MXPA02003284A

MXPA02003284A - Method of manufacture of colloidal rod particles as nanobar codes.

Info

Publication number: MXPA02003284A
Application number: MXPA02003284A
Authority: MX
Inventors: J Dietz Louis
Original assignee: Surromed Inc
Priority date: 1999-10-01
Filing date: 2000-10-02
Publication date: 2002-10-04
Also published as: EP1238125A1; JP2003511556A; EP1238125A4; WO2001025510A1; CA2387992A1; AU1495101A

Abstract

An apparatus and synthetic methods for manufacture of segmented nanoparticles are described. The nanoparticles of the present invention may be comprised of any material, including metal, metal chalcogenide, a metal oxide, a metal sulfide, a metal selenide, a metal telluride, a metal alloy, a metal nitride, a metal phosphide, a metal antimonide, a semiconductor, a semi metal or any organic or inorganic material. The method employs electrochemical deposition of metals inside a template wherein the process is improved, separately and collectively, by i) electroplating in an ultrasonication bath; and ii) controlling the temperature of the deposition environment, preferably by using a recirculating temperature bath.

Description

METHOD PE MANUFACTURE OF CYLINDER COLOMBIAN PARTICLES AS NANOBARRAS CODES FIELD OF THE INVENTION The present invention is directed to methods of manufacturing nanoparticles and methods for such manufacturing. In certain preferred embodiments of the invention, nanoparticles can be used to encode information and therefore serve as labels, labels and molecular (or cellular) substrates.

BACKGROUND OF THE INVENTION The present invention relates to methods of manufacturing segmented particles and assemblies of differentiable particles (which may or may not be segmented). Undoubtedly, there has been a paradigm shift in what is traditionally defined as bioanalytic chemistry. A main focus of these new technologies is to generate what could be called "information content increase by volume". This term covers several methods, from the reduction of the volume of sample required to carry out an assay, to highly parallel measurements ("nultiplexing"), such as those involving immobilized molecular arrays, until the incorporation of second (or third) channels of information, such as in 2-D gel electrophoresis or electro-vacuum EC MS / MS.

Unfortunately, many of these seemingly revolutionary technologies are limited due to their dependence on relatively pedestrian materials, methods and analysis. For example, the development of DNA microarray ("gene fragments") for the analysis of gene expression and genotyping by Affymetrix, Incyte and similar companies has generated the means to immobilize up to 20,000 different fragments or full length pieces of DNA in a spatially defined arrangement of 1 cm2. At the same time, however, the use of these fragments requires the hybridization of the DNA in solution to DNA immobilized on a flat surface, which is marked both by a decrease in the efficiency of the hybridization (especially for the cDNA) and an even greater degree of non-specific binding. It is not clear if those problems can be completely overcome. In addition, there is a general sense of disillusionment both about the cost of acquiring external technology and the execution time required to develop a DNA array internally. A second example of how to open the way may be delayed by the inferior tools in pharmaceutical discovery by combined chemistry. So far, latex beads with a diameter of 5 to 10 μm, in phase in solution, are used extensively as sites for molecular immobilization. Exploiting the widely adopted "divide and join" strategy, libraries of up to 100,000 compounds can be generated simply and quickly. As a result, the bottleneck in drug discovery has deviated from synthesis to separation, and it is equally important, the identification of compounds (ie, which compound is found in which bead?). Current methods up to now comprise "bead coding", whereby each synthetic step applied to a bead is recorded by the parallel addition of an organic "code" molecule; reading the code allows the identity of the drug found on the pearl to be identified. Unfortunately, the "code reading" protocols are far from optimal: in each strategy, the code molecule must. > < _. cleaved and separated from the pearl and analyzed separately CLAP, mass spectrometry or other methods. In other words, currently there is no way to identify potentially interesting candidate drugs by direct, rapid interrogation of the beads on which they reside, although there are numerous methods of separation or selection in which such capacity would be desirable. Two alternative technologies with potential relevance for both combined chemistry and genetic analysis involve "self-encoded beads", in which a spectrally identifiable bead substitutes a spatially defined position. In the method whose pioneers are Walt and his collaborators, the beads are chemically modified with a ratio of fluorescent dyes that are intended to uniquely identify the beads, which are then further modified with a unique chemistry (for example an antibody or enzyme). different). The beads are then randomly dispersed over a recorded fiber arrangement so that a pearl is associated with each fiber. The identity of the bead is determined by its fluorescent reading, and the analysis is detected by fluorescence reading on the same fiber in a different spectral region. The seminal paper (Michael et <; *? /., Anal.Chem.ZQ, 1242-1248 (1998)) on this topic indicates that with 6 different tints (15 combinations of pairs) and comparison 10 different relationships of dyes, 150"unique optical signatures" could be generated , each one representing a different pearl "flavor". A very similar strategy is described by Luminex workers, who combine pearls s? 3? Oriz < Lists ready for chemical modification (100 commercially available) with an analysis similar to flow cytometry (see, for example, McDade et al., Med.Rev.Diag.Indust 12.75-82 (1997)). Once, that the flavor of the particle is determined by fluorescence, and once the biochemistry is placed on the bead, any spectrally distinct fluorescence generated due to the presence of the analyte can be read. Note that since it is currently configured it is necessary to use a laser color to interrogate the flavor of the particle, and another, separate laser to excite the bioassay fluorophores. A more significant aspect with the self-encoded latex beads are the limitations imposed by the broad bandwidth associated with molecular fluorescence. If the frequency spaces of those used both for coding and for bioassay analysis, it is difficult to imagine how, for example, up to 20,000 different flavors could be generated. This problem can be alleviated somewhat by the use of glass-coated quantum dot combinations, which exhibit narrower fluorescence bandwidth. (See, for example, Bruchez et al., Science, 281, 2013-2016 (1998)). However, these "designer" nanoparticles are very difficult to prepare, and so far there are more types of fluorophores than quantum dots (published). If, however, it were possible to generate very large numbers of particles intrinsically differentiable by some means, particle-based bioanalysis would be exceptionally attractive, since it could be considered as a unique technological platform for high-information research areas; including combined chemistry, genomics and proteomics (via multiplexed immunoassays). Previous work has originally taught how metal can be deposited in the pores of a metallized membrane to produce an array of metallic nanoparticles embedded in the host. His focus was on the optical and / or electromagnetic properties of those materials. A similar technique was used to produce segmented cylindrical magnetic nanoparticles in a host membrane, where the composition of the particles was varied throughout. In no case, however, have been prepared particles in the form of bar, freestanding, with variable compositions throughout its length. * In fact, metal nanoparticles have never been reported in the form of cylinders or "freestanding" bars of a single composition, in which the length is at least one micron. Similarly, metal-shaped rod-shaped metal nanoparticles not included or otherwise contained within such host materials have never been reported. See, Martín et al., Adv. Materials 11: 1021-25.

SUMMARY OF THE INVENTION Bar-shaped nanoparticles have been prepared whose composition varies along the length of the bar. These particles are referred to as nanoparticles or nanobar codes, although in reality some or all of the '.ÚS dimensions can c-stai in the micron size range. The present invention is directed to methods of manufacturing such nanoparticles. The present invention includes methods of manufacturing freestanding particles comprising a plurality of segments, wherein the length of the particle is from 10 nm to 50 μm and the width of the particle is from 5 nm to 50 μm. The segments of the particles of the present invention can be comprised of any material. Included among the possible materials are a metal, any metal chalcogenide, a metal oxide, a metal sulphide, a metal selenide, a metal tellurium, a metal alloy, a metal nitride, metal phosphite, an antimonide of metal, a semiconductor, a semimetal, any compound or organic material, any compound or inorganic material, a particulate layer of material or a composite material. The segments of the particles of the present invention can be comprised of polymeric materials, crystalline or non-crystalline materials, amorphous materials or glasses. In certain preferred embodiments of the invention, the particles are "functionalized" (i.e., they have their surface coated with an IgG antibody). Commonly, such functionalization can be linked on the selected segments or all, on the body or one or both points of the particle. Functionalization can actually coat segments over the entire particle. Such functionalization may include organic compounds, such as an antibody, an antibody fragment, or an oligonucleotide, inorganic compounds, and combinations thereof. Such functionalization may also be a detectable label or mark or comprise a species that will bind to a detectable label or tag. Also included within the present is an assembly or collection of particles comprising a plurality of particle types, wherein each particle is from 20 nm to 50 μm in length and is comprised of a plurality of segments, and where the types of particles are differentiable In the preferred embodiments, the particle types are differentiable based on differences in the length, width or shape of the particles and / or the number, composition, length or pattern of the segments. In other words, the particles are differentiable based on the nature of their functionalization or physical properties (for example, as measured by mass spectrometry or light diffraction). The present invention includes the manufacture of nanobar codes by electrochemical metal deposition within a template, _ > - "^ - - where the process is improved, separately and collectively, by i) electrodeposition in an ultrasonic bath, and ii) control of the temperature of the depositional environment, preferably by using a temperature bath with recirculation. included within the scope of the invention are methods for the parallel simultaneous manufacture of a plurality of different types of nanobar codes In accordance with one such method, a plurality of templates are maintained in a common SC 'ÜUÜH chamber and Electrochemical deposition is effected by controlling the deposition in each membrane by applying current selectively to predetermined electrodes associated with each of said membranes Also included within this invention is an apparatus for manufacturing nanobar codes comprising: a solution cell electrodeposition, a defined pore size template, means to apply current tea to produce the electrochemical deposition of a metal in the template, means for stirring the electrodeposition solution, such as an ultrasonic transducer, and temperature control means. Also included within this invention is an apparatus for the simultaneous manufacture of a plurality of different types of nanobar codes. In one embodiment, such an apparatus comprises: a solution chamber, a plurality of templates, means for selectively applying a current to each of the templates and control means for operating the apparatus.

