COLORIMETRIC PLASMONIC NANOSENSOR FOR DOSIMETRY OF THERAPEUTIC LEVELS OF IONIZING RADIATION

Abstract

An apparatus includes a solution including a metallic compound, a surfactant, and an acid. The solution is substantially colorless. A container holds the solution. A radiated solution is formed when the solution receives a low dose of ionizing radiation

Claims

1.-34. (canceled)

35. An apparatus comprising: a radiation source; an irradiated solution including a metallic compound, a C.sub.12TAB or C.sub.16TAB surfactant, and an acid, the irradiated solution irradiated by a low dose of ionizing radiation from the radiation source; and a container to hold the irradiated solution.

36. The apparatus of claim 35, wherein the irradiated solution has a color and the color has a color intensity that increases with an increase in the low dose of ionizing radiation.

37. The apparatus of claim 35, wherein the irradiated solution is formed from a solution having a substantially linear response to the low dose of ionizing radiation.

38. The apparatus of claim 35, wherein the low dose of ionizing radiation has a value of between about 0.5 Gy and about 2.0 Gy.

39. The apparatus of claim 35, wherein the low dose of ionizing radiation has a value of between about 1.7 Gy and about 2.2 Gy.

40. The apparatus of claim 35, wherein the low dose of ionizing radiation has a value of between about 3.0 Gy and about 10.0 Gy.

41. The apparatus of claim 35, wherein the irradiated solution includes a plasmonic nanoparticle.

42. The apparatus of claim 37, wherein the C.sub.12TAB or C.sub.16TAB surfactant has a concentration and the solution has a color response and modifying the concentration of the surfactant changes the color response of the solution in response to changes to the low dose of ionizing radiation.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0008] FIG. 1 shows a schematic (Adapted from Pérez-Juste, J.; Liz-Marzán, L. M.; Carnie, S.; Chan, D. Y. C.; Mulvaney, P., Electric-Field-Directed Growth of Gold Nanorods in Aqueous Surfactant Solutions. Advanced Functional Materials 2004, 14 (6), 571-579.) depicting the reaction progress after addition of various components in the plasmonic nanosensor for ionizing radiation.

[0009] FIGS. 2A-2C shows a UV-Vis absorption spectra of the control (0 Gy), irradiated samples containing (FIG. 2A) C.sub.16TAB, (FIG. 2B) C.sub.12TAB and (FIG. 2C) C.sub.8TAB after 7 hours.

[0010] FIGS. 3A-3E shows optical images of samples containing different C.sub.16TAB and C.sub.12TAB concentrations irradiated with a range of X-ray doses (Gy) (FIG. 3A) 2 mM C.sub.16TAB, (FIG. 3B) 4 mM C.sub.16TAB, (FIG. 3C) 10 mM C.sub.16TAB, (FIG. 3D) 20 mM C.sub.16TAB and (FIG. 3E) 20 mM C.sub.12TAB 2 hours post irradiation.

[0011] FIG. 4. Maximum absorbance vs. radiation dose for varying concentrations of C.sub.16TAB after 2 hours post irradiation. Red filled diamonds, solid line: 2 mM C.sub.16TAB, Orange filled circles, dashed line: 4 mM C.sub.16TAB, Green filled triangles, solid line: 10 mM C.sub.16TAB, and Blue filled squares, solid line: 20 mM C.sub.16TAB.

[0012] FIGS. 5A-5D shows Transmission Electron Microscopy (TEM) images of nanoparticles after exposure to ionizing (X-ray) radiation using two different lipid surfactants, 20 mM C.sub.16TAB (left) and 20 mM C.sub.12TAB (right). (FIG. 5A) 1 Gy, (FIG. 5B) 47 Gy, (FIG. 5C) 5 Gy and (FIG. 5D) 47 Gy.

[0013] FIGS. 6A-6B shows (FIG. 6A) An endorectal balloon with precursor solution before irradiation with X-rays and (FIG. 6B) Endorectal balloon post irradiation with 10.5 Gy X-rays.

[0014] FIGS. 7A-7B shows (FIG. 7A) Digital image showing the nanoscale precursor solution (200 μL) in microcentrifuge tubes placed along the stem outside of an endorectal balloon and (FIG. 7B) X-Ray contrast image of the phantom which shows the dose treatment plan, prostate tissue, the endorectal balloon, and the microcentrifuge tube/nanosensor location below the prostate tissue and on the endorectal balloon and (FIG. 7A)[[.]] Digital image of the plasmonic nanosensor 2 h following treatment with X-rays in the prostate phantom.

[0015] FIG. 8 shows an apparatus including a solution and a container.

[0016] FIG. 9 shows a method including mixing a metal compound with a surfactant to form a mixture and adding an acid to the mixture to form a substantially colorless solution.

[0017] FIG. 10 shows a method including mixing a fixed concentration of HAuCl.sub.4 with a known concentration of surfactant to form a mixture and adding ascorbic acid in varying concentrations to the mixture to form a substantially colorless solution.

[0018] FIG. 11 shows a method including receiving a dose of ionizing radiation having a low ionizing dose value at a solution to form an irradiated solution including metallic nanoparticles and having an irradiated solution color and identifying the ionizing dose value by analyzing the irradiated solution color.

[0019] FIG. 12 shows a method including receiving a dose of ionizing radiation having a low ionizing dose value at a solution to form an irradiated solution including metallic nanoparticles and having an irradiated solution color and identifying the ionizing dose value by observing the irradiated solution color with a human visual system.

[0020] FIG. 13 shows a method including receiving a low dose of ionizing radiation to induce a color change in a solution including a surfactant, a metal, and an acid and observing the color change.

[0021] FIG. 14 shows a method including receiving a low ionizing radiation dose at a substantially colorless salt solution including univalent gold ions (Aul) and templating lipid micelles to form substantially maroon-colored dispersions of plasmonic gold nanoparticles.

[0022] FIG. 15 shows a method including receiving a low dose of ionizing radiation at a solution including metal salts and templating lipid micelles to form colored dispersions from nanoparticle formations in the solution.

[0023] FIG. 16 shows a method including receiving a low dose of ionizing radiation at a solution including metal salts and templating lipid micelles to form metal nanoparticles from the metal salts.

[0024] FIG. 17 shows a method that includes delivering a therapeutic dose of radiation to an animal and a dosimeter and measuring the therapeutic dose of radiation at the dosimeter, the dosimeter including a solution having metallic nanoparticles after receiving the therapeutic dose of radiation.

[0025] FIG. 18 shows a method that includes delivering a therapeutic radiation dose having a radiation value to a human and a solution including a surfactant, a metal, and an acid to form a radiated solution having a color and determining the radiation value by analyzing the color.

[0026] FIG. 19 shows UV-Visible spectral profiles of (A) HAuCl.sub.4, (B) HAuCl.sub.4 (0.196 mM)+C.sub.16TAB (20mM), (C) HAuCl.sub.4 (0.196 mM)+C.sub.16TAB (20 mM)+Ascorbic Acid (5.88 mM) and (D) HAuCl.sub.4 (0.196 mM)+Ascorbic Acid (5.[[88 mM)AA).

[0027] FIGS. 20A-20B shows (FIG. 20A) UV-Vis spectra of varying ascorbic acid volumes along with gold and C.sub.16TAB irradiated at 47 Gy and (FIG. 20B) maximum absorbance values of samples containing varying concentrations of ascorbic acid denoted as [AA].

[0028] FIGS. 21A-21C shows absorbance spectra of (FIG. 21A) gold salt (0.196 mM) (FIG. 21B) gold salt (0.196 mM)+C.sub.16TAB (20 mM) (FIG. 21C) gold salt (0.196 mM)+C.sub.12TAB (20 mM).

[0029] FIGS. 22A-22C shows kinetics of gold nanoparticle formation following exposure to different doses of ionizing radiation (0-47 Gy) for (FIG. 22A) C.sub.16TAB, (FIG. 22B) C.sub.12TAB and (FIG. 22C) C.sub.8TAB.

[0030] FIG. 23 shows maximum absorbance vs. radiation dose (Gy) after 2 hours of X-ray irradiation. C.sub.16TAB (red filled squares, solid line) and C.sub.12TAB (orange open circles, dotted line) surfactants.

[0031] FIG. 24 shows intensity ratio of 1337/1334 as a function of surfactant concentration is used to determine the critical micellar concentration.

[0032] FIGS. 25A-25C shows absorbance spectra of precursor monovalent gold salt solutions under conditions of no radiation (i.e. 0 Gy) in presence of different concentrations of (FIG. 25A) C.sub.16TAB and (FIG. 25B) C.sub.12TAB (FIG. 25C) C.sub.8TAB recorded after 10 minutes of incubation.

[0033] FIGS. 26A-26D shows Maximum Absorbance vs. Wavelength for different concentrations of C.sub.16TAB after a duration of 2 hours post irradiation (FIG. 26A) 2 mM (FIG. 26B) 4 mM (FIG. 26C) 10 mM (FIG. 26D) 20 mM.

[0034] FIGS. 27A-27B shows (FIG. 27A) Hydrodynamic diameter vs. radiation dose and (FIG. 27B) Hydrodynamic diameter vs. radiation dose on a log.sub.10 scale.

[0035] FIGS. 28A-28D shows transmission electron microscopy (TEM) images of anisotropic nanostructures (FIG. 28A) dendritic and (FIG. 28C) nanowire-like structures formed in case of C.sub.12TAB at 5 Gy X-ray radiation dose and images (FIG. 28B) and (FIG. 28D) show magnified images of the highlighted regions inside red box from Figures (FIG. 28A) and (FIG. 28C).

[0036] FIGS. 29A-29G shows Transmission Electron Microscopy (TEM) images of nanoparticles formed after exposure to ionizing (X-ray) radiation using the following conditions of C.sub.16TAB: (FIG. 29A) 10 mM and 5 Gy, (FIG. 29B) 10 mM and 47 Gy, (FIG. 29C) 4mM and 5 Gy, (FIG. 29D) 4 mM and 15 Gy, (FIG. 29E) 2 mM and 0.5 Gy, (FIG. 29F) Magnified image of highlighted area of E, and (FIG. 29G) 2 mM and 2.5 Gy.

[0037] FIG. 30 shows a digital image showing the phantom irradiation set up on the linear accelerator at Banner MD Anderson.

