System and method for detecting contaminants in a fluid sample - Patents.com

Abstract

A system for detecting contaminants in a fluid sample is disclosed. The system includes a colloidal dispersion circuit having a reservoir containing a colloidal dispersion having colloidal particles capable of exhibiting localized surface plasmon resonance ("LSPR particles"), a Raman spectrometer / flow cell, and a pump for circulating the colloidal dispersion through the colloidal dispersion circuit. A colloidal dispersion level sensor measures the extent of colloidal dispersion in the colloidal dispersion circuit. A permeable valve redirects the colloidal dispersion in the colloidal dispersion circuit through an ultrafiltration membrane that has a pore size smaller than the LSPR particles, thereby preventing the LSPR particles from passing through. A sample can be introduced into the colloidal dispersion circuit through a fluid sample injection valve. A processor is connected to the Raman spectrometer / flow cell, the pump, the permeable valve, the colloidal dispersion level sensor, and the fluid sample injection port. The processor performs a number of steps to analyze the sample.

Description

[Technical field]

[0001] The present invention relates to a system and method for detecting contaminants in a fluid.

[0002] [Related Applications] This application claims priority to U.S. Provisional Application No. 63 / 236,445, filed August 24, 2021, and U.S. Non-Provisional Application No. 17 / 554,841, filed December 17, 2021, the entire contents of both of which are incorporated herein by reference. [Background technology]

[0003] Many industries require very high purity chemicals. Liquid chemicals that require detection limits of parts per billion (ppb) or less use state-of-the-art analytical techniques such as inductively coupled plasma mass spectrometry (ICP-MS) or inductively coupled plasma optical emission spectrometry (ICP-OES), chromatographic techniques such as high performance liquid chromatography (HPLC), headspace gas chromatography (headspace GC), and similar advanced analytical methods. These techniques often require significant sample preparation to complete the analysis. Many industries need to measure liquid chemicals in-process, in-line, or in-situ. Examples include, but are not limited to, chemical manufacturing systems, chemical blending systems, chemical distribution systems, chemical containers, and processing tools that use such chemicals in separate processes. Processing tools that use liquid chemicals may include, but are not limited to, cleaning, etching, spraying, coating, semiconductor processing, polishing, and the like. Biotechnology and pharmacological applications may also require ultra-high purity chemicals both in-line and in-situ. Many advanced analytical techniques are either very expensive to sample and measure in-line or are very large scale and impractical to establish in chemical processes. Therefore, there is a need for miniature in-process, in-line and / or in-situ chemical monitoring systems capable of detecting and identifying chemicals and impurities at sub-ppm levels.

[0004] Enhanced Raman spectroscopy, such as surface-enhanced Raman spectroscopy (SERS), resonance Raman spectroscopy, surface-enhanced resonance Raman spectroscopy (SERRS), and similar analytical techniques, can detect the concentration levels of required chemicals and impurities, as well as identify the chemical nature of the chemicals and impurities. Disclosed herein is a device capable of in-line, in-process, and in-situ chemical analysis that uses Raman resonance to spectroscopically detect and identify impurities and low concentration chemicals in liquid chemical processing. The device can also function as an offline analytical tool. Summary of the Invention

[0005] A system for effectively detecting contaminants in a fluid sample is disclosed. The system includes a colloidal dispersion circuit having a reservoir containing a colloidal dispersion having colloidal particles capable of exhibiting localized surface plasmon resonance ("LSPR particles"), a Raman spectrometer / flow cell, and a pump for circulating the colloidal dispersion through the colloidal dispersion circuit. A colloidal dispersion level sensor measures the degree of colloidal dispersion in the colloidal dispersion circuit. A permeable valve redirects the colloidal dispersion in the colloidal dispersion circuit through an ultrafiltration membrane that has a pore size smaller than the LSPR particles, thereby preventing the LSPR particles from passing through. A sample can be introduced into the colloidal dispersion circuit through a fluid sample injection valve. A processor is connected to the Raman spectrometer / flow cell, the pump, the permeable valve, the colloidal dispersion level sensor, and the fluid sample injection port. The processor performs the following steps: (a) starting the pump; (b) reading a first signal from the Raman spectrometer / flow cell, where the signal is based on Raman scattering; (c) opening the permeable valve to redirect the colloidal dispersion to the ultrafiltration membrane to reach a predetermined colloidal dispersion level indicated by the colloidal dispersion level sensor; (d) opening the fluid sample injection valve, thereby introducing the fluid sample into the colloidal dispersion circuit; (e) reading a second signal from the Raman spectrometer / flow cell, where the second signal is based on Raman scattering; and (f) determining the presence of a contaminant in the fluid sample based on the first and second signals.

