Abstract:
A method, apparatus, and system for characterizing thin film materials. The method, apparatus, and system includes a container for receiving a starting material, applying a gravitational force, a magnetic force, and an electric force or combinations thereof to at least the starting material, forming a thin film material, sensing an NMR signal from the thin film material and analyzing the NMR signal to characterize the thin film of material.

Description:
CROSS-REFERENCE TO RELATED PATENT APPLICATIONS  
       [0001]     This application claims the benefit under 35 USC 119(e) of U.S. Application 60/719,479, filed Sep. 22, 2005, incorporated herein by reference in its entirety. 
     
    
     GOVERNMENT INTEREST  
       [0002]     The United States Government has certain rights in the invention pursuant to Contract No. W-31-109-ENG-38 between the U.S. Department of Energy and the University of Chicago operating Argonne National Laboratory. 
     
    
       [0003]     The present invention is related generally to use of nuclear magnetic-resonance (NMR) to characterize thin films. In particular, thin films prepared by use of molecule subcomponents result in tailored films which can benefit from careful control of the assembly process by use of NMR spectroscopy and imaging.  
       BACKGROUND OF THE INVENTION  
       [0004]     The tailored assembly of molecules by use of new methods, such as application of gravitational, magnetic and electric field forces can result in whole new classes of thin films with a variety of important uses. Thus, it is important to be able to characterize the starting components, intermediate and final components, as well as location of molecular assemblages on the substrate; but virtually no methods allow adequate characterization of such assemblages, especially throughout the complex process of fabrication. Moreover, there is a substantial need for comparison of theoretical model assemblies with actual experimental data so as to control and characterize thin film structures generally.  
       SUMMARY OF THE INVENTION  
       [0005]     NMR spectroscopy and imaging is used to carry out detailed chemical and macroscopic structural characterization of thin films. In one system a cylindrical device allows receiving a starting layer of molecules which can be characterized and compared with theoretical NMR spectra. Throughout the process of assembling molecules in a layer, the NMR method can be used to carry out such comparisons with theory as well as perform fundamental chemical characterization, film thickness measurements, and evaluate other macroscopic features, such as characterizing the layering of different chemical components and obtaining dynamical information about the chemical and molecular constituents. Consequently, NMR can perform characterization of the materials and also enable control of the preparation of a desired film product.  
         [0006]     Various aspects, features and advantages of the invention as described hereinafter, and these and other improvements will be described in more detail below, including the drawings as described below. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0007]      FIG. 1  illustrates an example of a device for preparation and NMR analysis of a tailored thin film;  
         [0008]      FIG. 2A  illustrates a thin cylinder film and inclined magnetic field;  FIG. 2B  illustrates a cylindrical shell cross-section and  FIG. 2C  illustrates a chemical shift NMR spectrum for a thin film on a cylinder;  
         [0009]      FIG. 3A  illustrates a cylindrical cross-section of a thin film with differing local magnetic environments for the same chemical constituents around the cross section;  FIG. 3B  shows an NMR spectrum with different chemical shifts for the same chemical constituents being separable;  FIG. 3C  illustrates the thickness of a manufactured film;  FIG. 3D  shows two different NMR spectra corresponding to two films having different thickness;  FIG. 3E  shows application of a magnetic field at an angle to a thin film; and  FIG. 3F  shows comparative NMR spectra for two different angles of magnetic field incidence;  
         [0010]      FIG. 4A  shows a series of NMR spectra for different spinning conditions of the cylinder of  FIG. 1 ;  FIG. 4B  illustrates a free-standing cylinder support film disposed on an extraction rod with a front perspective view of the film removed from the cylinder; and  FIG. 4C  illustrates a polyethylene glycol (PEG) film disposed on an inner surface of the cylinder;  