DESCRIPTION

[0038] Facile radiation sensors have the potential to transform methods and planning in clinical radiotherapy. Below are described results of studies on a colorimetric, liquid-phase nanosensor that can detect therapeutic levels of ionizing radiation. X-rays, in concert with templating lipid micelles, were employed to induce the formation of colored dispersions of gold nanoparticles from corresponding metal salts, resulting in a easy to use visible indicator of ionizing radiation.

[0039] The novel plasmonic nanosensor employs a colorless metal salt solution comprising a mixture of auric chloride (HAuCl.sub.4), L-Ascorbic acid (AA) and cetyl (C.sub.16), dodecyl (C.sub.12), or octyl (C.sub.8) trimethylammonium bromide (C.sub.x; x=16/12/8TAB) surfactant molecules (FIG. 1; please see the Experimental Section for more details). In brief, C.sub.xTAB and HAuCl.sub.4 were first mixed leading to the formation of Au.sup.IIIBr.sub.4.sup.−. HAuCl.sub.4 shows a prominent peak at 340 nm which shifts to 400 nm after addition of C.sub.16TAB, likely due to the exchange of a weaker chloride ion by a stronger bromide ion (FIGS. 19A and 19B, Supporting Information section). The shift in absorption peak can also be seen visually as a color change from yellow to orange. Subsequent addition of ascorbic acid turns the solution colorless with no observable peaks between 300 and 999 nm (FIG. 19C, Supporting Information section). Ascorbic acid reduces Au(III) to Au(I) in a two-electron, step-reduction reaction. It has been shown that addition of up to 5 molar equivalent excess ascorbic acid does not result in the formation of zerovalent gold or Au(0) species, which can be partly attributed to the lower oxidation potential of the acid in presence of C.sub.16TAB. This mixture of C.sub.xTAB, ascorbic acid, and HAuCl.sub.4 is employed as the precursor solution for radiation sensing. However, a characteristic peak in the range of 500-600 nm corresponding to gold nanoparticles is observed if ascorbic acid directly reacts with the gold salt in the absence of C.sub.16TAB (FIG. 19D, Supporting Information section), indicating spontaneous formation of nanoparticles in absence of the surfactant under the conditions employed.

[0040] First, attempts were made to convert trivalent gold to its univalent state, since the reduction of Au(I) to Au(0) is thermodynamically favored over the reduction of Au(III) to Au(0), due to a higher standard reduction potential of the former. Au(I) has an electronic configuration of 4f.sup.145d.sup.10, and requires a single electron for conversion (reduction) to Au(0). This formation of zerovalent gold or Au(0) is a prerequisite step for nanoparticle formation. In the current plasmonic nanosensor, the electron transfer required for converting Au(I) to Au(0) is facilitated by splitting water into free radicals following exposure to ionizing radiation (X-rays).

[0041] Water splitting by ionizing radiation generates three key free radicals, two of which, e.sup.− and H., are reducing, and the other (.OH.) oxidizing in nature. Excess ascorbic acid is an antioxidant capable of removing the detrimental (oxidizing) OH. radicals generated in the system. C.sub.xTAB surfactants were employed due for their ability to template gold nanoparticles. These three species, namely ascorbic acid, C.sub.xTAB, and gold salt, form the key constituents of the current plasmonic nanosensor for ionizing radiation.

[0042] First, the concentration of ascorbic acid (AA) was optimized in the presence of the surfactant (C.sub.16TAB) and gold salt employed in the plasmonic nanosensor; the maximal dose of 47 Gy was delivered in order to study the effect of ascorbic acid on nanoparticle formation (FIGS. 20A-20B, Supporting Information section). A marked increase in nanoparticle formation is observed when excess AA is used and it reaches saturation when 600 μL of 0.01 M (4 mM AA) is employed; similar levels of nanoparticle formation are seen when 900 μL of 0.01 M (5.88 mM AA) are employed. Although saturation was observed when 600 μL of AA were used, 5.88 mM AA was used for all subsequent experiments in order to ensure adequate quenching of the detrimental OH. radicals which otherwise adversely affects the yield of nanoparticles generated. Control experiments with (1) gold salt (HAuCl.sub.4) alone, (2) gold salt+C.sub.16TAB and (3) gold salt+C.sub.12TAB were also carried out in presence of different X-ray doses, but in absence of ascorbic acid. Absorbance profiles of the samples were measured after 7 hours and the absence of peaks from 500-900 nm indicated the absence of plasmonic (gold) nanoparticles (FIGS. 21A-21C, Supporting Information section).

[0043] Next, the efficacy of three cationic surfactants, C.sub.8TAB C.sub.12TAB, and C.sub.16TAB was investigated, for inducing nanoparticle formation in presence of different doses of ionizing radiation (FIGS. 2A-2C). All three surfactants have trimethyl ammonium moieties as the head group and bromide as the counter ions; only the lipid chain length was varied as C.sub.8, C.sub.12, and C.sub.16 in these molecules. As stated previously, a large number of e.sup.−.sub.aq and H. radicals are generated following exposure of the solution to X-rays which facilitate the conversion of Au.sup.+ ions to their zerovalent Au.sup.0 state. The Au.sup.0 species act as seeds upon which further nucleation and coalescence occurs. This, in turn, leads to an increase in size and eventual formation of nanoparticles, which are stabilized by surfactant molecules. Formation of these plasmonic nanoparticles imparts a burgundy/maroon color to the dispersion; the intensity of the color increases with an increase in radiation dose applied (FIGS. 3A-3E).

[0044] Nanoparticle formation was seen as early as 1 h following irradiation in many cases, although 2 h were required for samples irradiated with lower doses (1, 3 and 5 Gy) (FIGS. 22A-22C, Supporting Information section). No significant differences in absorbance intensity were observed thereafter until a period of 7 hours, which was the maximum duration investigated in these cases. Nanoparticle formation was observed at radiation doses as low as 1 Gy, which is well within the range of doses employed for radiotherapy. While C.sub.16TAB or C.sub.12TAB were effective at templating nanoparticle formation even at low doses (1-5 Gy), C.sub.8TAB did not show any propensity for templating nanoparticle formation even at the highest radiation dose (47 Gy) employed. C.sub.12TAB-templated gold nanoparticles exhibited unique spectral profiles under ionizing radiation; two spectral peaks—one between 500 and 550 nm and another between 650 and 800 nm—were seen (FIG. 2B). This is in contrast to C.sub.16TAB which exhibited only a single peak between 500 and 600 nm (FIG. 2C). Finally, the linear response for C.sub.16TAB was significantly more pronounced than that for C.sub.12TAB (FIG. 23).

[0045] The critical micelle concentration (CMC) of C.sub.16TAB is reported to be approximately 1 mM. Using the pyrene fluorescence assay, we determined the CMC of C.sub.16TAB in the nanosensor precursor solution (i.e. gold salt and ascorbic acid in water) to be ˜0.7±0.1 mM, which is slightly lower than ˜1.2±0.02 mM in THIS solvent (FIG. 24, Supporting Information section). Pre-micellar aggregates are thought to exist when C.sub.16TAB concentration is lower than 7.4 mM, while stable micelles are observed at higher concentrations of the lipid surfactant. One hypothesis is that increasing the ratio of the metallic species (Au.sup.+) to the aggregate (pre-micellar/micellar) C.sub.16TAB species would lead to greater propensity for nanoparticle formation upon exposure to ionizing radiation and therefore increased sensitivity of the resulting nanosensor at lower radiation doses. Based on the hypothesis that the number of aggregate species increases with lipid concentration, lower concentrations of C.sub.16TAB (2 mM, 4 mM and 10 mM) was investigated, while keeping the gold and ascorbic acid concentration constant.

[0046] Use of C.sub.16TAB concentrations at and below the CMC (i.e. 0.7 and 0.2 mM) resulted in spontaneous formation of gold nanoparticles in absence of ionizing radiation; gold nanoparticle formation can be seen by the characteristic absorbance peak of the dispersion in FIGS. 25A-25C, Supporting Information Section. However, the propensity for spontaneous nanoparticle is significantly reduced or lost at concentrations above the CMC. A distinct color change can be observed for radiation doses as low as 0.5 Gy for the lowest concentration of C.sub.16TAB above the CMC investigated (FIGS. 3A and 26A-26D, Supporting Information section). A linear response was observed for radiation doses ranging from 0.5 to 2 Gy under these conditions (FIGS. 5A-5D). As the concentration of C.sub.16TAB increases, the radiation dose required to template nanoparticle formation also increases (FIGS. 4 and 26A-26D, Supporting Information section). Furthermore, the color of the nanoparticle dispersion formed is significantly different in cases of 2 mM (blue-violet) C.sub.16TAB compared to that observed in cases of 4 mM (bluish-red), 10 mM (red/pink) and 20 mM (burgundy/maroon) C.sub.16TAB, indicating different sizes of nanoparticles under these conditions. While it is most desired that the nanosensor is sensitive to therapeutic doses used in conventional and hyperfractionated radiotherapy (˜0.5-2.2 Gy), these results indicate that the response of the plasmonic nanosensor can be tuned by simply modifying the concentration of the lipid surfactant.

[0047] Visual colorimetric sensors possess advantages of convenience and likely, cost, over those that employ fluorescence changes or electron spin resonance measurements for detecting ionizing radiation. The current plasmonic nanosensor shows increasing color intensity with increasing radiation dose (FIGS. 2A-2C and 3A-3E). The increase in color intensity with radiation dose is reflected in an increase in maximal (peak) absorbance values, which in turn, are surrogates for the concentrations of nanoparticles formed in the dispersion. Key features of gold nanoparticle absorbance spectra include the shape of the surface plasmon resonance band and the position of the maximal (peak) absorption wavelength. The width of the spectral profiles at lower doses signifies a somewhat polydisperse population of the nanoparticles (FIGS. 2A-3C and FIGS. 26A-26D Supporting Information section). The absorbance peaks are red-shifted with decreasing radiation doses, suggesting an increase in particle size under these conditions compared to those obtained at higher doses.