[0006] The colloidal dispersion circuit may also include a reservoir valve between the reservoir and the Raman spectrometer / flow cell. The reservoir valve may be connected to the processor such that the processor can open the reservoir valve during step (b). After step (c), the processor may adjust the permeation valve to maintain a predetermined colloidal dispersion level.

[0007] The system may also include a wash valve that introduces a wash fluid from a wash fluid reservoir into the colloidal dispersion circuit. The wash valve may be connected to the processor. The processor may further close the fluid sample injection valve, open the permeate valve, and open the wash valve.

[0008] The system may include a database coupled to the processor. The database includes data relating a plurality of spectra to a plurality of contaminants, and the processor may access the database to identify a type of contaminant based on the database data. The processor may also identify an amount of the contaminant based on the strength of the second signal.

[0009] Also disclosed is a method of detecting a contaminant in a sample, the method comprising the steps of: (a) introducing a colloidal dispersion of a liquid and colloidal localized surface plasmon resonance ("LSPR") particles, (b) exposing the colloidal dispersion to electromagnetic radiation sufficient to induce surface-enhanced Raman scattering in the colloidal dispersion of LSPR particles, (c) measuring the scattered electromagnetic radiation from step (b), (d) introducing a sample into the colloidal dispersion, (e) exposing the sample / colloidal dispersion mixture to electromagnetic radiation sufficient to induce surface-enhanced Raman scattering in the colloidal dispersion of LSPR particles, (f) measuring the scattered electromagnetic radiation from step (e), and (g) detecting the presence of a contaminant in the sample by comparing the measurements from step (c) to the measurements from step (f).

[0010] The method may further comprise concentrating the LSPR particles after step (a) by permeating liquid through the colloidal dispersion.

[0011] The method may also include, after step (a), concentrating the LSPR particles to a predetermined colloidal dispersion level by permeating only liquid from the colloidal dispersion, and permeating the sample / colloidal dispersion mixture during steps (d), (e), and (f) to maintain the predetermined colloidal dispersion level.

[0012] The method may further include comparing the measurements from steps (c) and (f) to a database containing data associating a plurality of spectra with a plurality of contaminants, and identifying the type of contaminant based on the comparison in step (h).

[0013] The method may include determining a concentration or amount of the contaminant based on the intensity of the measurement in step (f).

[0014] Further embodiments, alternatives, and variations that will be apparent to those skilled in the art are also disclosed herein and are specifically intended to be included as part of the present invention. The present invention is described solely in terms of the claims permitted by the Patent Office in this or a related application, and the following summary description of specific examples in no way limits, defines, or otherwise establishes the scope of legal protection.

[0015] The present invention can be better understood with reference to the accompanying drawings. The components in the drawings are not necessarily to scale, with emphasis instead being placed on clearly illustrating exemplary aspects of the present invention. In the drawings, like reference numbers indicate corresponding parts throughout the various views and / or embodiments. Furthermore, various features of the various disclosed embodiments can be combined to form further embodiments that are part of the present disclosure. It will be understood that certain components and details may not be present in the drawings to help more clearly explain the present invention. [Brief description of the drawings]