         [0011]      FIG. 5A  shows simulated NMR spectra for nonadecane of various film thicknesses and  FIG. 5B  shows experimental NMR spectra compared to the simulated results;  
         [0012]      FIG. 6A  shows a static NMR spectrum of a film after spinning in the cylinder of  FIG. 1  for a mixture of nonadecane and PEG;  FIG. 6B  shows an experimental NMR spectrum for a nonadecane film;  FIG. 6C  shows an experimental NMR spectrum for a PEG film;  FIG. 6D  shows a scaled 50:50 sum NMR spectrum of a film of nonadecane and PEG; and  FIG. 6E  shows a 30:70 sum NMR spectrum of a film of nonadecane and PEG;  
         [0013]      FIG. 7A  shows a schematic of a PEG-distearate molecule;  FIG. 7B  shows a magic angle spinning (MAS) NMR spectrum for PEG-distearate;  FIG. 7C  shows a static NMR spectrum for of a film of PEG-distearate;  FIG. 7D  shows a simulation NMR spectrum of a film from adding scaled static NMR spectra of methylene groups from nonadecane and PEG films; and  FIG. 7E  shows a simulated static NMR spectrum of a film obtained from a theoretical expression of the induced magnetic field, B ind ;  
         [0014]      FIG. 8  illustrate a form of the device of  FIG. 1  but including various detectors for monitoring film formation;  
         [0015]      FIG. 9A  illustrates a double-layered polydimethyl siloxane (PDS) and PEG film shown as topographical thickness at a particular radial position of a layer disposed on a cylinder;  FIG. 9B  illustrates a triple-layered film illustrated as a two-dimensional topograph; and  FIG. 9C  illustrates the three-layer film as a three-dimensional topograph;  
         [0016]      FIG. 10A  illustrates a static NMR spectrum of a film taken after shut-down of cylinder spinning;  FIG. 10B  shows the same material of  FIG. 10A  after a rheology relaxation time of 16 seconds; and  FIG. 10C  illustrates the same material of  FIG. 10A  after a rheology relaxation time of 8.27 minutes;  
         [0017]      FIG. 11  illustrates a plot of the maximum NMR intensity as a function of rheology relaxation time after ceasing cylinder spinning;  
         [0018]      FIG. 12  shows a multilayer pharmaceutical in a cylinder shape; and  
         [0019]      FIG. 13  shows a series of NMR spectra of a cylinder film spinning at different speeds. 
     
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS  
       [0020]     A method of thin film characterization involving NMR spectroscopy can be used to perform measurements heretofore unavailable. In preparation of thin films, such as the development of the tailoring of molecular assemblages, it has become necessary to control aspects of preparation. Such features include tailoring as well as characterization of starting, intermediate and finished product chemical features, including macroscopic aspects such as film thickness, orientation, and the location of particular film components in space.  
         [0021]     Using the example device  10  shown in  FIG. 1 , the method of characterization of the products of the method and apparatus can be illustrated. The device  10  is, of course, only one example of use for film preparation; and the method and system described herein is applicable to any film for which characterization is sought. In the device  10  of  FIG. 1 a  gravitational field force, G; magnetic field force, B; and electric field force, E, are shown. Note that the E field force can be parallel or perpendicular (or combinations thereof) to a rotor axis  14  (denoted central axis conductor  42  within the spinning cylinder  12  as in  FIG. 1  and  FIG. 8 ). A radial electric field E is generated by power source  19 . The G field force can perform separations as well by molecule mass, such as for films with slightly different density. We can therefore, for example, fabricate a film with holes and then put molecules through the holes in the film because of the separability of different densities and/or of different sizes of molecules which can be inserted there through.  
         [0022]      FIG. 2A  illustrates a thin cylinder film with long axis Z inclined at an angle β with respect to magnetic field B 0 .  FIG. 2B  illustrates the cross-section of a cylindrical film  20  with labels indicating permeabilities (μ) for spinning cylinder  12  (μ 3 ), cylindrical film  20  (μ 2 ), and interior (μ 1 ) and exterior (μ 4 ) air regions.  FIG. 2C  illustrates a chemical shift NMR spectrum for the thin film  20  on the interior of cylinder  12 .  