[0048] Free radicals generated upon radiolysis are thought to be localized in finite volumes called spurs. These spurs can expand, diffuse, and simultaneously, react, leading to the formation of molecular products. These highly reactive free radicals have very short lifetimes of ˜10.sup.−7-10.sup.−6 s at 25° C. Reaction volumes consisting of nanoscale features can facilitate enhanced reaction kinetics and ensure efficient utilization of these free radicals for the formation of nanoparticles. In case of the current plasmonic nanosensor, this was achieved by the use of amphiphilic molecules that self-assemble into micelles above their respective critical micellar concentrations (CMCs). A strong interaction is possible between the positively charged head group of the lipid surfactant micelles and the negatively charged AuCl.sub.4.sup.− ions (FIG. 1). This interaction can lead to incorporation of AuCl.sub.4.sup.− ions in the water-rich Stern layer leading to the formation of a ‘nanoreactor’. However, spontaneous formation of nanoparticles (i.e. in absence of ionizing radiation) was seen when concentrations of C.sub.16TAB were lower than the CMC (FIGS. 25A-25C Supporting Information section). One hypothesis is that spontaneous nanoparticle formation observed at lower concentrations of the surfactant is likely due to negligible steric hindrance between the surfactant and ascorbic acid; absence of these barriers results in nanoparticle growth which can be spectroscopically observed. It is only when the concentrations of C.sub.12TAB and C.sub.16TAB are higher than the CMC, that no spontaneous formation of gold nanoparticles is seen, and ionizing radiation is required to induce nanoparticle formation. This, therefore, acts as the functional principle behind the current plasmonic nanosensor. Of the three lipid surfactants, only the concentration of C.sub.8TAB was significantly below its CMC value (130 mM), while the concentrations employed were significantly higher than the CMCs of C.sub.12TAB (CMC=15 mM) and C.sub.16TAB (CMC=1 mM). In the case of C.sub.8TAB, there is an absence of these “nanoreactors”, which may explain lack of nanoparticle formation under these conditions. These observations suggest that interplay between surfactant chemistry and aggregation state determine nanoparticle formation by lipid-based surfactant molecules.

[0049] Nanoparticles formed in presence and absence of ionizing radiation were characterized for their morphology and hydrodynamic diameter using transmission electron microscopy (TEM; FIGS. 5A-5D, and FIGS. 28A-28D and 29A-29G, Supporting Information section) and dynamic light scattering (FIGS. 27A-27B, Supporting Information section), respectively. While C.sub.16TAB-templated nanoparticles showed a single maximal absorption peak (at ca. 520 nm), C.sub.12TAB-templated nanoparticles showed two peaks: one at ca. 520 nm (visual region) and another at ca. 700 nm (near infrared or NIR region; FIG. 2B), particularly at higher doses of ionizing radiation. TEM images indicated that a mixture of spherical and rod-shaped nanoparticles was observed at the higher radiation doses (47 Gy) in case of C.sub.12TAB as the templating surfactant (FIG. 5D). This explains the absorption spectral profile with peaks in both, the visual and near infrared range of the spectrum in case of nanoparticles templated using C.sub.12TAB (FIG. 2B). A significant decrease in the near infrared absorption peak is observed at lower X-ray doses. Although the spectral profile indicates formation of gold nanospheres, we observed an ensemble of unique anisotropic (dendritic and nanowire) structures (FIGS. 28A-28D, Supporting Information section). Such structures were not observed at similar X-ray doses in case of C.sub.16TAB as the templating surfactant.

[0050] The growth of gold nuclei from zerovalent gold species proceeds through continuous diffusion of unreacted metal ions and smaller seeds onto the growing nanocrystal surface. This, in turn, is governed by electrostatic interactions between the cationic micelle loaded with gold seeds and unreacted metal ions. In this case, it is likely that the gold nanoparticles aggregate more rapidly in situ due to the strong hydrophobic nature of the long of C.sub.16TAB chains, leading to the formation of quasi-spherical nanoparticles and not anisotropic nanostructures.

[0051] TEM images indicated a reduction in the size of the metal nanoparticles with increasing radiation dose. Dynamic light scattering (DLS) studies on irradiated samples (FIGS. 27A-27B, Supporting Information section and Table 3, Supporting Information section) indicated a linear decrease in nanoparticle hydrodynamic diameters with increases in X-ray dose, which is in good agreement with information from TEM images. High radiation doses generate a larger number of free radicals in comparison to lower radiation doses, which can lead to the reaction with and therefore, consumption of a higher number of metal ions. This leads to the formation of a higher concentration of zerovalent gold species in comparison to samples irradiated at lower doses. These unstable Au(0) seeds grow and are eventually capped by the cationic surfactant resulting in smaller sized nanoparticles. In contrast, at lower doses of ionizing radiation, the ratio of concentration of Au(0) to Au(I) is likely smaller. It is possible that unreacted metal ions coalesce with the smaller population of gold seeds and in turn lead to the formation of nanoparticles with larger diameters.

[0052] The translational potential of a plasmonic nanosensor for detecting X-ray radiation was investigated under conditions that simulate those employed in human prostate radiotherapy. Endorectal balloons are typically used for holding the prostate in place and for protecting the rectal wall during radiotherapy treatments in humans. The efficacy of the plasmonic nanosensor was evaluated in these balloons ex vivo; no studies on human patients were carried out. 1.5 ml of the precursor solution (C.sub.16TAB (20mM)+AA+HAuCl.sub.4) was incorporated into endorectal balloons as shown in FIG. 6A. The nanosensor precursor solution was subjected to two clinically relevant doses of 7.9 and 10.5 Gy (n=3). The absorbance of the plasmonic nanosensor, which changes color in the balloon itself (e.g. light pink color seen in FIG. 6B for a balloon subjected to a radiation dose of 10.5 Gy) was employed to determine the radiation dose delivered to the balloon. A calibration curve between 5 and 37 Gy from the plot between maximum absorbance and radiation dose after 7 hours was employed to determine the radiation dose delivered. Doses of 8.51±1.73 Gy and 7.85±2.05 Gy were calculated from the calibration curve for 10.5 Gy and 7.9 Gy respectively. Due to the nonlinearity of the curve below 5.3 Gy, the control (0 Gy) showed a value 4.38±0.41 Gy (n=3) when the calibration equation was employed, indicating that the operating region of the plasmonic nanosensor, with a CTAB concentration of 20 mM, is between 5 and 37 Gy and is not reliable for lower doses of radiation for CTAB concentrations of 20 mM (Table 1).

[0053] Based on the above findings in the endorectal balloon, the detection efficacy of the plasmonic nanosensor in a phantom that is employed to simulate prostate radiotherapy treatments was investigated. In these studies, 200 μL of the precursor solution (C.sub.16TAB (2 mM)+AA+HAuCl.sub.4) was filled in microcentrifuge tubes, which were then taped to the outside surface of an endorectal balloon such that they were aligned along the stem (FIG. 7A). The lower concentration of C.sub.16TAB was used, since this concentration results in detection between 0.5-2 Gy (FIGS. 3A-3E top panel). The prostate phantom, with the endorectal balloon placed under the simulated prostate tissue, was irradiated based on a treatment plan described in the Experimental section and shown in FIGS. 30 and 7B. The prostate itself was irradiated with 1 Gy, while the dose fall off at the end was 0.5 Gy (n=3; FIG. 7B). Thus, two microcentrifuge tubes (capsules 1 and 2) along the stem of the balloon just below the prostate were subjected to 1 Gy, while the third one (capsule 3) outside the balloon was subjected to 0.5 Gy. This set up was employed in order to obtain spatial information on the delivered dose along the rectal wall in the tissue phantom.

[0054] Optical images (FIG. 7A) clearly indicate the formation of violet colored dispersions for capsules 1 and 2, while a dispersion of lighter intensity can be seen in capsule 3. The absorbance of the dispersions were measured 2 h following exposure to radiation, and a calibration curve was employed to estimate the radiation dose as indicated by the radiation sensor. Table 2 shows a comparison of the actual dose delivered and the dose estimated from the calibration of the plasmonic nanosensor. The plasmonic nanosensor indicates that capsules 1 and 2 received doses of 1.20±0.11 Gy and 1.17±0.16 Gy, respectively, while capsule 3 received a dose of 0.49±0.04 Gy (Table 2). These are highly reasonable estimates of the actual doses received by the capsules in the tissue phantom, and can be employed to obtain spatial information on the radiation dose delivered. Taken together, the results indicate the utility of the plasmonic nanosensor in as a simple detection system in simulated clinical settings.

[0055] The application discloses an easy to use, versatile and powerful nanoscale platform for dosimetry of therapeutically relevant doses of radiation. This method involves readily available chemicals, is easy to visualize due to the colorimetric nature of detection, and does not need expensive equipment for detection. While a ‘yes/no’ determination may be made by the naked eye, only an absorbance spectrophotometer is required for quantifying the radiation dose. A visible color change also ensures the ease of detecting the radiation dose with the naked eye. It was found that both, C.sub.12TAB and C.sub.16TAB were able to function as templating molecules in the plasmonic nanosensor at concentrations above their critical micelle concentration (CMC). The sensitivity of the sensor to lower radiation doses is enhanced by modifying the concentration of C.sub.16TAB, thus making this a highly versatile platform for a variety of applications. Apart from the surfactants used a list of other potential surfactants which could be employed are listed in the Table 4. The chemicals included in the list along with their derivatives are potential chemicals which could be used along with our sensor in its current form or in any other formulation. The metal ions used is not limited to gold. Any species either metallic or non-metallic can be used along with the sensor in its current form or in any other formulation. To name a few, ions of cobalt, iron, silver could be potential replacement for the proof of concept gold employed .The utility of the plasmonic nanosensor was demonstrated in translational applications; the plasmonic nanosensor was able to detect the delivered radiation dose with satisfactory accuracy when placed in an endorectal balloon ex vivo. In addition, the nanosenor was able to detect doses as low as 0.5 Gy and was able to report on the spatial distribution of radiation dose delivered when investigated using an endorectal balloon placed in a prostate tissue phantom. The translational application of such a dosimeter can help therapists with treatment planning and potentially enhance selectivity and efficacy of treatment. Apart from the medical field, this sensor could be employed where there is a need to detect ionizing radiation directly or indirectly.