[0016] [Figure 1] FIG. 1 illustrates a system for detecting contaminants in a fluid sample. [Diagram 2] FIG. 1 is a diagram of the starting configuration of the system. [Diagram 3] FIG. 1 is a diagram of a configuration in which the system is reaching a predetermined colloidal dispersion level. [Figure 4] FIG. 13 is a diagram of the configuration in which the system has reached a predetermined colloidal dispersion level. [Diagram 5] FIG. 1 is a diagram of a non-steady state sample analysis setup. [Figure 6] FIG. 1 is a diagram of a steady-state sample analysis setup. [Figure 7] 5 shows the concentration of colloidal localized plasmon resonance particles in the configurations shown in FIGS. [Figure 8] FIG. 1 is a diagram of the cleaning configuration of the system. [Figure 9] FIG. 1 illustrates a method for detecting contaminants in a sample. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0017] Reference will now be made to some specific examples of the invention, including the best mode contemplated by the inventors for carrying out the invention. Examples of these specific embodiments are illustrated in the accompanying drawings. While the invention will be described in conjunction with these specific embodiments, it will be understood that it is not intended to limit the invention to the embodiments described or illustrated. On the contrary, it is intended to cover alternatives, modifications, and equivalents as may be included within the spirit and scope of the invention as defined by the appended claims.

[0018] In the following description, numerous specific details are set forth to provide a thorough understanding of the invention. Certain exemplary embodiments of the invention may be practiced without some or all of these specific details. In other cases, process operations well known to those skilled in the art have not been described in detail so as not to unnecessarily obscure the invention. Various techniques and mechanisms of the invention may be described in the singular for clarity. However, it should be noted that some embodiments include multiple iterations of a technique or multiple mechanisms unless otherwise stated. Similarly, various steps of the methods illustrated and described herein may not necessarily be performed in the order shown, or at all, in certain embodiments. Thus, some implementations of the methods discussed herein may include more or fewer steps than those shown or described. Furthermore, the techniques and mechanisms of the invention may describe connections, relationships, or interactions between two or more entities. It should be noted that a connection or relationship between entities does not necessarily imply a direct, uninterrupted connection, since various other entities or processes may exist or occur between any two entities. Thus, a connection shown does not necessarily imply a direct, uninterrupted connection, unless otherwise stated.

[0019] The following list of exemplary features corresponds to the attached drawings and is provided for ease of reference, with like reference numerals indicating corresponding features throughout the specification and drawings. [Explanation of symbols]

[0020] 5. Fluid Contaminant Detection System 7. Colloidal dispersion circulation path 8. Pump 10 Reservoir 12 Colloidal dispersion level sensor 15 Raman spectrometer / flow cell 20 Ultrafiltration membrane 22 Permeate liquid 25 Permeation Liquid Reservoir 25 30 Fluid Samples 35 Colloidal Localized Surface Plasmon Resonance ("LSPR") Particles 37 Processors 45 Ultrafiltration membrane permeable valve 50 Permeation channel 55 Reservoir valve 60 Fluid sample valve / injection port 65 Fluid sample injection channel 70 Cleaning fluid reservoir 75 Cleaning valve 900 Method for detecting contaminants in a sample 905~970 Steps of Method 900

[0021] Raman spectroscopy is a non-destructive chemical analysis technique that provides detailed information about chemical structure, phases and polymorphism, crystallinity and intermolecular interactions. Raman spectroscopy is based on the interaction of light with chemical bonds in materials. Raman spectroscopy is a light scattering technique in which molecules scatter incident light from a high intensity laser source. Most of the scattered light is at the same wavelength (or color) as the laser source and does not provide any useful information, this is called Rayleigh scattering. However, a small amount of light (typically 0.0000001%) is scattered at different wavelengths (or colors), which depends on the chemical structure of the analyte, this is called Raman scattering.

[0022] A Raman spectrum is characterized by multiple peaks, which indicate the intensity and wavelength position of the Raman scattered light, each peak corresponding to a specific molecular bond vibration, including individual bonds such as C-C, C=C, NO, CH, etc., bond groups such as benzene ring breathing vibrational modes, polymer chain vibrations, lattice modes, etc.

[0023] Localized surface plasmons (LSPs) are formed in nanoparticles with sizes comparable to or smaller than the excitation wavelength due to the confinement of surface plasmons. When conductive nanoparticles such as gold or silver or similar nanoscale structures are excited by light, the oscillating electric field causes the conduction electrons to oscillate coherently. This coherence enhances the localization of visible light by orders of magnitude.

