Abstract:
The manipulation of nanoparticles is facilitated through the use of a Langmuir-Blodgett trough constraining the nanoparticles to two dimensions and allowing their density to be controlled through the barriers of the Langmuir-Blodgett trough. A film formed in this manner can be applied to enhance a transparent conductive electrode on the photovoltaic cell. Alternatively the nanoparticles as so constrained can be given two types of functionalization, for example, of an anticancer agent and a targeting ligand.

Description:
CROSS REFERENCE TO RELATED APPLICATION 
       [0001]    This application claims the benefit of U.S. provisional application 62/099,758 filed Jan. 5, 2015, and hereby incorporated, in its entirety by reference. 
     
    
     BACKGROUND OF THE INVENTION 
       [0002]    The present invention relates to a method of processing nanoparticles for use in multiple applications. 
         [0003]    Recent decades have brought about reliable, methods for the synthesis and functionalization of metal nanoparticles but applying these nanoparticles to many important applications has been hindered by the difficulty of organizing the particles into regular structures with controlled interparticle spacing, for example, as needed to optimize electronic conductivity. Similarly, precise interparticle spacing can be important to control the optical transport properties of these nanoparticles. 
         [0004]    It is generally known to functionalize nanoparticles for the purpose of applying a targeting ligand to the nanoparticles encouraging accumulation of the nanoparticles, for example, in a tumor. The nanoparticles may then serve, for example, as selective absorbers of radiation (for example, microwave radiation) for hyperthermic treatments. 
       SUMMARY OF THE INVENTION 
       [0005]    The present invention provides: (1) a method of constructing films of nanoparticles with controlled interparticle spacing for incorporation into structures such as solar cells and (2) a method of restraining nanoparticles for sophisticated functionalization, for example, using two different functionalizing agents of an anticancer agent and a targeting agent on each nanoparticle so that nanoparticles can be delivered to a tumor site with an anticancer agent that may be activated by heat from the nanoparticles. 
         [0006]    These particular objects and advantages may apply to only some embodiments falling within the claims and thus do not define the scope of the invention. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0007]      FIG. 1  is a flowchart and associated diagram showing the fabrication of a transparent conductive oxide solar cell augmented with gold nanoparticles; 
           [0008]      FIGS. 2 a - c    are representations of functionalized gold nanoparticles on an air water interface (shown in cross-sectional elevation), the nanoparticles functionalized for cross-linking to limit diffusion and rotation; 
           [0009]      FIG. 3  is a figure similar to that of  FIG. 2  showing introduction of a water-soluble functional group to only one side of the immobilized nanoparticles; 
           [0010]      FIG. 4  shows bi-functionalized nanoparticles such as may provide for both an anticancer agent and a targeting agent. 
       
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT 
     Photovoltaic Cell 
       [0011]    Referring now to  FIG. 1 , a process  10  for fabrication of photocells ma provide for the construction of a solar cell substrate  12  per process block  14 , for example, including assembling in parallel adjacent layers of dissimilarly doped semiconductor elements  16  and  18  forming a PN junction. 
         [0012]    In parallel with the above process and possibly in a different facility that does not need traditional integrated circuit processing technologies and which would not suffer from contamination problems caused by nano conductors, a nanoparticle film  20  may be fabricated as indicated by process block  17 . This film  20  may be fabricated, for example, through the use of a Langmuir trough  22  of the type having a tray holding water  24  on whose surface functionalized hydrophobic nanoparticles  26  may be introduced, for example, in a solution of hexanes to arrange themselves along an air water interface  28 . 
         [0013]    Nanoparticles  26 , fur example, may be gold nanoparticles functionalized with thiols, for example, providing the hydrophobic property. The nanoparticles  26  may have a size varying from 3 to 8 nanometers and may be synthesized using a Brust synthesis. Purification to eliminate excess thiols and phase transfer reagents is performed using the Soxhlet extraction technique. 