BRIEF DESCRIPTION OF THE FIGURES Figure 1 is a perspective view of an apparatus for manufacturing a plurality of different types of nanobar codes. Figure 2 is a cross-sectional elevation view of the apparatus of the Figure 1.

DETAILED WRITTEN DESCRIPTION OF THE INVENTION The present invention is directed to methods of manufacturing nanoparticles. Such nanoparticles and their uses are described in detail in the US Application Serial No. 09 / 598,395, filed June 20, 2000, entitled "Colloidal Particles in the Form of Cylinders as Nanobar Codes ", incorporated herein in its entirety as a reference.

Presented concurrently with the present application, and also incorporated herein fully as a reference, are two US utility applications entitled "Methods of Particle Image Formation in Form of Colloidal Cylinders as Nanobars "and" Colloidal Particles in Form of Cylinders as Nanobar Codes. "The present application was presented as a continuation in part of application 09 / 598,395. The synthesis and characterization of multiple segmented particles is described in Martin et al., Adv. Materials 11: 1021-25 (1999). The article is hereby incorporated by reference in its entirety Also incorporated herein by reference in its entirety is US Provisional Patent Application Serial No. 60 / 157,326, filed on October 1, 1999, entitled "Autocoded Colloidal Metal Nanoparticles. by Bars ", Provisional US Patent Application Serial No. 60 / 189,151, filed on March 14, 2000, entitled" Nanoscale Bar Codes; "Provisional US Patent Application Serial No. 60 / 190,247, filed at March 17, 2000, entitled "Colloidal Cylindrical Particles as Bar Codes" and Provisional US Patent Application Serial No. 60 / 194,616, filed in Apri l 5, 2000, entitled "Nanobar Codes: Technological Platform for Phenotyping". Because bar coding is very widely used in the macroscopic world, the concept has been transferred to the molecular world in a variety of figurative manifestations. Thus, there are "bar codes" based on the analysis of open reading frame, barcode based on isotopic mass variations, barcodes based on chemical or physical report pearl chains, barcodes based on electrophoretic patterns of mRNA cleaved by restriction enzymes, bar-coded surfaces for repeatable imaging of biological molecules using scanning probe microscopes, and chromosomal (aka chromosomal painted) bar codes produced by in situ hybridization by fluorescence with multiple chromophores. All of those methods comprise ways to encode biological information, but none offers the range of advantages of the donor codes of the present invention, transformed to the nanoscale. The particles to be manufactured according to the present invention are referred to as nanoparticles, nanobar codes, bars and particles in the form of bars. To the extent that any of these descriptions can be considered as limiting the scope of the invention, the applied mark should be ignored. For example, although in certain embodiments of the invention, the composition of the particle contains information content, this is not true for all embodiments of the invention. Likewise, although nano-sized particles fall within the scope of the invention, not all particles of the invention fall within such a size range. In the preferred embodiments of the present invention, the nanobar code particles are produced by electromechanical deposition on an aluminum or polycarbonate template, followed by dissolution of the template, and are typically prepared by altering the electrochemical reduction of the metal ions, although they can be easily prepared by other means, with or without a template material. Typically, nanobar codes have widths between 30 nm and 1,000 nanometers, although they may have widths of several microns. Likewise, although the lengths (ie, the longitudinal dimension) of the materials are typically in the order of 1 to 15 microns, they can be easily prepared in lengths as long as 50 microns, and in lengths as short as 20 nanometers . In some embodiments, the nanobar codes comprise two or more different materials alternating throughout, although in principle as many as dozens of different materials could be used. Likewise, the segments could consist of non-metallic material, including, but not limited to polymers, oxides, sulfides, semiconductors, insulators, plastics, and even thin films (i.e., monolayers) of organic or inorganic species. When the particles of the present invention are produced by electromechanical deposition, the length of the segments (as well as their density and porosity) can be adjusted by controlling the amount of current (or electrochemical potential) passed in each electrodeposition step; as a result, the cylinder or bars resembles a "bar code" on a nanometric scale, with each segment length (and identity) programmable in advance. Other forms of deposition can achieve the same result. For example, it can be achieved via a non-electrolytic process and in an electrochemical deposition by controlling the electrode area, the constant heterogeneous ratio, the concentration of the electrolytic coating material and the potential and combination thereof (collectively referred to herein as electrochemical deposition) . The same results could be achieved using another manufacturing method in which the length or other attribute of the segments can be controlled. Although the diameter of the rods or cylinders and the lengths of the segment are typically of nanometric dimensions, the total length is such that, in preferred embodiments, they can be directly visualized in an optical microscope, exploiting the differential refiectivity of the metal components. The particles of this embodiment of the present invention are defined in part by their size and by their existence of at least 2 segments. The length of the particles can be from 10 nm to 50 μm. In preferred embodiments * of the particles is 500 nm - 30 μm in length. In the most preferred embodiments, the length of the particles of this invention is 1-15 μm. The width, or diameter, of the particles of the invention is within the range of 5 nm - 50 μm. In preferred embodiments, the width is 10 nm - 1 μm, and in the most preferred embodiments the width or dimension of the cross section is 30 nm - 500 nm. As discussed above, the particles of the present invention are characterized by the presence of at least two segments. A segment represents a region of the particle that is distinguishable, by any means, from the adjacent regions of the particle. The particle segments bisect the length of the particle to form regions that have the same cross section (generally) and width as the entire particle, while representing a portion of the length of the entire particle. In preferred embodiments of the invention, a segment is composed of different materials from its adjacent segments. However, not every segment needs to be distinguishable from all other segments of the particle. For example, a particle can be composed of 2 types of segments, for example, gold and platinum, having at the same time 10 or even 20 different segments, simply alternating segments of gold and platinum. A particle of the present invention contains at least two segments, and as many as 50. The particles of the invention preferably have from 2 to 30 segments, and more preferably from 3 to 20 segments. The particles may have from 2 to 10 different types of segments, preferably from 2 to 5 different types of segments. A segment of the particle of the present invention is defined to be distinguishable from adjacent segments of the particle. The ability to distinguish between segments includes distinguishing any physical or chemical means of interrogation, including, but not limited to, electromagnetic, magnetic, optical, spectrometric, spectroscopic and mechanical. In certain preferred embodiments of the invention, the interrogation method between segments is optical (refiectivity). The adjacent segments may still be of the same material, as long as they are distinguishable by some means. For example, different phases of the same elemental material, or enantiomers of organic polymeric materials may constitute adjacent segments. Furthermore, it could be considered that a cylinder of a single material falls within the scope of the invention if the segments could be distinguished from others, for example, by functionalization on the surface, or have different diameters. Also particles comprising organic polymeric materials could have segments defined by the inclusion of dyes that would change the relative optical properties of the segments. The composition of the particles of the present invention is best defined by describing the compositions of the segments constituting the particles. A particle can contain segments with extremely different compositions. For example, a particle could be comprised of a segment that is a metal, and a segment that is an organic polymeric material. The segments of the present invention can be comprised of any material. In preferred embodiments of the present invention, the segments comprise a metal (e.g., silver, gold, nickel, palladium, platinum, cobalt, rhodium, iridium); any metal chalcogenide, metal oxide (for example, cupric oxide, titanium dioxide); a metal sulfide, a metal selenide; a metal tellurium; an alloy of metal; metal nitride; a metal phosphide; a metal antimonide; a semiconductor; a semimetal. A segment can also be comprised of an organic mono or bilayer, such as a molecular film. For example, monolayers of organic molecules or controlled, self-contained layers of molecules may be associated with a variety of metal surfaces.

