C., 290° C., 300° C., 310° C., 320° C., 330° C., 340° C., 350° C., and 365° C.

[0037] Luminescence spectra were obtained for the emerging product formed at each of the nine reaction temperatures, and the results are shown in superimposed curves in FIG. 3. The superimposed curves show that each reaction temperature produced a distinct curve, and that adjustment of the reaction temperature can therefore be used to obtain a product of a particular emission spectrum while still maintaining a narrow size distribution of the particles, as indicated by the peak widths.

[0038] The foregoing description is offered for illustrative purposes. Those skilled in the art will recognize that further modifications, variations and substitutions in the process and apparatus parameters, such as temperatures, flow rates, reactant materials and other components of the reaction and product mixtures, as well as the number and arrangement of operating units in the process flow path, can be made without departing from the spirit and scope of the invention.

Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US7511016 *Jul 7, 2004Mar 31, 2009Mosamedix B.V.Annexins, derivatives thereof, and annexin-cys variants, as well as therapeutic and diagnostic uses thereof
US8017235Aug 17, 2004Sep 13, 2011National Institute Of Advanced Industrial Science And TechnologyMethod for manufacturing fine composite particles, apparatus for manufacturing fine composite particles, and fine composite particles
EP2218762A2Jul 17, 2002Aug 18, 2010Life Technologies CorporationLuminescent nanoparticles and methods for their preparation
EP2599898A1 *Dec 1, 2011Jun 5, 2013Bayer Intellectual Property GmbHContinuous synthesis of high quantum yield InP/ZnS nanocrystals
WO2011008151A1 *Jul 9, 2010Jan 20, 2011Olsson RichardReal time monitored synthesis of ultra low coercivity magnetic nanoparticles with narrow size distribution
WO2013079423A1 *Nov 26, 2012Jun 6, 2013Bayer Intellectual Property GmbhContinuous synthesis of high quantum yield inp/zns nanocrystals
Classifications
U.S. Classification117/69
International ClassificationC30B7/00
Cooperative ClassificationB82Y10/00, B82Y30/00, C30B7/00
European ClassificationB82Y10/00, B82Y30/00, C30B7/00
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