[0024] A plasmon is a discrete measure (like a photon) of electron vibration in a conductive material. When light interacts with an appropriate material, the oscillation of electrons in the conduction band creates surface plasmons. For nanoparticles that are smaller than the incident frequency of the light, the plasmon is confined to the surface of the nanoparticle and is called a localized surface plasmon. When the frequency of the light matches the natural resonant frequency of the nanoparticle, localized surface plasmon resonance occurs at the surface of the nanoparticle. Localized surface plasmon resonance ("LSPR") results in a very strong electromagnetic signal at the surface. The resonant frequency and the strong electromagnetic field can be used to detect and characterize molecules at or near the surface of the particle. Surface-enhanced Raman spectroscopy uses these effects to characterize very low molecular concentrations at or near the surface of a nanoparticle.

[0025] LSPR nanostructures include, but are not limited to, coated or layered particles containing elements capable of LSPR, nanoparticles with structures that improve their resonance, nanoshells, nanorods, nanowires, nanoclusters, nanostars, aggregated nanoparticles, cocoon-shaped nanoparticles, nanosheets, and similar shapes and structures that can improve or tune the resonance properties of a material, such as metal nanoparticles, metal alloy nanoparticles, doped and undoped semiconductor nanoparticles, metal oxide nanoparticles, and composites of these types of materials, typically between 3 and 1000 nm in size.

[0026] The contaminant detection system disclosed herein introduces colloidal LSPR particles, typically nanoscale structures (such as gold or silver) dispersed in a liquid, to flow through a permeable ultrafiltration membrane that is selected based on the size and characteristics of the LSPR particles. Circulation through the permeable membrane concentrates the LSPR material by removing only dissolved materials that are small enough to pass through the liquid and the filter membrane, thus allowing the LSPR nanoscale structures to increase in concentration as they are retained within the colloidal dispersion circulation path. As the LSPR particles concentrate, the nanoscale structures move closer to each other in the liquid. Once an optimal concentration of the LSPR material is achieved, the Raman signal can be measured using a Raman spectrometer / flow cell that uses a laser to excite the nanostructures into a resonant state. Thus, the volume under investigation in the Raman spectrometer / flow cell exhibits (SERS) surface-enhanced Raman spectra, resonance Raman spectra, and / or (SERRS) surface-enhanced resonance Raman spectra. SERS, SERRS, and resonance Raman spectroscopy all produce a significant increase in Raman scattering of materials within the volume under investigation, allowing the spectrometer to increase the detection limit by many orders of magnitude. In effect, the enhanced resonance of the LSPR nanoparticles acts like a spotlight illuminating adjacent adsorbed contaminants that would otherwise go undetected or unseen in conventional techniques. Once the optimal concentration of LSPR particles is achieved, sampling can be performed in-line by optimizing the permeability of the ultrafiltration membrane with the introduction of the sample. Alternatively, for offline measurements, the sample can be injected into the colloidal dispersion circulation path of the device.

[0027] 1, a fluid contaminant detection system 5 of the present invention comprises a colloidal dispersion circuit 7, a colloidal dispersion level sensor 12, a permeable valve 45, a fluid sample injection valve 60 configured to introduce a fluid sample 30 into the colloidal dispersion circuit 7, and a processor 37. The colloidal dispersion circuit 7 itself comprises a reservoir 10 that holds or contains a colloidal dispersion having colloidal localized surface plasmon resonance (hereinafter LSPR) particles 35, a Raman spectrometer or flow cell 15, and a pump 8 that circulates the colloidal dispersion. The permeable valve 45 is configured to redirect the colloidal dispersion in the colloidal dispersion circuit 7 through an ultrafiltration membrane 20. The ultrafiltration membrane 20 has a pore size smaller than the LSPR particles 35 to prevent the LSPR particles 35 from passing through. The liquid in the reservoir 10 containing the LSPR particles 35 forms a colloidal dispersion, which can then be filtered by the ultrafiltration membrane 20, so that the concentration of the LSPR particles 35 in the reservoir 10 can be adjusted to a desired level by the fluid contaminant detection system 5, by filtering the permeate liquid 22 out of the circulation and into the permeate reservoir 25. The processor 37 reads a signal from the colloidal dispersion level sensor 12 to determine the degree of colloidal dispersion in the colloidal dispersion circulation 7, although the colloidal dispersion level sensor 12 is shown in FIG. 1 as being located at or near the reservoir 10, it can be located elsewhere along the colloidal dispersion circulation 7 without affecting its functionality and without departing from the scope of the present invention. The fluid contaminant detection system 5 may optionally include a reservoir valve 55 in the colloidal dispersion circulation 7 to better regulate the flow of the circulation fluid containing the colloidal dispersion back to the reservoir 10. Colloidal dispersion circuit 7 , represented in FIG. 1 by a dashed line, refers to the path of the circulating fluid flowing from reservoir 10 through pump 8 to Raman spectrometer or flow cell 15 and back to reservoir 10 through reservoir valve 55 .When the ultrafiltration membrane permeate valve 45 is opened, a portion of the circulating fluid may also flow through the valve 45 and the ultrafiltration membrane 20 to the reservoir valve 55 and reservoir 10, which path is also included as part of the colloidal dispersion circuit 7 when the permeate valve 45 is in the open position. Optionally, the system 5 may include a wash valve 75 that introduces a wash fluid from a wash fluid reservoir 70 into the colloidal dispersion circuit 7 after analysis of the fluid sample 30 is completed.