A segment may be comprised of an organic compound or material, or compound or inorganic material or organic polymeric materials, including the long body of mono and copolymers known to those in the art. Biological polymers, such as peptides, oligonucleotides and carbohydrates can also be the main components of a segment. The segments may be comprised of particulate materials, for example, metals, metal oxide or organic particulate materials; or composite materials, for example, metal? oliacr?! amidu, Lir.tL in polymeric material, porous metals. The segments of the particles of the present invention can be comprised of polymeric materials, crystalline or non-crystalline materials, amorphous materials or glasses. The segments can be defined by slits, on the surface of the particle or by the presence of teeth, holes, vesicles, bubbles, pores or tunnels, which may or may not be in contact with the surface of the particle. The segments can also be defined by a change that can be determined in the angle, shape or density of such physical attributes or in the contour of the surface. In embodiments of the invention where the particle is coated, for example, with a polymer or glass, the segment may consist of a gap between other materials. The length of each segment can be from 10 nm to 50 μm. In preferred embodiments, the length of each segment is from 50 nm to 20 μm. The interface between the segments, in certain modalities, need not be perpendicular to the length of the particle or on a uniform or smooth transition line. In addition, in certain embodiments, the composition of a segment can be mixed into the composition of the adjacent segment. For example, between segments of gold and platinum, there may be a region of 5 nm to 5 μm that is comprised of both gold and platinum. This type of transition is acceptable as long as the segments are distinguishable. For any given particle, the segments can be of any length in relation to the length of the segments of the rest of the particle. As described above, the particles of the present invention can have any cross-sectional shape. In preferred embodiments, the particles are generally straight along their longitudinal axis. However, in certain embodiments, the particles may be curved or helical. The ends of the particles of the present invention can be flat, convex or concave. In addition, the ends may be pointed or pointed pencil. The sharp-end modalities of the invention may be preferred when the particles are used in Raman spectroscopy or other applications in which the effects of the energy field are important. The ends of any given particle can be the same or different. Similarly, the contour of the particle can be advantageously selected to contribute to the sensitivity or specificity of the assay (for example, an undulating contour will be expected to increase "repression" of the fluorophores located therethrough).

. . ... . . . "...,." . .. .. .. .. ......,. ^^ .... . ,. . In many embodiments of the invention, an assembly or collection of particles is prepared. In certain embodiments, the members of the assembly are identical, while, in other embodiments, the assembly is comprised of a plurality of different types of particles. In preferred embodiments of the invention, comprising identical particle assemblies, the length of substantially all particles, for particles in the range of 1 μm to 15 μm, can vary up to 50%. The 10 nm long segments will vary ± 5 nm, while the segments in the i μm range can vary up to 50%. The width of all particles can vary substantially between 10 and 100%, preferably less than 50%, more preferably less than 10%. The present invention includes assemblies or collections of nanobar codes composed of a plurality of particles that are distinguishable from each other. The assembly or collection, as used, does not mean that the nanoparticles constituting such assembly or collection are ordered or organized in any particular way. Such assembly is considered to be constituted of a plurality of different types of particle "flavors". In some such assemblies, each of the nanobar codes of the assembly may be functionalized in some way. In many applications, the functionalization is different and specific to the specific flavor of the nanoparticle. The assemblies of the present invention can include from 2 to 1010 different identifiable nanoparticles. Preferred mounts include more than 10, more than 100, more than 1,000, and in some cases more than 10,000 different flavors of nanoparticles. The particles constituting the assemblies or collections of the present invention are segmented in most of the embodiments. However, in certain embodiments of the invention, the particle assembly particles 5 do not necessarily contain a plurality of segments. In certain other embodiments of the invention, the particles of the present invention may include monomolecular layers. Taler, monomolecular layers can be found at the tips or ends of the10 particle, or between segments. Examples of use of intermolecular monomolecular layers are described in the section below entitled ELECTRONIC DlSPOSmvOS, in U.S. Application for Serial No. 09 / 598,395, filed June 20, 2000. The present invention is directed to the manufacture of codes of 15 self-stable nanobars. "Autostable" means that the nanorbar codes that are produced by some form of deposition or growth within a template have been released from the template. Such nanobar codes are typically freely dispersible in a liquid and are not permanently associated with a stationary phase. The nanobar codes that do not 20 are produced by some form of deposition or growth within the template (for example, automotive nanobar codes) can be considered to be self-stable even when they have not been released from a template. u ^ tíí? mtÉ e *? * i? kák * -i? The term "free standing" does not imply that such nanoparticles should be in solution (although they may be) or that nanobar codes can not be attached to, be incorporated into, or be part of a macrostructure. In fact, in certain embodiments of the invention, the nanoparticles can be dispersed in a solution, for example, paint, or incorporated within a polymeric composition. The particles of the present invention can be prepared by a variety of applications. The preferred processes for the manufacture of a particular particle can often be a function of the nature of the segments comprising the particle. In most modalities of the invention, a template or mold is used in which the materials constituting the various segments are introduced. The defined pore materials are the preferred templates for most of the preferred particles of the present invention. Al203 membranes containing pores of consistent size are among the preferred templates, although photolithographically prepared templates, porous polycarbonate membranes, zeolites and block copolymers can also be used. Methods for forming particle segments include electrodeposition, chemical deposition, evaporation, chemical self-assembly, solid-phase manufacturing techniques, photochemical and photolithographic techniques. The chemical self-assembly in a method of forming particles from preformed segments, whereby the segments are derivatives and a chemical reaction between species, in different segments creates a union between segments. The chemically self-contained nanoparticles have a unique ability to be separated in a controlled manner between segments by reversing the process of chemical bond formation. One of the preferred synthetic protocols for preparing metal nanobar codes according to the embodiments of the present invention is an extension of the work of Al-Mawlawi et al. (Al-Mawlawi, D., Liu, C.Z., Moskovits, M.J. Mater.Res. 1994, 2, 1014; Martin, C.R.C.M. Mater. 1996, 8, 1739) on electrochemical synthesis directed at a template. See example 1, below. In this method, metals are deposited electrochemically within a porous membrane. The synthetic method of the present invention differs from previous work in several aspects, including the following. First, the electrodeposition is carried out in an ultrasonication bath. Second, the temperature is controlled, for example, using a recirculating temperature bath. These two first modifications increase the reproducibility and monodispersity of cylinder samples, facilitating the transport of mass of ions and gases through the pores of the membrane. Third, rods with multiple bands are prepared by sequential electrochemical reduction of metal ions (eg, Pt2 +, Au +) with the pores of the membranes. Because the length of these segments can be adjusted by controlling the amount of current that passes through each electrodeposition step, the cylinder resembles a "bar code" at the nanoscale with each segment length (and identity) programmable in advance. Although the width of the cylinders and the segmented lengths are generally of nanometric dimensions, the total length is generally such that it can be visualized directly in an optical microscope, exploiting the differential refiectivity of the metallic components. There are many parameters in the synthesis of nanocylinders that are refinable, so it is theoretically possible to generate many millions of different patterns,; uniquely dentifiable using conventional optical copy. The most important characteristic that can be changed is the composition of the listed cylinders. The simplest form of a nanoparticle is one with only one segment. For this purpose, several different types of these solid bar codes have been prepared. By simply using only a coating solution during the preparation, a solid nanoparticle is produced. To generate nanobar codes of two segments, two metalsSee. (for example Au, Ag, Pd, Cu, etc.) can be electrodeposited sequentially or simultaneously to form alloys. The nanorbar codes can also be generated using 3 different metals. The synthesis of an Au / Pt / Au cylinder can be achieved with 1 C of Au, 8 C of Pt and 1 C of Au. The nominal dimensions of the segments are 1 μm Au, 3 μm Pt, 1 μm Au. The 5-segment nanobar codes, Ag- / Au- / Ag- / Au- / Ag, were generated by electrodeposition of the appropriate metal. In some embodiments it is possible to include all the metals in solution, but to control the deposition by varying the potential current load. A 9-segment nanobar code has also been prepared, Au- / Ag- / Au- / Ag- / Au- / Ag- / Au- / Ag- / Au. The number of segments can be altered to the desired specifications. The next controllable factor is the diameter (sometimes referred to here as the width) of the individual cylinders. Many of the nanobar codes described were synthesized using membranes with a pore diameter of 200 nm. By altering the diameter of the pore, cylinders of different diameter can be produced. The Au cylinders have been synthesized in a membrane having pores with a diameter of 10 nm, pores of 40 nm, and pores in the range of 200 to 300 nm. The ends of the cylinders typically have rounded ends or flat ends. A TEM image of an Au cylinder that is 15 produced by ining the current flow (from a reduction to -0.55 mA / cm2 to an oxidation at +0.55 mA / cm2) and removing some of the gold from the tip of the cylinder generated a tip that extends from the tip of the cylinder. Additionally, branched ends can not be generated. This can be controlled typically by controlling the amount of metal that is electrodeposited in the 20 membrane. The edges of the pores of the membrane have the tendency to be branched, which leads to this type of structure.