Apparatus

[0056] FIG. 8 shows an apparatus 801 including a solution 803 and a container 805. A solution is a substantially homogeneous mixture of two or more substances, which may be solids, liquids, gases, or a combination of solids, liquids or gases. The solution 803 includes a metallic compound 807, a surfactant 809, and an acid 811. A metallic compound is compound that contains one or more metal elements. An exemplary metallic compound suitable for use in connection with apparatus 801 includes auric chloride (HAuCl.sub.4). A surfactant is a compound that lowers the surface tension (or interfacial tension) between two liquids. Exemplary surfactants suitable for use in connection with the apparatus 801 include cetyl trimethylammonium bromide (C.sub.16TAB) and dodecyl trimethylammonium bromide (C.sub.12TAB). In some embodiments, the apparatus 801 includes a surfactant 809 that has a critical micelle concentration of about 0.7+0.1 nm. The critical micelle concentration (CMC) is defined as the concentration of surfactants above which micelles form and all additional surfactants added to the system go to micelles. An acid is a chemical substance whose aqueous solutions are characterized by an ability to react with bases and certain metals to form salts. An exemplary acid 811 suitable for use in connection with the apparatus 801 includes L-ascorbic acid.

[0057] The container 805 holds the solution 803. Containers 805 suitable for use in connection with the apparatus 801 are not limited to particular types of containers. In some embodiments, the container 805 includes an endorectal balloon.

[0058] In operation, the solution 803 of the apparatus 801 receives a low dose of ionizing radiation 813 to form a radiated solution 815. In some embodiments, the irradiated solution 815 includes a plasmonic nanoparticle 816. A plasmonic nanoparticle is a particle whose electron density can couple with electromagnetic radiation having wavelengths that are larger than the particle due to the nature of the dielectric-metal interface between the medium and the particles.

[0059] In some embodiments, the low dose of ionizing radiation 813 is not limited to a particular radiation value. In some embodiments, the low dose of ionizing radiation 813 includes a therapeutic range of values such as between about 0.5 Gy and about 2.0 Gy. In some embodiments, the low dose of ionizing radiation 813 includes a range of values of between about 1.7 Gy and about 2.2 Gy. In some embodiments, the low dose of ionizing radiation 813 includes a value of between about 3.0 Gy and about 10.0 Gy

[0060] In some embodiments the solution 803 has a substantially linear response to the low dose of ionizing radiation 813. For a substantially linear response, the intensity of the color of the solution 817 increases substantially linearly as the low dose of ionizing radiation 813 increases.

[0061] The apparatus 801 may further include a detector 819 to analyze the radiated solution 815. In some embodiments, the detector 819 comprises a spectrophotometer. A spectrophotometer is an instrument for measuring electromagnetic radiation in different areas of the electromagnetic spectrum. In some embodiments, the detector 819 includes a human visual system. A human visual system is suitable for use in a variety of color measurement tasks and in particular for identifying changes in color. In some embodiments, the radiated solution 815 has a color and the color has a color intensity that increases with an increase in the low dose of ionizing radiation 813. In come embodiments, the surfactant 809 has a concentration and the solution 803 has a color response and modifying the concentration of the surfactant 809 changes the color response of the solution 803 to the low dose of ionizing radiation 813.

Composition of Matter

[0062] The solution 803 shown in FIG. 8 is a composition of matter. In some embodiments, the solution 803 includes the metallic compound 807, the surfactant 809, and the acid 811. An exemplary metallic compound includes auric chloride (HAuCl.sub.4). An exemplary surfactant includes cetyl trimethylammonium bromide (C.sub.16TAB). An exemplary acid suitable for use in forming the solution 803 includes L-ascorbic acid. In some embodiments, the solution 803 is substantially colorless.

Method of Making the Solution

[0063] Several methods may be employed to make the solution 803 shown in FIG. 8. FIG. 9 shows a method 901 including mixing a metal compound with a surfactant to form a mixture (block 903) and adding an acid to the mixture to form a substantially colorless solution (block 905). In some embodiments, mixing a metal compound with a surfactant to form a mixture includes mixing auric chloride (HAuCl4) with the surfactant to form the mixture. In some embodiments, adding an acid to the mixture to form a substantially colorless solution includes adding L-ascorbic acid to the mixture to form the substantially colorless solution.

[0064] FIG. 10 shows a method 1001 including mixing a fixed concentration of HAuCl.sub.4 with a known concentration of surfactant to form a mixture (block 1003) and adding ascorbic acid in varying concentrations to the mixture to form a substantially colorless solution (block 1005).

Methods

[0065] The apparatus 801 may be employed in a variety of methods useful in detecting radiation.

[0066] FIG. 11 shows a method 1101 including receiving a dose of ionizing radiation having a low ionizing dose value at a solution to form an irradiated solution including metallic nanoparticles and having an irradiated solution color (block 1103) and identifying the ionizing dose value by analyzing the irradiated solution color (block 1105).

[0067] FIG. 12 shows a method 1201 including receiving a dose of ionizing radiation having a low ionizing dose value at a solution to form an irradiated solution including metallic nanoparticles and having an irradiated solution color (block 1203) and identifying the ionizing dose value by observing the irradiated solution color with a human visual system (block 1205).

[0068] FIG. 13 shows a method 1301 including receiving a low dose of ionizing radiation to induce a color change in a solution including a surfactant, a metal, and an acid (block 1303) and observing the color change (block 13053). In some embodiments, observing the color change comprises observing the color change using a human visual system. In some embodiments, observing the color change includes observing the color change using a spectrophotometer.

[0069] FIG. 14 shows a method 1401 including receiving a low ionizing radiation dose at a substantially colorless salt solution including univalent gold ions (Aul) and templating lipid micelles to form substantially maroon-colored dispersions of plasmonic gold nanoparticles (block 1403).

[0070] FIG. 15 shows a method 1501 including receiving a low dose of ionizing radiation at a solution including metal salts and templating lipid micelles to form colored dispersions from nanoparticle formations in the solution (block 1503).

[0071] FIG. 16 shows a method 1601 including receiving a low dose of ionizing radiation at a solution including metal salts and templating lipid micelles to form metal nanoparticles from the metal salts (block 1603).

Therapeutic Methods

[0072] The apparatus 801 shown in FIG. 8 can be employed in a variety of therapeutic methods. For example, FIG. 17 shows a method 1701 that includes delivering a therapeutic dose of radiation to an animal and a dosimeter (block 1703) and measuring the therapeutic dose of radiation at the dosimeter, the dosimeter including a solution having metallic nanoparticles after receiving the therapeutic dose of radiation (block 1705). In another example, FIG. 18 shows a method 1801 that includes delivering a therapeutic radiation dose having a radiation value to a human and a solution including a surfactant, a metal, and an acid to form a radiated solution having a color (block 1803) and determining the radiation value by analyzing the color (block 1805).

EXPERIMENTAL

[0073] Materials: Gold(III) chloride trihydrate (HAuCl.sub.4.3H.sub.2O), trimethyloctylammonium bromide (C.sub.8TAB) (>98%), dodecyltrimethylammonium bromide (C.sub.12TAB) (≥98%) and L-Ascorbic acid (AA) were purchased from Sigma-Aldrich. Cetyl trimethylammonium bromide (C.sub.16TAB) was purchased from MP chemicals. All chemicals were used as received from the manufacturer without any additional purification.

[0074] Sample preparation for irradiation: First, 30 μL of 0.01 M HAuCl.sub.4 were mixed with 600 μL of 0.05 M C.sub.x=8,12,16TAB. Upon addition of 30 μL (0.196 mM), 300 μL (1.96 mM), 600 μL (3.92 mM approximated as 4 mM) and 900 μL (5.88 mM) of 0.01 M L-Ascorbic acid, the solution turned colorless after shaking; the concentrations of ascorbic acid were thus varied in order to examine its effect on nanoparticle formation (FIGS. 20A-20B, Supporting Information section). Unless specifically mentioned, the volume of AA used is 900 μL. The measured pH of the solution was between 2.9 and 3.1. Samples were prepared at Banner-MD Anderson Cancer Center, Gilbert, Ariz. prior to radiation.

[0075] Radiation Conditions: A TrueBeam linear accelerator was used to irradiate the samples. Samples were radiated at a dose rate of (15.6 Gy/min). The samples containing surfactant at a concentration of 20 mM and 10 mM were radiated at doses of 0 (Control), 1.1, 3.2, 5.3, 10.5, 15.8, 26.3, 36.9 and 47.4 Gy. These are reported as 0, 1, 3, 5, 10, 16, 26, 37 and 47 Gy respectively in the article. The samples containing surfactant at a concentration 2 mM and 4 mM were irradiated with 0 (Control), 0.5, 1, 1.5, 2, 2.5, 3, 5, 7.5, 10, 12.5 and 15 Gy. After irradiation the samples were transported back to Arizona State University in Tempe, Ariz. (one-way travel time of approximately 30 minutes).

[0076] Absorbance Spectroscopy: Absorbance profiles of the radiated and the control samples were measured using a BioTek Synergy 2 plate reader. Absorbance values from 150 μL of sample were measured from 300 to 900 nm with a step size of 10 nm in a 96 well plate. Nanopure water (18.2 MΩcm) was used as a blank in all cases. The absorbance was corrected for offset by subtracting A.sub.900 nm and the presence of a peak between 500 and 700 nm was used as an indicator for gold nanoparticle formation.

[0077] Determination of Critical Micellar Concentration (CMC): Pyrene (60 μL of 2×10.sup.−5M) in acetone was added to 20 ml glass vials. Upon acetone evaporation, 2 ml of C.sub.16TAB of varying concentrations was added and stirred for 6 hours at room temperature. To achieve the similar conditions as the irradiation experiments, 30 μL of 10 mM gold salt+600 μL of the above prepared C.sub.16TAB+900 μL of 10 mM ascorbic acid were mixed. A fluorescence spectrophotometer with an excitation scan range of 300-360 nm and an emission wavelength of 390 nm was used. Ratio of I.sub.337/I.sub.334 determined as a function of the surfactant concentration was used to calculate the CMC using pyrene as the probe based on methods described in the literature.

[0078] Dynamic Light Scattering (DLS) Measurements: 50 μL of the sample was transferred into a cuvette and placed into a Zetasizer Nano instrument. The software was set up to carry out measurements with autocorrelation. Thereafter, the average diameter along with the polydispersity index (PDI) were recorded based on the software readout.

[0079] Transmission Electron Microscopy (TEM): Samples for TEM were prepared by casting a drop of the solution onto a carbon film on a copper mesh grid. The samples were then dried in air. The above process was repeated several times to ensure good coverage. Dried samples were visualized using a CM200-FEG instrument operating at 200 kV.