[0028] The processor 37 of the fluid contaminant detection system 5 is connected to the pump 8 , the Raman spectrometer / flow cell 15 , the permeable valve 45 , the colloidal dispersion level sensor 12 , and the fluid sample injection port 60 . The processor 37 is configured to perform the following steps: (a) start the pump 8; (b) read a first signal from the Raman spectrometer / flow cell 15, the signal being based on Raman scattering; (c) open the permeable valve 45 to divert the colloidal dispersion to the ultrafiltration membrane 20 to reach a predetermined colloidal dispersion level, as indicated by the colloidal dispersion level sensor 12; (d) open the fluid sample injection valve 60, thereby introducing the fluid sample 30 into the colloidal dispersion circuit 7; (e) read a second signal from the Raman spectrometer / flow cell 15, the second signal being based on Raman scattering; and (f) determine the presence of a contaminant in the fluid sample 30 based on the first signal obtained in step (b) and the second signal obtained in step (e). As shown in FIG. 1, if system 5 includes optional reservoir valve 55, reservoir valve 55 is connected between reservoir 10 and Raman spectrometer or flow cell 15, and processor 37 is further configured to open reservoir valve 55 during step (b) when reading out a Raman scattering signal from Raman spectrometer / flow cell 15.

[0029] 2, the system 5 is shown in a starting configuration when the reservoir 10 is full of a liquid (i.e., a colloidal dispersion) containing LSPR particles 35, and the fluid sample 30 has not yet been introduced into the colloidal dispersion circuit 7 via the fluid sample valve or injection port 60. The fluid sample valve / injection port 60 and the permeation valve 45 are both closed. To achieve an ideal resonance for detecting minute amounts or concentrations of contaminants in the sample liquid 30, the system 5 is operated to adjust the distance between the LSPR particles by permeating the colloidal dispersion and removing the permeation liquid 22 from the circuit 7, thereby increasing the concentration of the LSPR particles 35 in the colloidal dispersion and adjusting to optimize the signal strength. The processor 37 may take a readout from the Raman spectrometer / flow cell 15 to determine if the optimal concentration has been achieved. Furthermore, depending on the type and concentration of contaminants expected in the fluid sample, the optimal concentration of the LSPR particles in the colloidal dispersion may vary.

[0030] FIG. 3 shows the system state in a configuration where the fluid contaminant detection system 5 is reaching a desired predetermined concentration so that the system 5 can read a baseline signal at optimal resonance before the fluid sample 30 is introduced. The ultrafiltration permeable membrane valve 45 is open, so that the liquid in the colloidal dispersion passes through the ultrafiltration membrane 20. Because the membrane 20 has a smaller pore size than the LSPR particles 35, the permeate liquid 22 that passes through the membrane 20 and enters the permeate liquid reservoir 25 does not contain any significant amount of LSPR particles 35. The optional reservoir valve 55 may be opened or closed to assist in this process, with the purpose of achieving optimal resonance and obtaining a baseline readout for Raman scattering. The optimal concentration may be detected from the Raman spectrometer / flow cell 15, or may be detected by the colloidal dispersion level sensor 12, with or without information from a database accessed by the processor 37.