         [0023]     As shown in  FIGS. 3A-3F , the environmental (“chemical”) shift of the NMR resonance depends on the permeability (μ) of the thin film  20 , the material that surrounds the film  20 , and on the macroscopic geometry of the film  20  with the NMR peak shape (obtained using NMR device  22 ) containing information about how the induced magnetic field changes with angle Ø, angle β, permeabilities (μ) and nuclear shielding parameters (σ):  
               B   ind     =         B   0     ·     {     1   -       1   2     ⁢     (       μ   2     -     μ   4       )       -         a   2   2       2   ⁢     r   2         ⁢     (       μ   2     -     μ   1       )     ⁢   cos   ⁢           ⁢   2   ⁢   ϕ       }     ·     {     1   -     [         (       σ   xx     -     σ   i       )     ⁢     cos   2     ⁢   ϕ     +       (       σ   yy     -     σ   i       )     ⁢     sin   2     ⁢   ϕ     +       (         σ   xy     +     σ   yx       2     )     ⁢   sin   ⁢           ⁢   2   ⁢   ϕ       ]       }     ·     cos   2       ⁢   β             Eqn   .           ⁢     (   1   )               
 
         [0024]     As further noted in  FIG. 3B , the NMR peak shape can include information about the local magnetic environment with one environment separating to one side of the spectrum versus the other environments. In addition, the peak separation between the two NMR peaks of  FIG. 3B  provides information about the thickness of the cylindrical shell of the film  20  (see  FIGS. 3C-3D ). In addition, the separation provides information about the angle between B 0  and the principal rotor axis  14  of the cylinder of the device  10  (see  FIGS. 3E-3F ).  
         [0025]      FIGS. 4A-4C  show the accompanying NMR spectra associated with the state of manufacture and an end product film  30 . In the state when the material is deposed on a cylinder  12  of the device  10 , but is not being spun, the static spectrum is an irregular, broad peak. After spinning at a preferred, “magic angle” (54.7°; v=2.9 kHz and T=341 K), the liquid film has a sharp NMR peak. After spinning is stopped, and the end product film  30  has solidified, the spectrum establishes a broad twin peak characteristic of a particular thickness and orientation of the final end product film  30 .  
         [0026]     Further, the device  10  of  FIG. 1  can be used to obtain films from compounds that are soft and waxy at room temperature. The existing device  10  enables stable spinning at frequencies between 1 and 4 kHz, during which compounds inside the spinning cylinder  12  are pushed by the gravitational force onto the walls of the cylinder  12 . The centrifugal force reshapes compounds into thin cylindrical shells, i.e., thin classic film product (see film  34  in  FIG. 4C ). When the device  10  is placed inside the NMR apparatus, the features of the thin classic film product  34  can easily be analyzed, while it is spinning at high and low speeds and upon shutting the spinning off. High resolution NMR spectra of the end product film  34  formed within the device  10  under conditions of magic angle spinning (MAS) do not provide orientational information of the component molecules, but these spectra are useful for compound identification, obtaining proper spin counts, and establishing whether there are impurities in the film product  34 . As the spinning of the cylinder  12  is turned off, the static spectra that provide molecular orientation information can be obtained. Slow spinning of the cylinder  12  is also useful for characterizing the thickness, shape, and orientation of the end film product  34 .  
         [0027]     In the context of a molecule nanoweaver methodology, the term “classic film” refers to a film in which molecules do not have preferential orientations; the component molecules that make up a film assume all possible orientations since they tumble isotropically at elevated temperatures before they are locked in random positions upon cooling. The lineshape in the static NMR spectrum of a classic film is due to the shape of the sample. Thus, by knowing only the geometrical shape of the sample container (e.g., the cylinder  12 ), a theoretical model can be used to predict the lineshape. In a theoretical model (see Eqn. 1), the lineshape due to the shape of the sample is scaled by the term that is related to the thickness of the end film product  34 . In order to compare the theoretical lineshape to the experimental results, the lineshape is also scaled by the magnetic susceptibility of the compound used in the experiment (see  FIGS. 2A-2C  and Eqn. 1).  
         [0028]     The theoretical model predicts that the static film product  34  obtained inside the cylinder  12 , has a characteristic lineshape that is a doublet whose center is at the isotropic value of the chemical shift for the specific compound. Theoretical lineshapes for nonadecane films shown in  FIG. 5A  have been scaled by the film thickness parameter and molecular parameters that relate to the magnetic susceptibility of nonadecane. To see if the theoretical lineshapes, based on the geometric factor, agree with experimental results, several nonadecane films of different thicknesses were prepared and studied. Theoretically predicted and experimentally obtained lineshapes for nonadecane films are shown in  FIGS. 5A and 5B , respectively. The substantial agreement between theory and experiment is clear, and this indicates that created end film products  34  are classic films. Yet, in  FIGS. 5A and 5B  the experimental and theoretical lineshapes for nonadecane films differ slightly in magnitudes of the splittings. The splitting is a distance (in ppm) between two peaks that make up a doublet. In calculations, values of film thickness are calculated from mass and density of the nonadecane placed inside the spinner, and the magnetic susceptibility parameter is experimentally determined. Since these scaling values have errors associated with them, the theoretical splittings are affected by these errors.  