TABLE-US-00001 TABLE 1 Absorbance values measured 7 hours following exposure of endorectal balloons with the plasmonic nanosensor (20 mM C.sub.16TAB concentration) following exposure to different doses of ionizing radiation. The calibration equation used was Absorbance = 0.0092*Dose - 0.0356. The 0 Gy data point is outside the linear range (5-37 Gy) of the nanosensor, and the nanosensor is able to detect X-ray radiation in the linear range. Calculated Dose from Average Radiation Delivered Dose Measured Absorbance the calibration curve Dose Delivered ± S.D (Gy) (A.U) (Gy) (Gy) 0 0.003, 0.002, 0.009 4.19, 4.09, 4.85 4.38 ± 0.41 7.9 0.05, 0.015, 0.045 9.30, 5.50, 8.76 7.85 ± 2.05 10.5 0.061, 0.035, 0.032 10.50, 7.67, 7.35 8.51 ± 1.73

TABLE-US-00002 TABLE 2 X-ray Radiation dose determined using the plasmonic nanosensor placed on 10 an endorectal balloon in a prostate phantom as shown in FIG. 8. The absorbance was determined 2 h after radiation exposure using the equation Absorbance = 0.1597*Dose - 0.0542. 0.5 Gy to 1.5 Gy was the dose range used for determining the calibration curve. A C.sub.16TAB concentration of 2 mM was used in these studies. Capsule No. (Actual Calculated Dose from Average Radiation Dose Delivered Measured Absorbance the calibration curve Dose Delivered ± S.D in Gy) (A.U) (Gy) (Gy) 1 (1) 0.12, 0.138, 0.154 1.09, 1.20, 1.30 1.20 ± 0.11 2 (1) 0.105, 0.154, 0.137 1.00, 1.30, 1.20 1.17 ± 0.16   3 (0.5) 0.016, 0.03, 0.025 0.44, 0.53, 0.50 0.49 ± 0.04

TABLE-US-00003 TABLE 3 Average hydrodynamic diameters of gold nanoparticles formed after irradiation along with their corresponding polydispersity indices. Average Average STD DEV Polydispersity Diameter Diameter Index Surfactant Dose (nm) (nm) (PDI) C.sub.16 20 mM 1 Gy 138.4 5.3 0.2 3 Gy 122.8 1.9 0.2 5 Gy 121.1 20.7 0.3 10 Gy 102.3 13.2 0.2 16 Gy 88.5 12.1 0.2 26 Gy 72.6 4.7 0.2 37 Gy 57.3 4.0 0.3 47 Gy 45.5 3.4 0.3 C.sub.16 2 mM 0.5 Gy 81.9 8.9 0.3 1 Gy 60.2 6.1 0.3 1.5 Gy 48.2 7.3 0.4 2 Gy 42.9 3.8 0.4 2.5 Gy 39.8 3.6 0.4 C.sub.16 4 mM 1 Gy 133.4 10.4 0.2 3 Gy 124.2 5.2 0.2 5 Gy 105.3 6.3 0.2 7.5 Gy 88.6 8.1 0.3 10 Gy 92.6 8.6 0.3 12.5 Gy 81.3 6.9 0.3 15 Gy 74.2 5.5 0.3 26 Gy 57.4 2.4 0.3 37 Gy 32.0 0.4 0.5 47 Gy 22.1 1.3 0.6 C.sub.16 10 mM 1 Gy 126.4 1.5 0.2 3 Gy 127.1 1.6 0.2 5 Gy 124.8 2.1 0.2 10 Gy 124.9 5.0 0.2 16 Gy 106.2 5.4 0.2 26 Gy 72.2 7.1 0.2 37 Gy 59.4 3.3 0.3 47 Gy 50.9 2.3 0.2 C.sub.12 20 mM 1 Gy 141.6 32.2 0.5 3 Gy 112.2 5.3 0.2 5 Gy 75.2 5.0 0.3 10 Gy 40.4 1.0 0.5 16 Gy 23.9 1.1 0.6 26 Gy 15.7 0.8 0.6 37 Gy 17.9 0.7 0.6 47 Gy 21.6 2.7 0.6