[0031] 4 illustrates the fluid contaminant detection system 5 when a desired predetermined concentration is reached, which may be indicated by the colloidal dispersion level sensor 12. When the predetermined colloidal dispersion is reached, the ultrafiltration membrane permeable valve 45 is turned off, so that the valve 45 is now closed. In other words, FIG. 4 illustrates the system state that is activated when the concentration of the colloidal dispersion (and therefore the concentration of LSPR particles 35) is at an optimal level to achieve optimal signal strength in the readout from the Raman flow cell 15.

[0032] 3 thus illustrates step (c), previously described, performed by processor 37, i.e., opening permeable valve 45 to divert colloidal dispersion to ultrafiltration membrane 20 so that a predetermined colloidal dispersion level is reached, as indicated by colloidal dispersion level sensor 12. FIG. 4 illustrates the system upon completion of step (c). Note that step (b) should be performed at least once prior to introduction of fluid sample 30 to system 5, but may be performed one or more times or repeatedly during step (c). Thus, system 5 may have one or more baseline readings from Raman spectrometer / flow cell 15 before sample 30 is introduced for analysis.

[0033] After reaching the state in Figure 4, system 5 can proceed to unsteady state analysis (Figure 5) or steady state or in-line analysis (Figure 6). The difference is that in unsteady state analysis, permeable membrane valve 45 remains closed, so the degree of colloidal dispersion circulating in colloidal dispersion circuit 7 does not remain constant as fluid sample 30 is introduced. Unsteady state can be used to test small, finite fluid samples.

[0034] When system 5 is used in-line as part of a larger existing manufacturing system, altered amounts of liquid may affect the accuracy of the Raman spectroscopy / flow cell 15 readout, so steady state analysis may be desired. In the steady state analysis configuration shown in FIG. 6, the ultrafiltration membrane permeate valve 45, and (if present) the reservoir valve 55, are adjusted to allow a portion of the liquid in the colloidal dispersion to exit as permeate liquid 22 and enter the permeate liquid reservoir 25. This adjustment is made so that as the fluid sample 30 to be analyzed enters the reservoir 10, the amount of liquid introduced by the fluid sample valve / injection port 60 into system 5, and more specifically into the colloidal dispersion circulation 7, is approximately the same as the amount of liquid 22 that permeates from the circulation 7, so that the amount of total circulating fluid remains unchanged and the concentration of LSPR particles 35 remains relatively unchanged for a more accurate readout from the Raman spectrometer / flow cell 15.

[0035] In the unsteady state configuration of Figure 5 or the steady state configuration of Figure 6, the processor 37 may perform the steps of (d) opening the fluid sample inlet valve 60 to introduce the fluid sample 30 into the colloidal dispersion circuit 7, (e) reading a second signal from the Raman spectrometer / flow cell 15, the second signal being based on Raman scattering, and (f) determining the presence and / or concentration of a contaminant in the fluid sample 30 based on the first signal (or previous signal(s) obtained before the fluid sample 30 was introduced) and the second signal. During step (f), the processor 37 may be configured to identify an amount or concentration of a contaminant in the fluid sample 30 based on the intensity of the second signal from the flow cell 15.

[0036] System 5 may further include a database connected to one or more processors 37, the database including data associating a plurality of spectra with a plurality of contaminants, and in step (f), processor 37 is further configured to identify the type of contaminant in fluid sample 30 based on the database data. Additionally, when system 5 analyzes fluid sample 30 in the steady state configuration shown in Figure 6, processor 37 adjusts permeable valve 45 to maintain a predetermined colloidal dispersion level, which may be achieved by maintaining a constant amount of circulating fluid, as discussed.

[0037] 7 shows the amount of colloidal dispersion in reservoir 10 (circulated by colloidal dispersion circuit 7) decreasing as the system is operated in the configuration of FIG. 3 to reach a desired predetermined colloidal dispersion level (or a predetermined LSPR particle concentration). Note that the concentration of LSPR particles 35 in the colloidal dispersion increases as the colloidal dispersion decreases. The amount of fluid in the circuit and in reservoir 10 decreases as some of the liquid permeates through ultrafiltration membrane 20 and into permeate reservoir 25.