         [0029]     Equations used in obtaining the theoretical lineshapes for nonadecane films of  FIG. 5A  are based on geometric shapes of thin films (see  FIG. 2A ). Yet, these equations can be modified to include molecular effects. Molecular information is contained in the components of the molecular shielding tensor. The shielding tensor components contribute to the peak lineshape in the situation when molecules have preferential orientations, which occur when molecules are ordered on the nanometer scale. We expect that as the process of building the molecule nanoweaver device  10  is completed and experiments are performed with the purpose of obtaining films with molecules ordered on the nanometer scale, then theoretical calculations will become crucial in the analysis of the experimentally obtained lineshapes. Such analysis can be performed using computer systems  53  (see  FIG. 8 ) with computer software modules to perform the appropriate mathematical analysis.  
         [0030]     In addition to high resolution spectra and static NMR spectra, unique information about prepared isotropic classic film product  34  can be deposited and processed by use of the toroid cavity detector (TCD) NMR spectrometer  40  (see  FIG. 8 ). The device  10  includes an outer housing  46 , a monomer source  47 , a bearing gas  48  for supporting the spinning cylinder  12 , and a drive gas  50  for pushing against drive fins  52  of the cylinder  12 . Also included is heating/cooling gas  54 , a vent  56  and a direct viewing device in the form of fiber optic cable  58  to view film formation and irradiate film with UV/VIS/IR light.  
         [0031]     The spinning cylinder  12  of the device  10  is, with the film product  34  cast on its inside walls inside the toroid cavity housing  46 , disposed so that the central axis conductor  42  of the cylinder  12  coincides with central conduit  44  that is connected to the TCD NMR spectrometer  40 . Ceramic capacitor  41 , variable capacitor  43 , central axis conductor  42 , and the housing  46  comprise a radiofrequency tunable resonant circuit useful for recording TCD NMR images. Resulting TCD NMR images are three-dimensional, with chemical shift, radial, and intensity dimensions (see, for example,  FIGS. 9A-9C  described below). Thus, the TCD NMR spectrometer  40  gives normal NMR spectra of compounds observed along the chemical shift axis. In addition, the radial information in the second dimension indicates how far away from the central axis conductor  42  the compound identified from the information along the chemical shift is located. The TCD NMR spectrometer  40  can thus be used to study multilayered classic films.  
         [0032]     In  FIGS. 6A-6E  is shown the characterization of a two-layer film composed of nonadecane (31.9 mg) and polyethylene glycol (PEG) (39.9 mg) which are introduced into the device  10  by the monomer source  47  or by alternate means. The resulting multilayer film  34  can be characterized by measurement of the NMR spectrum and comparing with the NMR spectrum of each constituent of the film  34 .  FIG. 6A  shows the recorded H-NMR spectrum of a two-layer film composed of an equal mole mixture of nonadecane (31.9 mg) and PEG (39.9 mg).  FIG. 6B  shows the recorded H-NMR spectrum of a film of nonadecane (31.9 mg).  FIG. 6C  shows the H-NMR spectrum of a film of PEG (39.9 mg). Various combined spectra are shown. The spectrum in  FIG. 6D  is the scaled sum, composed of a 1:1 ratio (also denoted 50:50), of the nonadecane spectrum of  FIG. 6B  and the PEG spectrum of  FIG. 6C . The spectrum in  FIG. 6E  is the scaled sum, composed of a 1:2.33 ratio (also denoted 30:70), of the nonadecane spectrum of  FIG. 6B  and the PEG spectrum of  FIG. 6C . If the measured H-NMR spectrum is not simply the sum of the two individual spectra, then some molecular change or component loss has occurred. In  FIGS. 7A-7E , experimental and simulation data for PEG-distearate illustrate further the deviation from identity and the substantial difference of the H-NMR spectrum when the cylinder  12  of the device  10  is spinning (see  FIG. 7B ) versus static (see  FIG. 7C ); the experimental static spectrum is compared to simulation results in  FIGS. 7D and 7E . The simulated static H-NMR spectrum shown in  FIG. 7D  was composed of a ratio, determined by the number of methylene protons in the alkane and polyethylene oxide (PEO) chains in the PEG-distearate molecule, of the nonadecane spectrum of  FIG. 6B  and the PEG spectrum of  FIG. 6C . The simulated static spectrum shown in  FIG. 7E  was composed of a ratio, determined by the number of methylene protons in the alkane and PEO chains in the PEG-distearate molecule, of two spectra of the form shown in  FIG. 2C  (displaced from each other by the chemical shift difference between the methylene protons in the alkane and PEO chains) calculated using Equation (1).  