TABLE-US-00004 TABLE 4 A list of surfactants which could be potentially be used as an alternative to the current surfactants. Any derivative of the above compounds could also be potentially be used. Molecular Surfactant Name Structure Formula Acetylcholinechloride ≥ 99% (TLC) [00001] C.sub.7H.sub.16ClNO.sub.2 Aliquat ® 336 (2-Aminoethyl)trimethylammonium chloride hydrochloride 99% [00002] C.sub.5H.sub.15ClN.sub.2•HCl Arquad ® 2HT-75 Benzalkonium chloride ≥ 95.0% (T) [00003] Benzalkonium chloride [00004] Benzalkonium chloride solution PharmaGrade. [00005] Benzalkonium chloride solution ≥ 50% (via Cl) 50% in H.sub.2O [00006] Benzyldimethyldecylammonium chloride ≥ 97.0% (AT) [00007] C.sub.19H.sub.34ClN Benzyldimethyldodecylammonium chloride ≥ 99.0% (AT) [00008] C.sub.21H.sub.38ClN Benzyldimethylhexadecylammonium chloride ≥ 97.0% (dried material, AT) [00009] C.sub.25H.sub.46ClN Benzyldimethylhexylammonium chloride ≥ 96.0% (AT) [00010] C.sub.15H.sub.26ClN Benzyldimethyl(2-hydroxyethyl)ammonium chloride ≥ 97.0% (AT) [00011] C.sub.11H.sub.18ClNO Benzyldimethyloctylammonium chloride ≥ 96.0% (AT) [00012] C.sub.17H.sub.30ClN Benzyldimethyltetradecylammonium chloride anhydrous, ≥99.0% (AT) [00013] C.sub.23H.sub.42ClN Benzyldimethyltetradecylammonium chloride dihydrate 98% [00014] C.sub.23H.sub.42ClN•2H.sub.2O Benzyldodecyldimethylammonium bromide ≥ 99.0% (AT) [00015] C.sub.21H.sub.38BrN Benzyldodecyldimethylammonium bromide purum, ≥97.0% (AT) [00016] C.sub.21H.sub.38BrN Benzyltributylammonium bromide ≥ 99.0% [00017] C.sub.19H.sub.34BrN Benzyltributylammonium chloride ≥ 98% [00018] C.sub.19H.sub.34ClN Benzyltributylammonium iodide 97% [00019] C.sub.19H.sub.34IN Benzyltriethylammonium bromide 99% [00020] C.sub.13H.sub.22BrN Benzyltriethylammonium chloride 99% [00021] C.sub.13H.sub.22ClN Benzyltriethylammonium chloride monohydrate 97% [00022] C.sub.13H.sub.22ClN•H.sub.2O Benzyltrimethylammonium bromide 97% [00023] C.sub.10H.sub.16BrN Benzyltrimethylammonium chloride purum, ≥98.0% (AT) [00024] C.sub.10H.sub.16ClN Benzyltrimethylammonium chloride 97% [00025] C.sub.10H.sub.16ClN Benzyltrimethylammonium chloride solution technical, ~60% in H.sub.2O [00026] C.sub.10H.sub.16ClN Benzyltrimethylammonium dichloroiodate 97% [00027] C.sub.10H.sub.16Cl.sub.2IN Benzyltrimethylammonium tetrachloroiodate ≥ 98.0% (AT) [00028] C.sub.10H.sub.16Cl.sub.4IN Benzyltrimethylammonium tribromide purum, ≥97.0% (AT) [00029] C.sub.10H.sub.16Br.sub.3N Benzyltrimethylammonium tribromide 97% [00030] C.sub.10H.sub.16Br.sub.3N Bis(triphenylphosphoranylidene)ammonium chloride 97% [00031] C.sub.36H.sub.30ClNP.sub.2 Boc-D-Lys(2-Cl—Z)—OH ≥ 98.0% (TLC) [00032] C.sub.19H.sub.27ClN.sub.2O.sub.6 (2-Bromoethyl)trimethylammonium bromide 98% [00033] C.sub.5H.sub.13Br.sub.2N (5-Bromopentyl)trimethylammonium bromide 97% [00034] C.sub.8H.sub.19Br.sub.2N (3-Bromopropyl)trimethylammonium bromide 97% [00035] C.sub.6H.sub.15Br.sub.2N S-Butyrylthiocholine iodide puriss., ≥99.0% (AT) [00036] C.sub.9H.sub.20INOS Carbamoylcholine chloride 99% [00037] C.sub.6H.sub.15ClN.sub.2O.sub.2 (3-Carboxypropyl)trimethylammonium chloride technical grade [00038] C.sub.7H.sub.16ClNO.sub.2 Cetyltrimethylammonium chloride solution 25 wt. % in H.sub.2O [00039] C.sub.19H.sub.42ClN Cetyltrimethylammonium hydrogensulfate 99% [00040] C.sub.19H.sub.43NO.sub.4S (2-Chloroethyl)trimethylammonium chloride 98% [00041] C.sub.5H.sub.13Cl.sub.2N (3-Chloro-2-hydroxypropyl)trimethylammonium chloride solution purum, ~65% in H.sub.2O (T) [00042] C.sub.6H.sub.15Cl.sub.2NO (3-Chloro-2-hydroxypropyl)trimethylammonium chloride solution 60 wt. % in H.sub.2O [00043] C.sub.6H.sub.15Cl.sub.2NO Choline chloride ≥ 99% [00044] C.sub.5H.sub.14ClNO Decyltrimethylammonium bromide ≥ 98.0% (NT) [00045] C.sub.13H.sub.30BrN Diallyldimethylammonium chloride ≥ 97.0% (AT) [00046] C.sub.8H.sub.16ClN Diallyldimethylammonium chloride solution 65 wt. % in H.sub.2O [00047] C.sub.8H.sub.16ClN Didecyldimethylammonium bromide 98% [00048] C.sub.22H.sub.48BrN Didodecyldimethylammonium bromide 98% [00049] C.sub.26H.sub.56BrN Dihexadecyldimethylammonium bromide 97% [00050] C.sub.34H.sub.72BrN Dimethyldioctadecylammonium bromide ≥ 98.0% (AT) [00051] C.sub.38H.sub.80BrN Dimethyldioctadecylammonium chloride ≥ 97.0% (AT) [00052] C.sub.38H.sub.80ClN Dimethylditetradecylammonium bromide ≥ 97.0% (NT) [00053] C.sub.30H.sub.64BrN Dimethyloctadecyl[3-(trimethoxysilyl)propyl]ammonium chloride solution 42 wt. % in methanol [00054] C.sub.26H.sub.58ClNO.sub.3Si Dodecylethyldimethylammonium bromide ≥ 98.0% (AT) [00055] C.sub.16H.sub.36BrN Dodecyltrimethylammonium chloride ≥ 99.0% (AT) [00056] C.sub.15H.sub.34ClN Dodecyltrimethylammonium chloride purum, ≥98.0% (AT) [00057] C.sub.15H.sub.34ClN Domiphen bromide 97% [00058] C.sub.22H.sub.40BrNO Ethyltrimethylammonium iodide ≥ 99.0% [00059] C.sub.5H.sub.14IN Girard's reagent T 99% [00060] C.sub.5H.sub.14ClN.sub.3O Glycidyltrimethylammonium chloride technical, ≥90% (calc. based on dry substance, AT) [00061] C.sub.6H.sub.14ClNO Heptadecafluorooctanesulfonic acid tetraethylammonium salt purum, ≥98.0% (T) [00062] C.sub.16H.sub.20F.sub.17NO.sub.3S Heptadecafluorooctanesulfonic acid tetraethylammonium salt 98% [00063] C.sub.16H.sub.20F.sub.17NO.sub.3S Hexadecyl(2-hydroxyethyl)dimethylammonium dihydrogen phosphate solution ~30% in H.sub.2O [00064] C.sub.20H.sub.46NO.sub.5P Hexadecyltrimethylammonium bisulfate purum, ≥97.0% (T) [00065] C.sub.19H.sub.43NO.sub.4S Hexadecyltrimethylammonium bromide ≥ 96.0% (AT) [00066] C.sub.19H.sub.42BrN Hexadecyltrimethylammonium chloride ≥ 98.0% (NT) [00067] C.sub.19H.sub.42ClN Hexadecyltrimethylammonium chloride solution purum, ~25% in H.sub.2O [00068] C.sub.19H.sub.42ClN Hexamethonium bromide ≥ 95.0% (AT) [00069] C.sub.12H.sub.30Br.sub.2N.sub.2 Hexyltrimethylammonium bromide ≥ 98.0% (AT) [00070] C.sub.9H.sub.22BrN Hyamine ® 1622 solution 4 mM in H.sub.2O [00071] Malondialdehyde tetrabutylammonium salt ≥ 96.0% (NT) [00072] C.sub.19H.sub.39NO.sub.2 Methyltrioctylammonium bromide 97% [00073] C.sub.25H.sub.54BrN Methyltrioctylammonium chloride ≥ 97.0% (AT) [00074] C.sub.25H.sub.54ClN Methyltrioctylammonium hydrogen sulfate ≥ 95.0% (T) [00075] C.sub.25H.sub.55NO.sub.4S Methyltrioctylammonium thiosalicylate ≥ 95% (C) [00076] C.sub.32H.sub.59NO.sub.2S Myristyltrimethylammonium bromide 98% (AT) [00077] C.sub.17H.sub.38BrN (4-Nitrobenzyl)trimethylammonium chloride 98% [00078] C.sub.10H.sub.15ClN.sub.2O.sub.2 OXONE ® tetrabutylammonium salt technical, ~1.6% active oxygen basis [00079] Tetrabutylammonium acetate for electrochemical analysis, ≥99.0% [00080] C.sub.18H.sub.39NO.sub.2 Tetrabutylammonium acetate 97% [00081] C.sub.18H.sub.39NO.sub.2 Tetrabutylammonium acetate technical, ≥90% (T) [00082] C.sub.18H.sub.39NO.sub.2 Tetrabutylammonium acetate solution 1.0M in H.sub.2O [00083] C.sub.18H.sub.39NO.sub.2 Tetrabutylammonium benzoate for electrochemical analysis, ≥99.0% [00084] C.sub.23H.sub.41NO.sub.2 Tetrabutylammonium bisulfate puriss., ≥99.0% (T) [00085] C.sub.16H.sub.37NO.sub.4S Tetrabutylammonium bisulfate purum, ≥97.0% (T) [00086] C.sub.16H.sub.37NO.sub.4S Tetrabutylammonium bisulfate solution ~55% in H.sub.2O [00087] C.sub.16H.sub.37NO.sub.4S Tetrabutylammonium bromide ACS reagent, ≥98.0% [00088] C.sub.16H.sub.36BrN Tetrabutylammonium bromide ReagentPlus ®, ≥99.0% [00089] C.sub.16H.sub.36BrN Tetrabutylammonium bromide solution 50 wt. % in H.sub.2O [00090] C.sub.16H.sub.36BrN Tetrabutylammonium chloride ≥ 97.0% (NT) [00091] C.sub.16H.sub.36ClN Tetrabutylammonium chloride hydrate 98% [00092] C.sub.16H.sub.36ClN Tetrabutylammonium cyanate technical [00093] C.sub.17H.sub.36N.sub.2O Tetrabutylammonium cyanide purum, ≥95.0% (AT) [00094] C.sub.17H.sub.36N.sub.2 Tetrabutylammonium cyanide 95% [00095] C.sub.17H.sub.36N.sub.2 Tetrabutylammonium cyanide technical, ≥80% [00096] C.sub.17H.sub.36N.sub.2 Tetrabutylammonium difluorotriphenylsilicate 97% [00097] C.sub.34H.sub.51F.sub.2NSi Tetrabutylammonium difluorotriphenylstannate 97% [00098] C.sub.34H.sub.51F.sub.2NSn Tetrabutylammonium glutaconaldehyde enolate hydrate ≥ 97.0% (T) [00099] C.sub.21H.sub.41NO.sub.2•xH.sub.2O Tetrabutylammonium heptadecafluorooctanesulfonate ≥ 95.0% (H-NMR) [00100] C.sub.24H.sub.36F.sub.17NO.sub.3S Tetrabutylammonium hexafluorophosphate for electrochemical analysis, ≥99.0% [00101] C.sub.16H.sub.36F.sub.6NP Tetrabutylammonium hexafluorophosphate