[0038] It was mentioned above that the fluid contaminant detection system 5 may further include a wash valve 75 configured to introduce a wash fluid from the wash fluid reservoir 70 into the colloidal dispersion circuit 7. FIG. 8 shows a wash configuration for the system 5 to circulate the wash fluid. The wash valve 75 is connected to and operated by the processor 37, which may perform the following steps at some point after step (c): close the fluid sample valve or injection port 60, open the permeate valve 45, and open the wash valve 75. Preferably, the wash fluid may permeate through the ultrafiltration membrane 20 into the permeate reservoir 25. The wash fluid may be introduced into the colloidal dispersion circuit and permeate until the contaminants are removed. This may be determined by taking a readout from the Raman spectrometer / flow cell 15 and continuing the wash process until a baseline Raman signal is reached (i.e., a signal that matches the Raman signal of the system 5 in FIG. 4 is achieved). If the contaminant is adsorbed, the wash solution should be selected to selectively dissolve, complex, oxidize, reduce, or any combination thereof, the contaminant from the LSPR particle surface.

[0039] We now discuss a method for detecting contaminants in a sample 900, shown in FIG. The method includes, at a minimum, (a) introducing (910) a colloidal dispersion of a liquid (905) and colloidal LSPR particles; (b) exposing (915) the colloidal dispersion with electromagnetic radiation sufficient to induce surface-enhanced Raman scattering in the colloidal dispersion of LSPR particles; (c) measuring (920) the scattered electromagnetic radiation from step (b) and storing (925) it as a first measurement; (d) introducing (940) a sample to the colloidal dispersion; (e) exposing (945) the sample / colloidal dispersion mixture with electromagnetic radiation sufficient to induce surface-enhanced Raman scattering in the colloidal dispersion of LSPR particles; (f) measuring (950) the scattered electromagnetic radiation from step (e) and storing (955) it as a second measurement; and (g) determining the presence of a contaminant in the sample by comparing (960) the measurement from step (c) to the measurement from step (f). After step (a), and possibly before step (d), the method may further include concentrating the LSPR particles by permeating (930, 935) liquid through the colloidal dispersion. Although the steps of permeating (930) liquid through the colloidal dispersion and determining if the colloidal dispersion has reached a predetermined colloidal dispersion level (935) are shown as occurring after exposing (915) the colloidal dispersion to radiation and measuring (920) the scattered electromagnetic radiation from the colloidal dispersion, steps (930, 935) may also occur prior to (915, 920) or simultaneously with (915, 920).

[0040] In addition to concentrating the LSPR particles to a predetermined colloidal dispersion level by permeating only liquid from the colloidal dispersion (930, 935), the method can further include permeating the sample / colloidal dispersion mixture to maintain the predetermined colloidal dispersion level (942) during steps (d), (e), and (f), which is similar to the system configuration in FIG.

[0041] Method 900 may further include (h) comparing the measurements from steps (c) and (f) to a database including data associating a plurality of spectra with a plurality of contaminants (963), and (i) identifying the type of contaminant based on the comparison in step (h) (965 in FIG. 9). Method 900 may also include (j) identifying the concentration or amount of the contaminant based on the intensity of the measurements in step (f) (970 in FIG. 9). A further variation of method 900 may include, as part of step 930, as part of step 942, or as part of both steps, selecting a filtration membrane from a plurality of membranes each having pores of different sizes, and thus permeating particles of different sizes, as permeating liquid from the colloidal dispersion. Additionally, method 900 may further include circulating a cleaning liquid to clean the colloidal dispersion circulation path.

[0042] The present invention has been described with respect to certain embodiments that illustrate examples of the invention but do not limit the scope of the invention. Various exemplary systems having various aspects and elements have been shown and described. Unless otherwise indicated, any feature, aspect or element of any of these systems may be removed from, added to, combined with, or modified by any other feature, aspect or element of any of the systems. As would be apparent to one skilled in the art, changes and modifications to the above-described systems and methods may be made without departing from the spirit and scope of the invention, which is defined solely by the appended claims. Moreover, the applicants do not specifically intend that the appended claims and "embodiments in the specification be strictly coextensive" (Phillips v. AHW Corp., 415 F.3d 1303, 1323 (U.S. Court of Appeals for the Federal Circuit, 2005) (En banc)).