         [0014]    Barriers  30  on the trough  22  corralling the nanoparticles  26  along the surface of the water  24  may then be isometrically contracted together to compress the nanoparticles  26  into a desired film having a controlled average interparticle spacing and cross-linking agents such as a dithiol or bisdithiol or mixture of the same (and alternatively possibly being diphosphines or diamines) may then be introduced to form cross-links between the nanoparticles  26  connecting them into a robust monolayer  34 . An upper or lower surface of the monolayer  34  may then be modified to make it hydrophilic as will be discussed below, with the cross-linking preventing diffusion of the nanoparticles  26  into the water  24 . 
         [0015]    The solar cell substrate  12 , for example, having an outer surface of silicon oxide or silicon nitride, can be drawn through the monolayer  34  which then adheres to the broad faces of the substrate  32 , utilizing the Langmuir-Blodgett method of monolayer transfer to a solid substrate. For example when the lower surface of the monolayer  34  is made hydrophilic, when the substrate  32  is drawn vertically out of the water  24  through the air water interface  28  a monolayer  34  will be deposited and adhered on its opposite surfaces. During this withdrawal, the barriers  30  may be moved together to preserve the desired density of nanoparticles  26 . Conversely, the upper surface of the monolayer  34  may be made hydrophilic and the substrate passed vertically downward through the air water interface  28 . The result is a thin film with a controlled spacing of nanoparticles  26  adhered to the upper surface of the substrate  12  opposite the backer electrode  21 . The same result may also be achieved using a Langmuir-Schaffer transfer, by which a substrate is oriented parallel to the air-water interface, lowered until contact is made, and then withdrawn from the interface, leaving the hydrohphilic side of the film bonded to the substrate. 
         [0016]    At process block  38 , a layer of a transparent conductive oxide  40  (for example, indium tin oxide) may be sputtered over the nanoparticles  26  to provide a composite conductive electrode  42  on opposite sides of the solar cell substrate  12  for collection of electrical current and the driving of a load. The gold nanoparticles  26  provide improved capture of light energy either by absorption and retransmission or internal reflection. A gram of gold nanoparticles can provide coating for 4000 square meters of transparent conductive oxide. Alternatively, the crosslinked film of gold nanoparticles may be applied to a previously constructed solar cell, where the film would prevent captured light from escaping the cell, thus increasing the dwell time of the incoming radiation and in turn increasing photocarrier generation. 
       Drug Delivery System 
       [0017]    Referring now to  FIGS. 2 a   - c,  thiol functionalized gold nanoparticles  26  in the Langmuir-Blodgett trough  22  described above may be compressed together to get the desired separation as indicated by  FIG. 2 . The thiol functionalization  27 . as discussed above, provides a hydrophobic quality to the gold nanoparticles  26  causing them to align along the air water interface. The nanoparticles  26  may be compressed to desired density using the barriers  30  (shown in  FIG. 1 ) and joined into a monolayer  34  with a cross-linking agent  29  being for example a dithiol or bisdithiol or combination for example as described in paper [1] cited below and hereby incorporated by reference. The cross-linking agent  29  may be introduced in a layer of chloroform (CHCl 3 ) may be applied over the water  24  (as shown in.  FIG. 2 b   ) and then allowed to evaporate as shown in  FIG. 2 c    to promote a cross-linking of the spaced nanoparticles  26 . A polar peptide on the cross-linking agent  29  helps the agent lie flat on the surface of the water  24 . This cross-linking provides two benefits of restricting rotation of the nanoparticles  26  and preventing their diffusion into the water  24  as would otherwise occur when there hydrophobic nature is modified by a ligand exchange process discussed below. 
         [0018]    Referring now to  FIG. 3 , after this cross-linking, new functionalization groups  51  can be introduced into the water  24  in contact with the previous functionalization of the nanoparticles  26  with the thiol functionalization to provide an exchange of ligands. For example, an ethanolic solution of mercaptohexanoic acid can be injected into the aqueous sub phase (the water  24 ) and the excess mercaptohexanoic acid will displace the short chain alkanethiol via a ligand exchange process to provide for asymmetric functionalization of each nanoparticle  26 . This particular ligand exchange provides a hydrophilic surface to the monolayer  34 . 