An additional way to alter the ends of the cylinders is to control the rate of deposition. The gold cylinders (2 C total, 3 μm) were electrodeposited at a current density of 0.55 mA / cm2. Then the current density was reduced to 0.055 mA / cm2 and 0.1 C 5 of Au was electrodeposited. The last gold segment is deposited in a hollow tube along the walls of the membrane. In Example 1, the manufacturing of unique nanoparticle flavors according to an inion modality is described. To produce many thousands of nanocylinder flavors, in practical quantities, and to bind most or all molecules, novel combined synthesis techniques are necessary. Various embodiments of synthesis are included within the scope of the invention. Each method has advantages and disadvantages depending on the specific application and the required type method and the total number of nanorbars required for the application. The present invention includes methods of manufacturing nanoparticles that allow the simultaneous or parallel manufacture of a plurality of different flavors of nanobar codes. Prior to the present invention, no system or apparatus had been described by which it was possible to prepare more than one type of code of 20 nanobars simultaneously or in parallel. In the preferred embodiments of this invention, such a method of simultaneous manufacture of nanobar codes allows the manufacture of 2 or more, more than 5, more than 10 and preferably more.

'TffñT futrí *' g ^^^ MiU ^ of 25 different flavors of nanobar codes, by simultaneous or parallel means that common elements are used in the manufacture of more than one nanobar code, for example, in the section written in Figures 1 and 2, there are 25 separate membranes, each with a separately controllable electrode connection on the back side, but with common access to the position electrode solution., the separated membranes (or regions in a single membrane) can have a common electrode, but access to the controllable solution separately. In other modalities more, the simultaneous manufacture of different types of nanoparticles is controlled in a common way. Any system or apparatus by which a plurality of different nanoparticle flavors (e.g., particles having a plurality of segments, which are from 10 nm to 50 μm in length, and having a width of 5 nm to 50 μm which are distinguishable from each other) ) can be prepared in parallel is included within the scope of this invention. Among the options that can be used to perform this manufacturing in parallel are the following: 1. Multielectrode or microfluidic synthesis: To synthesize many flavors of nanowire on a single membrane, the membrane can be divided into separate electrical zones, with each zone using a different receptor of elctrodeposición. Of course, several smaller membranes could be used, one for each separate zone, as opposed to a single membrane with multiple zones. The electric zone method can be achieved by taxing the evaporation of Ag that is initially on one side of the membrane on many separate islands. Each separate island would have its own electrode, and the control circuit can activate each island separately for electrodeposition. The microfluidic method - uses a single evaporated Ag electrode, but would divide the opposite side of the membrane into separate fluidized regions, and would control the flow of the electrodeposition solutions of each region. Both of these techniques can be automated, and result in the synthesis of hundreds of nanocylinder membrane flavors. Thousands or millions of flavors will probably not be practical with any of these methods due to practical limitations in the number of electrical or fluidifying connections to the membrane. 2. Embossed front side insulation: This method applies stamped insulating coatings (eg, photoresist) to the front side (electrodeposition side) of a membrane. Where the membrane is coated, the electrodeposition is inhibited. The coating can be removed and reapplied with a different pattern between the electrodeposition steps to achieve the synthesis of many flavors of nano bar codes within a membrane. 3. Stamped back side insulation: This method applies stamped insulating coatings (eg, photo-protection) to the back side (electrode side) of a membrane, which is divided into many separate electrical contacts. Where the electrode is coated, the electrodeposition is inhibited. The coating can be removed and reapplied with different patterns between the electrodeposition steps to achieve the synthesis of nanobar codes inside a membrane. 4. Vertical or horizontal lithography: This technique, which offers greater design flexibility in the size and shape of nanowires, uses lithographic processes to stamp the deposition of multiple layers of metals on a silicone substrate. This method takes advantage of the tremendous capabilities developed in microelectronics and MEMS, and promises very high quality cylinders with greater design flexibility in the size and shape of the nanowears of membrane-based techniques. Each of these synthetic methods must be complemented with good complementary arrangements to allow the release of the nanowire in separate containers. 5. The method of light-steerable position: one more technique that could produce thousands of flavors in a synthesis step also uses membrane-based synthesis, but includes the light-directed control of the electrodeposition process. In this technique, a light-emitting semiconductor device is used to spatially modify the electrical potentials in the vicinity of the membrane, and in this way spatially modulate the electrodeposition currents. In this way the membrane is optically subdivided into many different zones, each of which produces a different nanocylinder flavor. 6. Electrical multiplexing to multiple separate template membranes submerged in common electrodeposition solution: this method, multiple-pattern membranes are immersed in a solution of • common electrodeposition, with a common anodic electrode (platinum). Each 5 membrane has an electrical connection separated from a power source and / or computer controlled voltage to its back side coated with silver.

Several of these modalities are based on ...? or existing buildings using defined pore membranes, (i) The first technique generates hundreds to perhaps a few thousand types of nanocylinders, lithographically modeling the silver on the back side that is deposited on the membrane on isolated islands, each island forming a electric contact individually dirigible. As an example, each island would have enough surface area to contain between 106 and 108 individual cylinders, all of the same type. (Note that post 15 that the thickness of the membrane, and therefore the pore length is much greater than the length of the nanocylinder, multiple nanocylinders can be synthesized in each pore. Each nanocylinder can be separated from the others in the same pore by a silver plug that would later dissolve. This could increase the total throughput in lOx). The membrane is then placed, 20 with careful recording, on a "bed of nails" apparatus, with individual spring loaded bolts in contact with each electrode on the membrane. The computer controlled circuit attached to the nail bed is ^^^^ B ^^ jggj gfa - ^ = ^ able to individually turn on or off each electrode. During the electrodeposition process, each island would be electrodeposited with unique combinations of metal types and thicknesses. In this way, each island would produce cylinders of different length, different numbers of strips, and different combinations of 5 materials, allowing a final design flexibility, (ii) The first method will be limited in the number of types of cylinders that can be synthesized for the reliability and packing density of the nail bed apparatus. To avoid this limitation, the Nail Comma device can be replaced by a liquid metal contact. To prevent the bath from When liquid contacts simultaneously with all the electrodes, the back side of the membrane can be modeled with a non-conductive coating. To individually direct the electrodes during synthesis, the pattern would be removed and replaced between the electrocoating steps. This method will allow a much higher density of isolated islands, and therefore 15 so that more types of cylinders are synthesized. With an island separation of 100 microns, which would be trivial to achieve using lithographic modeling, up to 105 types of cylinders could be synthesized. Since the total number of pores in each membrane is a constant, there will be proportionally fewer cylinders of each type, (iii) The first two methods use membrane filters 20 of commercially available aluminum oxide, which have a pore size and density which are suitable for the synthesis of nanowolders. However, the thickness of the membrane is typically greater than that required, which can cause variability in the lengths of the cylinder in the strip due to uneven mass transport in the pores during electrodeposition. Also, the largest pores available in these membranes (and thus the widths of nanocylinders) are 250 nm, and it would be desirable for some applications to have cylinders with widths of 1 micron or more (this could also be used for modalities with widths less than 1 μm). To solve these problems, pore matrices can be constructed using photolithographic techniques, which will give final control over the pore dimensions and lengths, and will increase the design flexibility and quality of the resulting nanowillers. According to this modality, a plate coated with positive photoprotection is exposed to a pattern of light interference, using a technique similar to that used for diffraction gratings generated by lithography. The plate is typically silicone, with a thin coating of titanium and gold, a thick coating of polymethyl methacrylate (PMMA) 15 and a photoprotection. Two exposures at right angles and the subsequent development produce an array of vertical holes in the photoprotection. Reactive ion etching is then used to transfer the perforated template down through the PMMA layer, which becomes the template. The photoprotective layer is removed, and the gold layer under the PMMA becomes 2 or cathodes for electrodeposition in the PMMA pores. The shape and diameter of the nanocylinders could be adjusted by controlling the light source and the resulting constant wave pattern.