purum, ≥98.0% (CHN) [00102] C.sub.16H.sub.36F.sub.6NP Tetrabutylammonium hexafluorophosphate 98% [00103] C.sub.16H.sub.36F.sub.6NP Tetrabutylammonium hydrogen difluoride solution technical, ~50% in methylene chloride (T) [00104] C.sub.16H.sub.37F.sub.2N Tetrabutylammonium hydrogen difluoride solution ~50% in acetonitrile [00105] C.sub.16H.sub.37F.sub.2N Tetrabutylammonium hydrogensulfate anhydrous, free-flowing, Redi-Dri ™, 97% [00106] C.sub.16H.sub.37NO.sub.4S Tetrabutylammonium hydrogensulfate 97% [00107] C.sub.16H.sub.37NO.sub.4S Tetrabutylammonium iodide for electrochemical analysis, ≥99.0% [00108] C.sub.16H.sub.36IN Tetrabutylammonium iodide ≥ 99.0% (AT) [00109] C.sub.16H.sub.36IN Tetrabutylammonium iodide reagent grade, 98% [00110] C.sub.16H.sub.36IN Tetrabutylammonium methanesulfonate ≥ 97.0% (T) [00111] C.sub.17H.sub.39NO.sub.3S Tetrabutylammonium methoxide solution 20% in methanol (NT) [00112] C.sub.17H.sub.39NO Tetrabutylammonium nitrate purum, ≥97.0% (NT) [00113] C.sub.16H.sub.36N.sub.2O.sub.3 Tetrabutylammonium nitrate 97% [00114] C.sub.16H.sub.36N.sub.2O.sub.3 Tetrabutylammonium nitrite ≥ 97.0% (NT) [00115] C.sub.16H.sub.36N.sub.2O.sub.2 Tetrabutylammonium nonafluorobutanesulfonate ≥ 98.0% [00116] C.sub.20H.sub.36F.sub.9NO.sub.3S Tetrabutylammonium perchlorate for electrochemical analysis, ≥99.0% [00117] C.sub.16H.sub.36ClNO.sub.4 Tetrabutylammonium perchlorate ≥ 98.0% (T) [00118] C.sub.16H.sub.36ClNO.sub.4 Tetrabutylammonium phosphate monobasic puriss., ≥99.0% (T) [00119] C.sub.16H.sub.38NO.sub.4P Tetrabutylammonium phosphate monobasic solution 1.0M in H.sub.2O [00120] C.sub.16H.sub.38NO.sub.4P Tetrabutylammonium phosphate monobasic solution puriss., ~1M in H.sub.2O [00121] C.sub.16H.sub.38NO.sub.4P Tetrabutylammonium succinimide ≥ 97.0% (NT) [00122] C.sub.20H.sub.40N.sub.2O.sub.2 Tetrabutylammonium sulfate solution 50 wt. % in H.sub.2O [00123] C.sub.32H.sub.72N.sub.2O.sub.4S Tetrabutylammonium tetrabutylborate 97% [00124] C.sub.32H.sub.72BN Tetrabutylammonium tetrafluoroborate for electrochemical analysis, ≥99.0% [00125] C.sub.16H.sub.36BF.sub.4N Tetrabutylammonium tetrafluoroborate puriss., ≥99.0% (T) [00126] C.sub.16H.sub.36BF.sub.4N Tetrabutylammonium tetrafluoroborate 99% [00127] C.sub.16H.sub.36BF.sub.4N Tetrabutylammonium tetraphenylborate for electrochemical analysis, ≥99.0% [00128] C.sub.40H.sub.56BN Tetrabutylammonium tetraphenylborate puriss., ≥99.0% (NT) [00129] C.sub.40H.sub.56BN Tetrabutylammonium tetraphenylborate 99% [00130] C.sub.40H.sub.56BN Tetrabutylammonium thiocyanate purum, ≥99.0% (AT) [00131] C.sub.17H.sub.36N.sub.2S Tetrabutylammonium thiocyanate 98% [00132] C.sub.17H.sub.36N.sub.2S Tetrabutylammonium p-toluenesulfonate purum, ≥99.0% (T) [00133] C.sub.23H.sub.43NO.sub.3S Tetrabutylammonium p-toluenesulfonate 99% [00134] C.sub.23H.sub.43NO.sub.3S Tetrabutylammonium tribromide purum, ≥98.0% (RT) [00135] C.sub.16H.sub.36Br.sub.3N Tetrabutylammonium tribromide 98% [00136] C.sub.16H.sub.36Br.sub.3N Tetrabutylammonium trifluoromethanesulfonate ≥ 99.0% (T) [00137] C.sub.17H.sub.36F.sub.3NO.sub.3S Tetrabutylammonium triiodide ≥ 97.0% (AT) [00138] C.sub.16H.sub.36I.sub.3N Tetradodecylammonium bromide ≥ 99.0% (AT) [00139] C.sub.48H.sub.100BrN Tetradodecylammonium chloride ≥ 97.0% (AT) [00140] C.sub.48H.sub.100ClN Tetraethylammonium acetate tetrahydrate 99% [00141] C.sub.10H.sub.23NO.sub.2•4H.sub.2O Tetraethylammonium benzoate for electrochemical analysis, ≥99.0% [00142] C.sub.15H.sub.25NO.sub.2 Tetraethylammonium bicarbonate ≥ 95.0% (T) [00143] C.sub.9H.sub.21NO.sub.3 Tetraethylammonium bistrifluoromethanesulfonimidate for electronic purposes, ≥99.0% [00144] C.sub.10H.sub.20F.sub.6N.sub.2O.sub.4S.sub.2 Tetraethylammonium bromide ReagentPlus ®, 99% [00145] C.sub.8H.sub.20BrN Tetraethylammonium bromide reagent grade, 98% [00146] C.sub.8H.sub.20BrN Tetraethylammonium chloride for electrochemical analysis, ≥99.0% [00147] C.sub.8H.sub.20ClN Tetraethylammonium chloride hydrate [00148] C.sub.8H.sub.20ClN•xH.sub.2O Tetraethylammonium chloride monohydrate ≥ 98.0% [00149] C.sub.8H.sub.20ClN•H.sub.2O Tetraethylammonium cyanate technical [00150] C.sub.9H.sub.20N.sub.2O Tetraethylammonium cyanide purum, ≥95% (AT) [00151] C.sub.9H.sub.20N.sub.2 Tetraethylammonium cyanide 94% [00152] C.sub.9H.sub.20N.sub.2 Tetraethylammonium hexafluorophosphate for electrochemical analysis, ≥99.0% [00153] C.sub.8H.sub.20F.sub.6NP Tetraethylammonium hexafluorophosphate 99% [00154] C.sub.8H.sub.20F.sub.6NP Tetraethylammonium hydrogen sulfate ≥ 99.0% (T) [00155] C.sub.8H.sub.21NO.sub.4S Tetraethylammonium hydrogen sulfate ≥ 98.0% (T) [00156] C.sub.8H.sub.21NO.sub.4S Tetraethylammonium iodide puriss., ≥98.5% (CHN) [00157] C.sub.8H.sub.20IN Tetraethylammonium iodide 98% [00158] C.sub.8H.sub.20IN Tetraethylammonium nitrate ≥ 98.0% (NT) [00159] C.sub.8H.sub.20N.sub.2O.sub.3 Tetraethylammonium tetrafluoroborate for electrochemical analysis, ≥99.0% [00160] C.sub.8H.sub.20BF.sub.4N Tetraethylammonium tetrafluoroborate purum, ≥98.0% (T) [00161] C.sub.8H.sub.20BF.sub.4N Tetraethylammonium tetrafluoroborate 99% [00162] C.sub.8H.sub.20BF.sub.4N Tetraethylammonium p-toluenesulfonate 97% [00163] C.sub.15H.sub.27NO.sub.3S Tetraethylammonium trifluoromethanesulfonate ≥ 98.0% (T) [00164] C.sub.9H.sub.20F.sub.3NO.sub.3S Tetraheptylammonium bromide ≥ 99.0% (AT) [00165] C.sub.28H.sub.60BrN Tetraheptylammonium iodide ≥ 99.0% (AT) [00166] C.sub.28H.sub.60IN Tetrahexadecylammonium bromide purum, ≥98.0% (NT) [00167] C.sub.64H.sub.132BrN Tetrahexadecylammonium bromide 98% [00168] C.sub.64H.sub.132BrN Tetrahexylammonium benzoate solution ~75% in methanol [00169] C.sub.31H.sub.57NO.sub.2 Tetrahexylammonium bromide 99% [00170] C.sub.24H.sub.52BrN Tetrahexylammonium chloride 96% [00171] C.sub.24H.sub.52ClN Tetrahexylammonium hexafluorophosphate ≥ 97.0% (gravimetric) [00172] C.sub.24H.sub.52F.sub.6NP Tetrahexylammonium hydrogensulfate 98% [00173] C.sub.24H.sub.53NO.sub.4S Tetrahexylammonium hydrogensulfate ≥ 98.0% (T) [00174] C.sub.24H.sub.53NO.sub.4S Tetrahexylammonium iodide ≥ 99.0% (AT) [00175] C.sub.24H.sub.52IN Tetrahexylammonium tetrafluoroborate ≥ 97.0% [00176] C.sub.24H.sub.52BF.sub.4N Tetrakis(decyl)ammonium bromide > 99% (titration) [00177] C.sub.40H.sub.84BrN Tetrakis(decyl)ammonium bromide ≥ 99.0% (AT) [00178] C.sub.40H.sub.84BrN Tetramethylammonium acetate technical grade, 90% [00179] C.sub.6H.sub.15NO.sub.2 Tetramethylammonium benzoate electrochemical grade, ≥98.5% (NT) [00180] C.sub.11H.sub.17NO.sub.2 Tetramethylammonium bis(trifluoromethanesulfonyl)imide 97% [00181] C.sub.6H.sub.12F.sub.6N.sub.2O.sub.4S.sub.2 Tetramethylammoniumbisulfate hydrate ≥ 98.0% (calc. on dry  •xH.sub.2O C.sub.4H.sub.13NO.sub.4S•xH.sub.2O substance, T) Tetramethylammonium bromide ACS reagent ≥ 98.0% [00182] C.sub.4H.sub.12BrN Tetramethylammonium bromide 98% [00183] C.sub.4H.sub.12BrN Tetramethylammonium bromide for electrochemical analysis, ≥99.0% [00184] C.sub.4H.sub.12BrN Tetramethylammonium chloride for electrochemical analysis, ≥99.0% [00185] C.sub.4H.sub.12ClN Tetramethylammonium chloride purum, ≥98.0% (AT) [00186] C.sub.4H.sub.12ClN Tetramethylammonium chloride reagent grade, ≥98% [00187] C.sub.4H.sub.12ClN Tetramethylammonium chloride solution for molecular biology [00188] Tetramethylammonium formate solution 30 wt. % in H.sub.2O, ≥99.99% trace metals basis [00189] C.sub.5H.sub.13NO.sub.2 Tetramethylammonium hexafluorophosphate ≥ 98.0% (gravimetric) [00190] C.sub.4H.sub.12F.sub.6NP Tetramethylammonium hydrogen sulfate monohydrate crystallized,  O C.sub.4H.sub.13NO.sub.4S•H.sub.2O ≥98.0% (T) Tetramethylammonium hydrogensulfate hydrate 98%  O C.sub.4H.sub.13NO.sub.4S•xH.sub.2O Tetramethylammonium iodide 99% [00191] C.sub.4H.sub.12IN Tetramethylammonium nitrate 96% (CH.sub.3).sub.4N(NO.sub.3) C.sub.4H.sub.12N.sub.2O.sub.3 Tetramethylammonium silicate solution 15-20 wt. % in H.sub.2O, C.sub.4H.sub.13NO.sub.5Si.sub.2 ≥99.99% trace metals basis Tetramethylammonium sulfate hydrate [00192] C.sub.8H.sub.24N.sub.2O.sub.4S•xH.sub.2O Tetramethylammonium tetrafluoroborate purum, ≥98.0% (T) [00193] C.sub.4H.sub.12BF.sub.4N Tetramethylammonium tetrafluoroborate 97% [00194] C.sub.4H.sub.12BF.sub.4N Tetramethylammonium tribromide purum, ≥98.0% (AT) [00195] C.sub.4H.sub.12Br.sub.3N Tetraoctadecylammonium bromide purum, ≥98.0% (NT) [00196] C.sub.72H.sub.148BrN Tetraoctadecylammonium bromide 98% [00197] C.sub.72H.sub.148BrN Tetraoctylammonium