         [0033]     One of the prepared films studied by TCD NMR spectrometer  40  contained polyethylene glycol (PEG) and polydimethyl siloxane (PDS). The TCD H-NMR image in  FIG. 9A  shows that PDS and PEG are macroscopically separated, since the peaks identifying each compound occur at different radial positions. In the prepared film  34  the outer layer is PEG, and the inner one is PDS. This separation of PEG from PDS was done by application of a centrifugal field force, and was due to the immiscibility and difference in density of the two compounds.  
         [0034]     In another illustration of the invention, three compounds (PEG, PDS, and nonadecane) were used to prepare the classic film  34 . The TCD H-NMR images of this system in  FIGS. 9B-9C  indicate that the resulting film  34  is composed of two layers, and further shows that the outside layer is PEG.  FIGS. 9B-9C  also show that the inside layer is a mixture of PDS and nonadecane. Thus, the TCD H-NMR results show that PDS and nonadecane are miscible with each other, but not with PEG. Units on the radial axis of  FIGS. 9A-9C  can be mathematically transformed in a known manner into real units of distance.  
         [0035]      FIGS. 10A-11  illustrate the dynamics of molecular assemblage and relaxation after spinning is stopped for the cylinder  12  of the device  10 . The NMR spectrum at the end of the spinning ( FIG. 10A ) differs more and more as time passes ( FIGS. 10B and 10C ), which illustrate the mobility and configurational changes of the molecules that compose the thin film  34 .  FIG. 11  shows a graph of the peak maximum signal intensity of a series of H-NMR spectra of a typical nonadecane or PEG film  34 , which includes data typified by the spectra shown in  FIGS. 10A-10C , versus time in minutes. The curve was fit by the bi-exponential function: y=y 0 +ae −bx +ce −dx . The parameters b and d describe two characteristic time constants that are associated with the dynamical processes of the molecules that compose the film  34 , and that collectively are termed rheology relaxation parameters. The parameter b characterizes the faster relaxing component of the curve and ranges between 1 and 10 minute depending on the film  34 , temperature and other factors; similarly, the parameter d characterizes the slower relaxing component of the curve and ranges between 50 minutes and 2 hours.  
         [0036]      FIG. 12  illustrates another application in the form of a multilayer capsule  70  which can be a time release geometry for pharmaceuticals. The different layer thicknesses can allow design of different time releases from very short to long duration. There can also be delay periods by having an inert layer disposed between active substance layers. Such a capsule geometry can readily be manufactured by the device  10  and designed and monitored by the methods of the invention described herein.  
         [0037]      FIG. 13  shows a series of NMR spectra of the cylindrical film  34  spinning at different speeds between 0 and approximately 1000 revolutions per second. The spinning axis, which is parallel to the central axis conductor  42 , and the direction of the NMR magnetic field form an angle of 54.7°. The patterns of peaks in each NMR spectrum provide information that characterizes the morphology and orientation of the film. The method of spinning the cylinder film  34  at various angles (also known as off-magic angle spinning, or variable angle spinning) provides details of the film&#39;s structure and dynamics.  
         [0038]     It should be understood that various changes and modifications referred to in the embodiment described herein would be apparent to those skilled in the art. Such changes and modifications can be made without departing from the spirit and scope of the present invention.