An advantage of this technique is that the thickness of the template, which is the same as the pore length, can be designed to the length of the cylinders, which improves the uniformity of the electrodeposition through the membrane. With this technique, they can be constructed from 1010 to 1012 types of 5 nanocylinders on a single substrate. The two methods described above can be used to synthesize many types of nanobar codes from a single plate, (iv) One more method uses previously defined lithographically-defined pores, and achieves final design flexibility using novel light-directed electrodeposition . The pores of the staff 10 are constructed just as in the third method, but on top of a photosensitive semiconductor plate. The pore side of the plate is immersed in the electrodeposition reagent and, on the other hand, it is illuminated with light patterns. The light exposure is used to generate photocurrent on the plate and activate or deactivate the electrodeposition current for each conductive zone 15 inside the plate. A computer-controlled space light modulator selectively illuminates different zones at different times, so that each zone is subjected to a different computer controlled electrodeposition amount. Depending on the resolution of the optical system that exposes the plate, this would result in 104 to 106 separate flavors of 20 nanocylinders synthesized on a single plate. With 1012 pores in total per plate, they could be synthesized from 106 to 108 nanocylinders of each flavor.

It should be noted that there are numerous other materials that can be used to prepare membranes or templates for the synthesis of nanowolders. An example of many are bundles of optical fibers in which the cores are taxable under conditions where the coating or plating does not. Carrying out this etching, followed by separation through the beam, produces a membrane with orifice diameters the size of the fiber cores. Note that the fibers can be stretched (using heat) to submicron diameters. Note also that fiber bundles :, with collections of more than 1,000,000 fibers are commercially available; this could easily be extended to 10 million. Another group of materials that could be used, for example, are molecular sieve materials with well-defined cavities, such as zeolites. Note also that other methods can be used to prepare templates or membranes from a variety of different methods. Such methods include, but are not limited to: MEMS, electron beam lithography, x-ray lithography, uv lithography, deep lithography, projection lithography, stationary wave lithography, interference lithography and microcontact printing. Self-assembly / chemical disassembly methods can also be used. For example, a two-dimensional, tightly packed, infinite hexagonal layer formation of latex spheres on a flat surface has been demonstrated. Such particles should shrink by 10% of its size, for example, by cooling the temperature. Then a polymer can be grown in the spaces between the infinite 2-D array (which is not already tightly packed). Then the spheres are selectively dissolved, leaving behind a polymeric material with well-defined holes equal to the final diameter of the latex spheres. The particles of the present invention can also be prepared on a large scale by automating the basic electrodeposition process, which was described in Example 1. For example, an apparatus containing a series of membranes and separating the electrodes and producing an ion can be used. Large number of different flavors of nanoparticles in an efficient computer controlled way. An example of this type of apparatus is described in Figures 1 and 2. The embodiment of the invention described in Figures 1 and 2, synthesizes 25 types of nanobar codes simultaneously in 25 membranes. 15 in the form of separate templates (eg Whatman's Anodisc membranes, 25 mm in diameter, 60 microns thick, with 200 nm pores), mounted in a liquid flow cell. Before mounting the membranes in the flow cell, each membrane coated with silver on one side (which is the bifurcated pore side of the membrane) in a vacuum evaporator. TO Subsequently each membrane is immersed in a silver electrodeposition solution with electrodes on both sides, and additional silver is electrodeposited onto the evaporated silver coating and in the pores (at 4 mA during ag? yes ^ approximately 30 minutes), to completely close all the pores of the membrane. Each membrane is then mounted with its silver coated side in contact with an electrode in the flow cell. The flow cell is approximately 1.5 mm thick, with a content of approximately 30 5 ml of liquid. The opposite membrane is a platinum mesh electrode with a slightly larger surface area than the entire 5x5 array of membranes. The flow cell can be filled (by computer control) with water, gaseous nitrogen, gold electrodeposition solution (eg Technics), silver electrodeposition solution (eg Technics Silver Streak and / or electrodeposition solutions) additional). The flow cell is in thermal contact with a cooling water tank, the temperature of which is controlled by recirculation through a temperature controlled bath. In the cooling tank opposite the flow cell, there is an ultrasonic transducer (Crest, 250 Watt), which is switched on 15 during electrodeposition operations to facilitate the transport of mass of ions and gases through the pores of the membrane. Programming and control programming systems are used to automatically flow the appropriate solutions through the flow cell, and the individual control of the electrodeposition currents or potentials in each separate membrane. The 20 programs and programming systems also measure the temperature in various places in the apparatus, and control the sonicator and the peristaltic pump. Programs and programming systems allow the user to define recipes that describe the desired strip pattern for each nanobar code in the 5x5 array. The programs and programming systems read the recipe, and then automatically execute all the fluidic and electrical steps to synthesize different types of nanobar codes in each membrane. After completing the nanocylinder synthesis method, the membranes are removed from the flow cells, and individually post-processed to release the nanobar codes from the pores in the template. First, each membrane is immersed in approximately 2M HN (nitric acid) for approximately 30 minutes to dissolve the subsequent silver coating. Next, the membrane is immersed in NaOH to dissolve the alumina membrane, and release the cylinders in solution. The cylinders or rods are then allowed to settle under gravity, and the NaOH is washed and replaced with H20 or ethanol for storage. In a further embodiment, instead of moving the exposed solution to a stationary template membrane, the movement of the membranes or templates may be from one electrodeposition solution to another. An apparatus for effecting such manufacturing of 25 types of nanobar code flavors is described in Figures 1 and 2. As described above, 25 separate membrane templates are placed in a common solution environment, and the deposition is controlled by the application of current to individual membranes. For example, membranes 1-10 may begin with the deposition of a gold layer that is 50 nm .-fc _ * f-l thickness, the membranes 11-20 can begin with the deposition of gold that is 100 nm thick, while membranes 21-25 may not have an initial layer of gold. This deposition step can easily be effected in the apparatus of this mode, filling the solution reservoir with a gold electrodeposition solution 5, and applying current to the membranes 1-10 for a predetermined period of time, the membranes 11-20 twice not as much as all the membranes 21-25. The gold electrodeposition solution is then removed from the chamber and the chamber is rinsed before introducing the next electrodeposition solution. The apparatus of this mode has been designed to rotate around a pivot point to facilitate access to the solution chamber and electrical and plumbing controls on the back side of the apparatus. Referring to Figure 1, the apparatus rests on a base 101. The turning mechanism is comprised of a rotating support 103, the handle or pin handle 15 for turning immobilization 105, and rotation pin 107. The apparatus is equipped with a halogen light, contained in box 108, and a sonicator, located at 109, in fluid communication with a solution chamber. The flow cell is defined by the rear cell assembly 111 and the front cell assembly 113. The electrical connectors 115 are located 20 on the upper parts of the rear and front assemblies. The mounts are held in place by holding bolts 117 to maintain a sealed solution chamber. The 25 templates 119 for the growth of nanoparticles they are maintained between the front and rear assemblies, and the front assembly has a front window of the electroformation cell 121. Figure 2 is a cross section of the apparatus shown in Figure 1. Many of the same elements that can be observed in the Figure 2 were defined with respect to Figure 1, and have been numbered in a similar manner. Figure 2 also allows the display of cell separation joints 123 between the front and rear assemblies and alignment bolt of the joint 125. Figure 2 also shows the glass window of the rear assembly 127. The water tank 129 for the temperature control is adjacent to the rear mount, and halogen lamp 131. is shown. The ultrasonic apparatus is comprised of the ultrasonic transducer 133 and the ultrasonic tank 135. Although the embodiment described above clearly shows how 25 types of codes can be prepared Nanobars comprising cylindrical metal nanoparticles, segmented by synthesis in parallel, the concept has a wide applicability. It is easy to extend this modality to hundreds or thousands of parallel reaction chambers. Similarly, it is easy to extend this method to the manufacture of nanocylinders with one or more different materials. Likewise, it will be clear, that through the proper use of Ag separators, that more than one flavor of nanobar code can be prepared within a single reaction vessel. In other words, you could prepare an Au-Pt cylinder, deposit Ag, and then prepare a fi-t i-ri f ir-it triiiiitrt - f tJmnfrrr .ffihlllÉr '"• - * - -« - • • - - - • -. - * - *? t? foi? tt * 3 ~? -a ~ M- - ** > »** <» - * L? -i '^ - Au-Pt-Au cylinder. After the release of the cylinder from the membrane, the Ag solution will lead to production Of course, the number of only one type of particle could be increased by growing multiple copies - from a single cylinder in the same reaction vessel - in the same way it will be understood that, instead of introducing a solution From the medium of position to a collection of membranes, it is easy to use microfluidics to produce templates individually.In other words, a different electrodeposition solution could be released simultaneously to two or more places. 5 or 10 or more compositions, and with 5 or 10 or more segment widths, at the same time, but in different prepro places Importantly, the materials chosen for this synthesis (Au, Ag, Pt) are only illustrative, and not limiting. There are numbers or materials that can be electrodeposited in this way, including metals, metal oxides, polymers and so on, which are sensitive to multiplexed synthesis. More generally, multiplexed nanoparticle synthesis does not need to be configured to electrochemical deposition in a host. For example, the materials described here could likewise be prepared by sequential evaporation or sequential chemical reaction. This expands the possibilities of the multiplexed synthesis of nanoparticles to include all oxides, semiconductors and metals. Regardless of the synthetic method used, when the synthesis is carried out on a membrane, a final critical step is required to separate each unique type of nanoparticle and release all the nanoparticles in solution., for surface preparation or denaturation. In the preferred embodiments of the invention this is done by chemical dissolution of the membrane and reinforcing the electrode, using a series of solvents. These solveriits could be acids, bases, organic or aqueous solutions, at one or more temperatures or pressures, with one or more treatment times. Two additional release techniques are: (i) After synthesis, either on the membrane or the flat substrate, matrix separation techniques of the semiconductor industry can be used. The substrate will be coupled to a flexible adhesive material. A cutting saw cuts through the substrate, leaving the adhesive intact. The adhesive is then stretched uniformly to provide physical separation between each island, each of which is then automatically removed by a robot, and placed in a separate microwell. An automated fluidic station is used to introduce the etching solutions needed to free each cylinder towards the solution, (ii) An alternative mode is to couple the microwell substrate containing wells in the same pattern as individual islands in the membrane and to attach the array of channels through which chemical attack solutions flow. The membrane or plate can be walled between the microwell substrate and the channel array. The chemical attack fluid is then introduced into the channels that dissolve the Ag support and carries the nanocylinders to the corresponding well. Other means for removing the particles from the membrane are also possible, including but not limited to laser ablation, heating, cooling and other physical methods. Synthetic techniques directed to the membrane-based template are preferred because they are capable of producing a very large number of very small nanowolders. The electrodeposition conditions can be suitably controlled to produce many types of nanowire bar codes. For applications such as multiplexed immunoassays, where tens to many hundreds of types are required, known techniques are suitable and can simply be scaled to provide the necessary number. For applications such as protein signatures, where dozens are required at many hundreds of types, high performance synthesis techniques and the ability to uniquely identify each of thousands of different barcodes are required.