         [0019]    Conversely, the distal ends of the upper thiol functionalization of each nanoparticle  26  may be modified by through the introduction of a carrier fluid  54  (for example hexanes) over the surface of the water  24  providing a layer immiscible with the water  34  but acting as a solvent to hold the ligands for exchange with the upper thiol functionalization. Generally, the carrier fluid  54  is selected to be non-soluble in the water  24  but to provide a solvent for the desired ligand for exchange. 
         [0020]    Referring now to  FIG. 4 , this regioselective ligand exchange process may be used to produce a so-called Janus nanoparticle  52  having different sides with different functionalizations R 1  and R 2 . In one case, one functionalization may provide for a hydrophilic side to the monofilm  34  for attachment to the substrate  12  discussed above. 
         [0021]    Alternatively, one functionalization (R 1 ) may provide for an anticancer agent that works in conjunction with hyperthermia treatment made possible using the nanoparticle  26  and the other functionalization (R 2 ) may be a targeting ligand allowing the Janus nanoparticles  52  to be preferentially retained in a tumor  56  where the anticancer agent and heat therapy may be delivered. 
         [0022]    Referring again to  FIG. 3 , for this latter purpose, a photo-cleavable cross-linking element  60  may be incorporated into the cross-linking between nanoparticles  26  to allow individual nanoparticles  26  to be extracted by light exposure. For example the photo-cleavable cross-linking element  60  may be nitrobenzyl photo-cleavable linker introduced in the hydrocarbon chain between the sulfur groups of the cross-linking agent  29 . 
         [0023]    These techniques can be extended to arrays of anisotropic nanomaterials such as nanorods, whose optical properties are expected to be dependent upon final orientation (either side-by-side or end--to-end) of the finished crosslinked composition. It will be generally understood that various techniques can be applied to the gold nanoparticles  26  to improve their ability to absorb radiation and in particular lower frequency microwave radiation as opposed to visible light radiation. These techniques increase the electrical size of the nanoparticles  26  for example through the use of a shell structure (nano shell). 
         [0024]    The present application hereby incorporates the following materials in their entirety by reference:
       [1] Langmuir isotherms of flexible, covalently crosslinked gold nanoparticle networks: Increased collapse pressures of membrane-like structures by Tayo A. Sanders II, Mariah N. Sauceda, Jennifer A. Dahl Materials Letters 04/2014; 120:159-162. DOI: 10.1016/j.matlet.2014.01.056; and   [2] Microwave synthesis of a bimodal mixture of triangular plate and spheroidal silver nanoparticles by Anneliese E. Laskowski Daniel A. Decato Mitchel S. Strandwitz Jennifer A. Dahl MRS Communications, 05/2015; 5(2):1-7. DOI: 10.1557/mrc.2015.23.       
 
         [0027]    Certain terminology is used herein for purposes of reference only, and thus is not intended to be limiting. For example, terms such as “upper”, “lower”, “above”, and “below” refer to directions in the drawings to which reference is made. Terms such as “front”, “back”, “rear”, “bottom” and “side”, describe the orientation of portions of the component within a consistent but arbitrary frame of reference which is made clear by reference to the text and the associated drawings describing the component under discussion. Such terminology may include the words specifically mentioned above, derivatives thereof, and words of similar import. Similarly, the terms “first”, “second” and other such numerical terms referring to structures do not imply a sequence or order unless clearly indicated by the context. 
         [0028]    When introducing elements or features of the present disclosure and the exemplary embodiments, the articles “a”, “an”, “the” and “said” are intended, to mean that there are one or more of such elements or features. The terms “comprising”, “including” and “having” are intended to be inclusive and mean that there may be additional elements or features other than those specifically noted. It is further to be understood that the method steps, processes, and operations described herein are not to be construed as necessarily requiring their performance in the particular order discussed or illustrated, unless specifically identified as an order of performance. It is also to be understood that additional or alternative steps may be employed. 
         [0029]    It is specifically intended that the present invention not be limited to the embodiments and illustrations contained herein and the claims should be understood to include modified forms of those embodiments including portions of the embodiments and combinations of elements of different embodiments as come within the scope of the following claims. All of the publications described herein, including patents and non-patent publications, are hereby incorporated herein by reference in their entireties.