bromide purum, ≥98.0% (AT) [00198] C.sub.32H.sub.68BrN Tetraoctylammonium bromide 98% [00199] C.sub.32H.sub.68BrN Tetraoctylammonium chloride ≥ 97.0% (AT) [00200] C.sub.32H.sub.68ClN Tetrapentylammonium bromide ≥ 99% [00201] C.sub.20H.sub.44NBr Tetrapentylammonium chloride 99% [00202] C.sub.20H.sub.44ClN Tetrapropylammonium perchlorate ≥ 98.0% (T) [00203] C.sub.12H.sub.28ClNO.sub.4 Tetrapropylammonium bromide for electrochemical analysis, ≥99.0% [00204] C.sub.12H.sub.28BrN Tetrapropylammonium bromide purum, ≥98.0% (AT) [00205] C.sub.12H.sub.28BrN Tetrapropylammonium bromide 98% [00206] C.sub.12H.sub.28BrN Tetrapropylammonium chloride 98% [00207] C.sub.12H.sub.28ClN Tetrapropylammonium iodide ≥ 98% [00208] C.sub.12H.sub.28IN Tetrapropylammonium tetrafluoroborate ≥ 98.0% [00209] C.sub.12H.sub.28BF.sub.4N Tributylammonium pyrophosphate [00210] Tributylmethylammonium bromide ≥ 98.0% [00211] C.sub.13H.sub.30BrN Tributylmethylammonium chloride ≥ 98.0% (T) [00212] C.sub.13H.sub.30ClN Tributylmethylammonium chloride solution 75 wt. % in H.sub.2O [00213] C.sub.13H.sub.30ClN Tributylmethylammonium methyl sulfate ≥ 95% [00214] C.sub.14H.sub.33NO.sub.4S Tricaprylylmethylammonium chloride mixture of C.sub.8-C.sub.10 C.sub.8 is dominant [00215] Tridodecylmethylammonium chloride purum, ≥97.0% (AT) [00216] C.sub.37H.sub.78ClN Tridodecylmethylammonium chloride 98% [00217] C.sub.37H.sub.78ClN Tridodecylmethylammonium iodide 97% [00218] C.sub.37H.sub.78IN Triethylhexylammonium bromide 99% [00219] C.sub.12H.sub.28BrN Triethylmethylammonium bromide ≥ 99.0% [00220] C.sub.7H.sub.18BrN Triethylmethylammonium chloride 97% [00221] C.sub.7H.sub.18ClN Trihexyltetradecylammonium bromide ≥ 97.0% (T) [00222] C.sub.32H.sub.68BrN Trimethyloctadecylammonium bromide purum, ≥97.0% (AT) [00223] C.sub.21H.sub.46BrN Trimethyloctadecylammonium bromide 98% [00224] C.sub.21H.sub.46BrN Trimethyloctylammonium bromide ≥ 98.0% (AT) [00225] C.sub.11H.sub.26BrN Trimethyloctylammonium chloride ≥ 97.0% (AT) [00226] C.sub.11H.sub.26ClN Trimethylphenylammonium bromide 98% [00227] C.sub.9H.sub.14BrN Trimethylphenylammonium chloride ≥ 98% [00228] C.sub.9H.sub.14ClN Trimethylphenylammonium tribromide 97% [00229] C.sub.9H.sub.14Br.sub.3N Trimethyl-tetradecylammonium chloride ≥ 98.0% (AT) [00230] C.sub.17H.sub.38ClN (Vinylbenzyl)trimethylammonium chloride 99% [00231] C.sub.12H.sub.18ClN N-(Allyloxycarbonyloxy)succinimide 96% [00232] C.sub.8H.sub.9NO.sub.5 3-Benzyl-5-(2-hydroxyethyl)-4-methylthiazolium chloride purum, ≥99.0% (AT) [00233] C.sub.13H.sub.16ClNOS 3-Benzyl-5-(2-hydroxyethyl)-4-methylthiazolium chloride 98% [00234] C.sub.13H.sub.16ClNOS 1-Butyl-2,3-dimethylimidazolium chloride ≥ 97.0% (HPLC/AT) [00235] C.sub.9H.sub.17ClN.sub.2 1-Butyl-2,3-dimethylimidazolium hexafluorophosphate [00236] C.sub.9H.sub.17F.sub.6N.sub.2P 1-Butyl-2,3-dimethylimidazolium tetrafluoroborate ≥ 97.0% [00237] C.sub.9H.sub.17BF.sub.4N.sub.2 1,3-Didecyl-2-methylimidazolium chloride 96% [00238] C.sub.24H.sub.47ClN.sub.2 1,1-Dimethyl-4-phenylpiperazinium iodide ≥ 99.0% (AT) [00239] C.sub.12H.sub.19IN.sub.2 1-Ethyl-2,3-dimethylimidazolium ethyl sulfate BASF quality, ≥94.5% (HPLC) [00240] C.sub.9H.sub.18N.sub.2O.sub.4S 3-Ethyl-5-(2-hydroxyethyl)-4-methylthiazolium bromide ≥ 98% [00241] C.sub.8H.sub.14BrNOS Hexadecylpyridinium bromide [00242] C.sub.21H.sub.38BrN Hexadecylpyridinium bromide ≥ 97.0% [00243] C.sub.21H.sub.38BrN Hexadecylpyridinium chloride monohydrate BioXtra, 99.0-102.0% [00244] C.sub.21H.sub.38ClN•H.sub.2O 5-(2-Hydroxyethyl)-3,4-dimethylthiazolium iodide 98% [00245] C.sub.7H.sub.12INOS 1-Methylimidazolium hydrogen sulfate 95% [00246] C.sub.4H.sub.6N.sub.2•H.sub.2SO.sub.4 Methyl viologen dichloride hydrate 98% [00247] C.sub.12H.sub.14Cl.sub.2N.sub.2•xH.sub.2O 1,2,3-Trimethylimidazolium methyl sulfate BASF quality, 95% [00248] C.sub.7H.sub.14N.sub.2O.sub.4S DL-α-Tocopherol methoxypolyethylene glycol succinate DL-α-Tocopherol methoxypolyethylene glycol succinate solution 2 wt. % in H2O DL-α-Tocopherol methoxypolyethylene glycol succinate solution 5 wt. % in H2O Aliquat ® HTA-1 High-Temperature Phase Transfer Catalyst, 30- 35% in H.sub.2O Bis[tetrakis(hydroxymethyl)phosphonium] sulfate solution technical, 70-75% in H.sub.2O (T) [00249] C.sub.8H.sub.24O.sub.12P.sub.2S Dimethyldiphenylphosphonium iodide purum, ≥98.0% (AT) [00250] C.sub.14H.sub.16IP Dimethyldiphenylphosphonium iodide 98% [00251] C.sub.14H.sub.16IP Methyltriphenoxyphosphonium iodide 96% [00252] C.sub.19H.sub.18IO.sub.3P Methyltriphenoxyphosphonium iodide technical, ≥96.0% (AT) [00253] C.sub.19H.sub.18IO.sub.3P Tetrabutylphosphonium bromide 98% [00254] C.sub.16H.sub.36BrP Tetrabutylphosphonium chloride 96% [00255] C.sub.16H.sub.36ClP Tetrabutylphosphonium hexafluorophosphate for electrochemical analysis, ≥99.0% [00256] C.sub.16H.sub.36F.sub.6P.sub.2 Tetrabutylphosphonium methanesulfonate ≥ 98.0% (NT) [00257] C.sub.17H.sub.39O.sub.3PS Tetrabutylphosphonium tetrafluoroborate for electrochemical analysis, ≥99.0% [00258] C.sub.16H.sub.36BF.sub.4P Tetrabutylphosphonium p-toluenesulfonate ≥ 95% (NT) [00259] C.sub.23H.sub.43O.sub.3PS Tetrakis(hydroxymethyl)phosphonium chloride solution 80% in H.sub.2O [00260] C.sub.4H.sub.12ClO.sub.4P Tetrakis(hydroxymethyl)phosphonium chloride solution technical, ~80% in H.sub.2O [00261] C.sub.4H.sub.12ClO.sub.4P Tetrakis[tris(dimethylamino)phosphoranylidenamino]phosphonium chloride ≥ 98.0% [00262] C.sub.24H.sub.72ClN.sub.16P.sub.5 Tetramethylphosphonium bromide 98% [00263] C.sub.4H.sub.12BrP Tetramethylphosphonium chloride 98% [00264] C.sub.4H.sub.14ClP Tetraphenylphosphonium bromide 97% [00265] C.sub.24H.sub.20BrP Tetraphenylphosphonium chloride for the spectrophotometric det. of Bi, Co, ≥97.0% [00266] C.sub.24H.sub.20ClP Tetraphenylphosphonium chloride 98% [00267] C.sub.24H.sub.20ClP Tributylhexadecylphosphonium bromide 97% [00268] C.sub.28H.sub.60BrP Trihexyltetradecylphosphonium bis(2,4,4-trimethylpentyl) phosphinate ≥95.0% [00269] C.sub.48H.sub.102O.sub.2P.sub.2 Trihexyltetradecylphosphonium bromide ≥ 95% [00270] C.sub.32H.sub.68BrP Trihexyltetradecylphosphonium chloride ≥ 95.0% (NMR) [00271] C.sub.32H.sub.68ClP Trihexyltetradecylphosphonium dicyanamide ≥ 95% [00272] C.sub.34H.sub.68N.sub.3P ALKANOL ® 6112 surfactant Adogen ® 464 Brij ® 52 main component: diethylene glycol hexadecyl ether Brij ® 52 average M.sub.n~330 Brij ® 93 average M.sub.n~357 Brij ® S2 main component: diethylene glycol octadecyl ether Brij ® S 100 average M.sub.n~4,670 Brij ® 58 average M.sub.n~1124 Brij ® C10 average M.sub.n~683 Brij ® L4 average M.sub.n~362 Brij ® O10 average M.sub.n~709 BRIJ ® O20 average M.sub.n~1,150 Brij ® S10 average M.sub.n~711 Brij ® S20 Ethylenediamine tetrakis(ethoxylate-block-propoxylate) tetrol average M.sub.n~7,200 Ethylenediamine tetrakis(ethoxylate-block-propoxylate) tetrol average M.sub.n~8,000 Ethylenediamine tetrakis(propoxylate-block-ethoxylate) tetrol average M.sub.n~3,600 IGEPAL ® CA-520 average M.sub.n~427 IGEPAL ® CA-720 average M.sub.n~735 IGEPAL ® CO-520 average M.sub.n 441 IGEPAL ® CO-630 average M.sub.n 617 IGEPAL ® CO-720 average M.sub.n~749 IGEPAL ® CO-890 average M.sub.n~1,982 IGEPAL ® DM-970 MERPOL ® DA surfactant 60 wt. % in water: isobutanol (ca. 50:50) MERPOL ® HCS surfactant MERPOL ® OJ surfactant MERPOL ® SE surfactant MERPOL ® SH surfactant MERPOL ® A surfactant Poly(ethylene glycol) sorbitan tetraoleate Poly(ethylene glycol) sorbitol hexaoleate Poly(ethylene glycol) (12) tridecyl ether mixture of C.sub.11 to C.sub.14 iso-alkyl ethers with C.sub.13 iso-alkyl predominating Poly(ethylene glycol) (18) tridecyl ether mixture of C.sub.11 to C.sub.14 iso-alkyl ethers with C.sub.13 iso-alkyl predominating Polyethylene-block-poly(ethylene glycol) average M.sub.n~575 Polyethylene-block-poly(ethylene glycol) average M.sub.n~875 Polyethylene-block-poly(ethylene glycol) average M.sub.n~920 Polyethylene-block-poly(ethylene glycol) average M.sub.n~1,400 Sorbitan monopalmitate 2,4,7,9-Tetramethyl-5-decyne-4,7-diol ethoxylate average M.sub.n 670 2,4,7,9-Tetramethyl-5-decyne-4,7-diol, mixture of (±) and meso 98% Triton ™ N-101, reduced Triton ™ X-100 Triton ™ X-100 reduced Triton ™ X-114, reduced reduced, ≥99% Triton ™ X-114, reduced reduced Triton ™ X-405, reduced reduced TWEEN ® 20 average M.sub.n~1,228 TWEEN ® 40 viscous liquid TWEEN ® 60 nonionic detergent TWEEN ® 85 indicates data missing or illegible when filed