EXAMPLES The following examples are provided to allow those skilled in the art access to information regarding various modes of .-. ** .. a ajflaah ^ aS jÉj ^ dfc fckj ^^ E, the present invention, and do not intend in any way to limit the scope of the invention.

EXAMPLE 1 One embodiment of the present invention is directed to the synthesis directed to the multi-flavor template of nanobar codes for the purpose of multiplexed assays. For this application it is desirable to construct a variety of different flavors, which are easily distinguished by optical microscopy. For example, 10 different flavors of nanorbar codes were synthesized according to the following table, using silver and gold segments. Note that the description field of the table indicates the composition of each nanobar code by material and length (in microns) of the segment in parentheses. For example, Flavor # 1 is gold with a length of 4 microns, Flavor # 2 is 2 microns of gold, followed by 1 micron of silver, followed by 2 microns of gold.

A detailed description of the synthesis of Taste # 4 is given below. (All other flavors were synthesized by minor and obvious changes to this protocol). We used Whatman Anoporo discs of 25 mm diameter with pores of 200 nm in diameter for the synthesis of nanobar codes directed to the template. Electrochemical metal deposition was carried out using commercially available gold (Technic Orotemp 24), and silver electrodeposition solutions (Technic ACR 1025 SilverStreak Bath). All the electrodeposition steps described below were carried out in an electrochemical cell submerged in a sonication bath, which was controlled at a temperature of 25 ° C. The synthesis of Taste # 4 of the nanobar code was carried out as follows. The membrane was pretreated by evaporating -500 nm of silver on its branched side. To completely fill the pores on this side, about 1 C of silver was electroplated on the evaporated silver, using an electrodeposition current of 1.7 mA for approximately 15 minutes. Then additional 1 C of silver was electrodeposited in the pores of the membrane from the opposite side of the evaporated silver, using an electrodeposition current of 1.7 mA for about 15 minutes. This silver layer was used to fill the "branched pore" region with a thickness of several microns of the membrane. The silver electrodeposition solution was removed by serial dilutions with water, and was replaced by the gold electrodeposition solution. The gold segments of 2 microns in length were then deposited using an electrodeposition current of 1.7 mA for approximately 30 minutes. The gold electrodeposition solution was removed by serial dilutions with water, and was replaced by the silver electrodeposition solution. The silver segment of 2 microns of final length was then deposited using an electrodeposition current of 1.7 mA for approximately 30 minutes. The membrane was removed from the apparatus, and the evaporated silver layer (and silver electrodeposited in the branched pores) was removed by dissolving in 6M nitric acid, taking care to expose only the branched pore side of the membrane to the acid. After this step, the nanobar codes were released from the alumina membrane by dissolving the membrane in 0.5 M NaOH. The resulting suspension of nanobar codes was then centrifuged repeatedly and washed with water.

EXAMPLE 2 An important goal is to demonstrate the ability to use a large number of materials in the nanobar codes of the present invention. To date, cylinder-shaped structures formed by electrochemical deposition in a membrane template (alumina or etched polycarbonate) include Ag, Au, Pt, Pd, Cu, Ni, CdSe, and Co. Primarily, membrane membranes have been used. alumina with a diameter of 200 nm for convenience. Many of the materials are now being used in polycarbonate membranes of smaller diameter. The CdSe is currently electrodeposited via a potential sweeping method of a solution of CdS04 and SeÜ2. Problems of mechanical stability with the metal have been found: the CdSe interface; that is, they break when sonic during the process of removing them from the membrane. This has been remedied with the addition of a 1,6-hexandithiol layer between each surface. Cu and Ni are electrodeposited using the commercially available electrodeposition solution. Working under similar conditions as for the Ag and Au solutions, it was found that these metals are electrodeposited at approximately the same speed, -3 μm / hr. The Co is electrodeposited from a solution of COPS04 / citrate. Those cylinders look like «^ ..» »fili fri -fg * ^^ grow very monodisperse, however, they grow comparatively slowly, -1.5 μm / hr.