Claims

1. 1. A system for detecting a contaminant in a fluid sample, comprising: A colloidal dispersion circulation path, a reservoir containing a colloidal dispersion having localized surface plasmon resonance ("LSPR") particles; A Raman spectrometer / flow cell; a pump for circulating the colloidal dispersion through the colloidal dispersion circulation path; A colloidal dispersion circulation path comprising: a colloidal dispersion level sensor configured to determine a concentration or level of the colloidal dispersion in the colloidal dispersion circuit; a permeable valve configured to redirect the colloidal dispersion in the colloidal dispersion circuit through an ultrafiltration membrane having a pore size smaller than the LSPR particles, thereby preventing the LSPR particles from passing therethrough; a fluid sample injection valve configured to introduce the fluid sample into the colloidal dispersion circuit; a processor coupled to said pump, said Raman spectrometer / flow cell, said transmission valve, said colloidal dispersion level sensor, and said fluid sample injection valve, said processor performing the steps of: a. starting the pump; b. reading a first signal from the Raman spectrometer / flow cell, the signal being based on Raman scattering; c. opening the permeate valve to divert the colloidal dispersion to the ultrafiltration membrane so that a predetermined colloidal dispersion level is reached, as indicated by the colloidal dispersion level sensor; d. opening the fluid sample injection valve, thereby introducing the fluid sample into the colloidal dispersion circuit; e. Reading a second signal from the Raman spectrometer / flow cell, the second signal being based on Raman scattering; f. determining the presence of a contaminant in the fluid sample based on the first signal and the second signal; A processor configured to: A system comprising:

2. 2. The system of claim 1, wherein the colloidal dispersion circuit further comprises a reservoir valve between the reservoir and the Raman spectrometer / flow cell, the reservoir valve being connected to the processor, the processor being further configured to open the reservoir valve during step (b).

3. 10. The system of claim 1, wherein after step (c), the processor adjusts the permeate valve to maintain the predetermined colloidal dispersion level.

4. The system further comprises a wash valve configured to introduce a wash fluid from a wash fluid reservoir into the colloidal dispersion circuit, the wash valve being connected to the processor, and after step (c), the processor: closing the fluid sample injection valve; Open the permeation valve; opening the flush valve; The system of claim 1 .

5. 2. The system of claim 1, further comprising a database connected to the processor, the database including data associating a plurality of spectra with a plurality of contaminants, and in step (f), the processor is further configured to identify a type of contaminant based on data in the database.

6. The system of claim 5 , wherein in step (f), the processor is further configured to determine an amount of contaminant based on a strength of the second signal.

7. 1. A method for detecting a contaminant in a sample, comprising: a. introducing a colloidal dispersion of a liquid and colloidal localized surface plasmon resonance ("LSPR") particles and concentrating the LSPR particles by permeating the liquid through the colloidal dispersion; b. exposing the colloidal dispersion to electromagnetic radiation sufficient to induce surface-enhanced Raman scattering in the LSPR particles; c. Measuring the scattered electromagnetic radiation from step (b); d. introducing the sample into the colloidal dispersion; e. exposing the sample / colloidal dispersion mixture to electromagnetic radiation sufficient to induce surface-enhanced Raman scattering in the colloidal dispersion of LSPR particles; f. Measuring the scattered electromagnetic radiation from step (e); g. determining the presence of contaminants in said sample by comparing the measurements from step (c) with the measurements from step (f); A method comprising:

8. In step (a), the LSPR particles are concentrated to a predetermined colloidal dispersion level; permeating the sample / colloidal dispersion mixture during steps (d), (e) and (f) to maintain the predetermined colloidal dispersion level; The method of claim 7 further comprising:

9. h. comparing the measurements from steps (c) and (f) to a database containing data relating a plurality of spectra to a plurality of contaminants; i. identifying a type of contaminant based on the comparison in step (h).

10. 10. The method of claim 9, further comprising the step of: determining an amount of the contaminant based on the intensity of the measurement in step (f).

11. The method of claim 7, further comprising circulating a cleaning solution to clean the colloidal dispersion circulation path.

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