EXAMPLE 3 One embodiment of the present invention is directed towards the synthesis directed to the template of nanoscale electronic devices, in particular diodes. One method combines electrochemical electrodeposition of membrane reproduction of metal electrodes in the form of a cylinder with non-electrolytic self-assembly layer by layer of semiconductor / polymer films of nanoparticles sandwiched between the electrodes. The self-assembly of layer by layer layer of T 2 / multilayer polyaniline film on the top of a metal nanowolder within 200 nm pores of an alumina membrane is described below. 1. Materials Whatman Anoporedisks (AI2O3 membranes) with a pore diameter of 200 nm was used for the synthesis of the diode directed to the template. Electrochemical metal deposition was carried out using gold (Technic Orotemp 24), platinum (Technic TP), and commercially available silver electrodeposition solutions. The titanium tetraisopropoxide [Ti (ipro) 4], mercaptoethylamine hydrochloride (MEA), ethyltriethoxysilane, chlorotrimethylsilane were purchased from Aldrich. All reagents were used without major purification. All other chemical compounds were reactive grade and were obtained from commercial sources. The colloidal Ti02 was prepared as follows. Ti (ipro) 4 was dissolved in 2-methoxyethanol under cooling and stirring. The solution was kept under stirring until it became slightly yellow, after which another portion of 2-methoxyethanol containing HCl was added. The molar ratio of the components in the prepared solution was Ti (ipro) 4: HCl: 2-methoxyethanol = 1: 0.2: 20. This solution was diluted with water to adjust the concentration of T02 at 1% and allowed to age for three weeks. The resulting opalescent sol was subjected to rotary evaporation at 60 ° C to give a bright xerogel powder containing 75% (w / w) of titanium. This xerogel was used as a precursor for the preparation of Ti02 aqueous standard sol with a Ti02 concentration of 2.3% by weight (0.29 M) and pH = 3, which was stable for several weeks. XRD investigations of the titania xerogel allowed to estimate the average size of the colloidal anatase crystals at 6 nm, the TEM image of the Ti02 standard sun shows particles of 4 to 13 nm in diameter. The emeraldine (EB) base was also prepared from polyaniline (PAN). A dark blue solution of PAN in dimethyl formamide (0.006% by weight) was used as a standard solution for the synthesis of the film. 2. Synthesis of cylinder-shaped diodes The synthesis of cylinder-shaped diodes was carried out as follows. The metal electrodes were electrochemically grown inside a porous membrane. Briefly, the membrane was pretreated by evaporating -150 nm of silver on its branched side. To completely fill the pores on this side, 1 C of silver was electroplated on the evaporated silver. These "plugs" of Ag were used as foundations on which the lower ele- cc was made electrochemically. The lower gold electrode of the desired length was sonicated electrodeposited. The electrodeposition solution was removed by washing the membrane in water and drying in an Ar flow. The priming of the lower electrode surface with MEA preceded the deposition of the multilayer TÍ02 / PAN film. This was achieved with 24 hours of adsorption of ethanolic MEA solution (5%). The multilayer film was grown by repeating the successive immersion of the membrane in aqueous Ti02 solution and PAN solution in DMF for 1 h. Each adsorption step was followed by removing the excess reagents by rinsing the membrane in several portions of an appropriate solvent (0.01 M aqueous HCl or DMF) for 1 h, and drying in a flow of Ar. Finally, an upper electrode (Ag or Pt) of desired length was electrodeposited in the upper part of the Ti? 2 / PAN multilayer without sonication. Then the evaporated silver, the "plugs" and the alumina membrane were removed by dissolving in 6 M nitric acid and 0.5 M NaOH, respectively. (They were electrodeposited always 2 k i.- t'Áz? í - # • * X¿ * - », | j & AmpFit to 4 C of Au on top of the Ag electrode to prevent dissolution of the latter in nitric acid. Preliminary experiments also showed that the multi-layered TIO2 / PAN film self-assembled on the flat Au (MEA) substrate was not destroyed in 0.5 M NaOH). The diodes in the form of resulting cylinders were repeatedly centrifuged and washed with water. In most of the experiments, the chemical passivation of the pore wall of the AI2O3 membrane was applied using treatments with propionic acid or alkylsilane derivatives. In the latter case, a membrane was successively wetted in absolute ethanol, anhydrous toluene or dichloroethane for 1 h, r which it was immersed in a solution of ethyltriethoxysilane in anhydrous toluene (2.5% by volume) or a solution of chlorotrimethylsilane in • anhydrous dichloroethane (2.5% by volume) for 15 h. The membrane was then soaked successively for 1 h in the appropriate anhydrous solvent, a mixture (1: 1) of the solvent and absolute ethanol, in absolute ethanol, and finally dried in a flow of Ar. So wetting the membranes treated with water revealed hydrophobic properties of their outer surface. The IR transmission spectrum of the membrane treated with ethyltriethoxysilane or propionic acid showed the appearance of weak bands at 2940, 2865, 2800 cm "1, which can be assigned to C-H stretching vibrations of alkyl and alkoxy groups. 3. Characterization ^ ¿T ^ f ** - ** - * - * "* '*' * '• Transmission electron microscope (TEM) images were obtained with JEOL 1200 EXII at 120 kV acceleration voltage and a filament current of 80 mA Optical microscope (OM) images were recorded.The 5 transmission IR spectra were recorded using a CareZeiss Jena Specord M-80 spectrometer.The IV characteristics for the cylinder-shaped diodes were measured in air at room temperature The TEM images of some typical "in band" bimetallic Au / Pt / Au nanocylinders, which grew electrochemically within the porous alumina membrane, showed that the two ends of the cylinder differed in their topography - one end of the cylinder appeared to be bulging or rounded, while the other end had a hollow appearance in the middle part.Such differences in the appearance of the end of the cylinder could be explained by the adsorption of some amount of ions Metals on the walls of the pore promoting the growth of the metal (for example Ag) in the space of the nearby wall and producing the hollow formation in the middle pore space. During the electrodeposition of a second "band" of metal (e.g., Au), the growth of the metal follows the surface of the bottom cylinder and fills the gap, thereby forming the rounded end. The further growth of the cylinder results in a cup-like end due to the adsorption of metal on the pore walls. ftfcfa ft. »\? ? A ^? &? _ _ _.

Each segment of sequential metal grows in the same way at the end of the underlying segment. It is unlikely that the relatively rough surface of the upper end of a cylinder can be completely covered with the ultra-thin TiO2 / PAN film, thereby preventing the immediate contacts between the lower and upper metal electrodes. From preliminary experiments on flat Au substrates, it was found that multilayer films of TÍO2 / PAN grow on smoother surfaces, demonstrating a better reproducibility in their rectifying behavior. Passivation (hydrophobicization) of the finished surface in AI2O3 of the pore walls with propionic acid or alkylsilane derivatives, such as ethyltriethoxysilane or chlorotrimethylsilane was attempted to smooth the end surface of the upper cylinder, reducing the adsorption of metal on the walls of the cylinder. pore. It can also be expected that the hydrophobicization of the pore walls prevents the Ti02 particles from being adsorbed on the surface of the wall rather than on the surface of the metal electrode located at the depth (-65 nm) of the pore. It was shown that the Ti02 particles easily formed a densely packaged layer on a flat AI / AI2O3 substrate. A higher resolution image typical of the top of the cylinder confirmed that cup-like ends are located on top of the cylinders, and showed that passivation of the wall to some degree results in smoothing of the surface of the ends of the cylinder.

An optical micrograph of the cylinders of Au / (Ti? 2 / PAN)? 0 / Ag / Au, prepared using the membrane derived with ethyltriethoxysilane, showed nanoclinders of uniform length, in which the silver segments are clearly observed between two extremes of gold. TEM images of such a cylinder, recorded in the first several seconds, revealed no visible signs of a metal / film / metal heterojunction within the cylinder. However, after focusing the electron beam on this cylinder for some time (typically dozens of seconds), a fracture appeared in the cylinder and the metal segments were separated, due to the metal fusion induced by the beam, in the vicinity of the Heterounion Au / film / Ag. In TEM images of higher resolution of this fracture, particles of 5 to 10 nm in diameter were observed, which adhere to both ends of the metal. Apparently, the TiO2 nanoparticles are present between two electrodeposited metals. OM and TEM data suggest that automating the multilayer Ti? 2 / PAN film on the upper part of the Au cylinder can be done within the pores of the membrane, and that the self-sealing film does not prevent electrodeposition of the cylinder. Ag on top of the film. It should be noted that TEM images in all probability do not give a true image of the TIO2 / PAN multilayer film inside the cylinder due to the high probability of mechanical destruction of the film while separating the partially molten metal cylinder ends. Long-term exposure of the cylinders to the electron beam results in the complete destruction of the heterojunction and gives rise to two individual nanocylinders with nanoparticles attached at their ends. To investigate the multilayer TÍ02 / PAN film sandwiched between Au and Ag cylinders, Au / (Ti? 2 / PAN) 6 / Ag nanowires were prepared and their 5 Ag electrode from the top was dissolved in nitric acid. The remaining 2C Au cylinders with the film (Ti? 2 / PAN) 6 deposited on top were analyzed by TEM. Preliminary studies showed that the ellipsometric thickness of the multi-layered Ti02 / PAN film self-assembled on the flat Au (MEA) substrate did not decrease after immersion in 6 M HN03 for 30 min., Suggesting stability of the film in the acid medium . In addition, similarly to the Au / (TiO2 / PAN)? 0 / Ag / Au cylinders described above, the TEM image of the Au / (Ti? 2 / PAN) 6 cylinder taken in the first several seconds did not reveal no particle. However, during the prolonged exposure to the electron beam, the gold melted revealing a 15 nanoparticle film on the top of the cylinder. It can be seen that the line of the upper contour of the film is very close to the Au cylinder before the fusion. This fact is consistent with the upper part in the form of cups of the metal cylinders. The multilayer film grows on the surface of the bottom of the cup and the walls of the cup and retains approximately the 20 shape of cups after the thin walls have melted. This explanation is consistent with the observed film height of -100 nm, which allows to better estimate the depth of the gold cup than the thickness of the film (Ti? 2 / PAN) 6. The ellipsometric thickness of the film (Ti? 2 / PAN) 6 I ** "automonted on the Au substrate (MEA) plane was estimated at approximately 10 nm. Characteristic IV of the cylinder-shaped device of 5 Pt / (Ti? 2 / PAN) 3Ti02 / Au revealed a common rectifying behavior. The activation potentials of forward and backward deviation are -0.2 and -0.9 V, respectively.It is noted that in relation to this date, the best method known by the applicant to carry out said invention is which is clear from the present description of the invention.

Claims

REIVIN PICIO NES Having described the invention as above, the content of the following claims is claimed as property. 1. A method for the manufacture of a self-stable segmented nanoparticle, by depositing a plurality of materials within a template, characterized in that it comprises: a) producing the deposition of a first material in the pores of the template; b) produce the deposition of a second material in the pores of the template; and c) releasing the segmented nanoparticles from the template. 2. The method according to claim 1, characterized in that the segmented nanoparticle has a length of 10 nm at 50 μm, and the width of the nanoparticle is from 5 nm to 50 μm. The method according to claim 2, characterized in that the segmented nanoparticle is comprised of 2-50 segments, where the length of the particle is 1-15 μm, the width of the nanoparticle is 30 nm to 2 μm, and the length of the segments is from 50 nm to 15 μm. 4. The method according to claim 1, characterized in that the first and second materials are selected from a group consisting of a metal, a metal chalcogenide, a metal oxide, a metal sulfide, a metal selenide, a metal tellurium, a metal alloy, a metal nitride, a metal phosphide, a metal antimony, a semiconductor, a semimetal, a compound or organic material, a compound or inorganic material, a particulate layer of material and a material compound. 5. The method according to claim 1, characterized in that the first and second materials is a metal. 6. The method according to claim 5, characterized in that the metal is selected from the group consisting of: silver, gold, copper, nickel, palladium, platinum, cobalt, rhodium and iridium. The method according to claim 1, characterized in that the template is selected from the group consisting of an AI2O3 membrane, a photolithographically prepared template, a porous polycarbonate membrane, a zeolite and a block copolymer. 8. The method according to claim 1, characterized in that the deposition of the first or second material is effected by electrochemical deposition. The method according to claim 8, characterized in that an electrode is placed on or near a surface of the template, and the template is placed in contact with a first electrodeposition solution for depositing the first material, and is placed in contact with a second electrodeposition solution to deposit the second material. 10. A method for the manufacture of a nanoparticle by electrochemical deposition of a metal within a template, characterized in that it comprises: a) placing an electrode on or near a surface of the template; b) placing the template in contact with an electrodeposition solution; c) applying an electric current to the solution to produce the electrochemical deposition of the metal in the pores of the template; where the solution is stirred and maintained at a controlled temperature. The method according to claim 10, characterized in that the segmented nanoparticle has a length of 10 nm to 50 μm, and the width of the nanoparticle is 5 nm to 50 μm. The method according to claim 11, characterized in that the segmented nanoparticle is comprised of 2-50 segments, where the length of the particle is 1-15 μm, the width of the nanoparticle is 30 nm to 2 μm, and the length of the segments is from 50 nm to 15 μm. The method according to claim 10, characterized in that the metal is selected from the group consisting of: silver, gold, copper, nickel, palladium, platinum, cobalt, rhodium and iridium. 14. The method according to claim 10, characterized in that the template is selected from the group consisting of an AI2O3 membrane, a photolithographically prepared template, a porous polycarbonate membrane, a zeolite and a block copolymer. 15. A method for the simultaneous manufacture of a plurality of different types of nanoparticles segmented by the deposition of a plurality of materials within a plurality of templates, characterized in that it comprises: producing the first deposition of the first material in the pores of all or some of the templates; produce the second deposition of a second material in the pores of all or some of the templates; and means of control to determine if and to what degree a first or second deposition occurs in a specific template according to pre-selected values. The method according to claim 15, characterized in that it also comprises the step of: releasing the segmented nanoparticles from the templates. 17. The method according to claim 15, characterized in that the segmented nanoparticle has a length of 10 nm at 50 μm, and the width of the nanoparticle is from 5 nm to 50 μm. íti, A'kk.á ,? A.:,i.i.,,,,,,,,,,,,. 18. The method according to claim 17, characterized in that the segmented nanoparticle is comprised of 2-50 segments, where the length of the particle is 1-15 μm, the width of the nanoparticle is 30 nm to 2 μm, and the The length of the segments is from 50 nm to 15 μm. The method according to claim 15, characterized in that the materials are selected from a group consisting of a metal, a metal chalcogenide, a metal oxide, a metal sulfide, a metal selenide, a metal telluride , a metal alloy, a metal nitride, a metal phosphide, a metal antimonide, a semiconductor, a semimetal, an organic compound or material, an inorganic compound or material, a particulate layer of material and a composite material. 20. The method according to claim 15, characterized in that the first and second materials are a metal. The method according to claim 21, characterized in that the metal is selected from the group consisting of: silver, gold, copper, nickel, palladium, platinum, cobalt, rhodium and iridium. 22. The method according to claim 15, characterized in that the template is selected from the group consisting of an AI2O3 membrane, a photolithographically prepared template, a porous polycarbonate membrane, a zeolite and a block copolymer. ? Mti?. * T ?? k ?? Íl 23. The method according to claim 15, characterized in that the deposition of the first or second materials is effected by electrochemical deposition. 24. The method according to claim 23, characterized in that an electrode is placed on or near a surface of the templates, and the templates are placed in contact with a first electrodeposition solution for depositing the first material on all or some of the the templates, and is placed in contact with a second electrodeposition solution to deposit the second material on all or some of the templates. 25. An apparatus for the manufacture of a nanoparticle, characterized in that it comprises: an electrodeposition solution chamber; a template of defined pore size; means for applying a current to produce electrochemical electrodeposition within the pores of the template; means for stirring the solution within the electrodeposition solution chamber; and means for controlling the temperature of the electrodeposition solution chamber. 26. The method according to claim 25, characterized in that the template is selected from the group consisting of a A & amp; & M. > AI2O3 membrane, a photolithographically prepared template, a porous polycarbonate membrane, a zeolite and a block copolymer. 27. An apparatus for the simultaneous manufacture of a plurality of different types of nanobar codes, characterized in that it comprises: an electrodeposition solution chamber; a plurality of templates or a template with a plurality of regions; means for selectively applying an electric current to the regions of the templates; and control means to control whether and to what degree the deposition will occur. 28. The method according to claim 27, characterized in that the template is selected from the group consisting of an AI2O3 membrane, a photolithographically prepared template, a porous polycarbonate membrane, a zeolite and a block copolymer. 29. An apparatus for the simultaneous manufacture of a plurality of different types of nanoparticle codes, characterized in that it comprises: identifying the size, shape and composition of each type of nanoparticle to be manufactured; control the simultaneous production of nanoparticles so that each type of nanoparticles is prepared in a different place. 30. The method according to claim 29, characterized in that the nanoparticles are segmented. 31. The method according to claim 30, characterized in that the segmented nanoparticles are comprised of a 5 plurality of materials. The method according to claim 31, characterized in that the materials are selected from a group consisting of a metal, a metal caycogenide, a metal oxide, a metal sulfide, a metal selenide, a metal telluride. , a metal alloy, a metal nitride, a metal phosphide, a metal antimonide, a semiconductor, a semimetal, a compound or organic material, a compound or inorganic material, a particulate layer of material and a composite material. 33. The method according to claim 32, characterized in that the first and second materials is a metal. 34. The method according to claim 33, characterized in that the metal is selected from the group consisting of: silver, gold, copper, nickel, palladium, platinum, cobalt, rhodium and iridium. 35. The method according to claim 30, characterized in that the segmented nanoparticle has a length of 10 nm at 20 50 μm, and the width of the nanoparticle is from 5 nm to 50 μm. 36. The method according to claim 35, characterized in that the segmented nanoparticle is comprised of 2-50. segments, where the length of the particle is 1-15 μm, the width of the nanoparticle is 30 nm to 2 μm, and the length of the segments is 50 nm to 50 μm.