WO2024011021A1

WO2024011021A1 - Test cell assembly including attenuated total reflector

Info

Publication number: WO2024011021A1
Application number: PCT/US2023/068913
Authority: WO
Inventors: Jeremy Rowlette; H.t. STINSON; William Chapman; Michael Pushkarsky; David Francis Arnone; Edeline Fotheringham; Rudy BERMUDEZ
Original assignee: Daylight Solutions, Inc.
Priority date: 2022-07-08
Filing date: 2023-06-22
Publication date: 2024-01-11

Abstract

A test cell assembly (924) for receiving a sample (12) that is analyzed with an incident light beam (928a) includes a test cell (925). The test cell (925) includes an attenuated total reflector having a curved first surface (925a) that defines at least a portion of a test internal channel (960) for receiving the sample (12), a second surface (925b) that is spaced apart from the first surface (925a), and an access area (925C) for receiving the incident light beam (928a) that is directed at the first surface (925a). The attenuated total reflector can have an annular shape and can be sized and shaped so that the test internal channel (960) corresponds to and matches the size and shape of an inlet conduit (954) that directs the sample (14) to the test cell (925).

Description

TEST CELL ASSEMBLY INCLUDING

ATTENUATED TOTAL REFLECTOR

RELATED APPLICATION

This application is related to U.S. Provisional Application No: 63/359,458, filed on July 8, 2022, and entitled “In-Line Fluid Analyzer System With Reference Measurement.” This application is also related to U.S. Provisional Application No: 63/454,527, filed on March 24, 2023, and entitled “Test Cell Assembly Including Attenuated Total Reflector.” As far as permitted, the contents of U.S. Provisional Application No: 63/359,458, and U.S. Provisional Application No: 63/454,527 are incorporated herein by reference.

BACKGROUND

[0001] It is often necessary to accurately characterize and/or monitor a fluid in an inline, closed process over a lengthy time scale, e.g., hours, days, or weeks. As a nonexclusive example, it is necessary to characterize and monitor a manufactured biopharmaceutical in closed and sterile processes, especially during purification, polishing, and recovery steps which can include liquid chromatographic separations (ion exchange and size exclusion, etc.) and filtration (e.g., ultrafiltration, diafiltration, tangential flow filtration). Unfortunately, existing analyzer systems for in-line monitoring of closed processes are not able to accurately and continuously perform an uninterrupted series of high-sensitivity measurements over lengthy time scales due to sensor drift. SUMMARY

[0002] A test cell assembly for receiving a sample that is analyzed with an incident light beam includes a test cell including an attenuated total reflector having a curved first surface that defines at least a portion of a test internal channel for receiving the sample, a second surface that is spaced apart from the curved first surface, and an access area for receiving the incident light beam that is directed at the first surface.

[0003] In some implementations, the attenuated total reflector is annular-shaped. The attenuated total reflector can be hollow cylindrical shaped, the second surface can be curved, and the second surface can be substantially coaxial with the first surface. The attenuated total reflector can include an arch-shaped region.

[0004] In various implementations, at least one of the surfaces has an index of refraction of greater than approximately 1 .35.

[0005] In certain implementations, the access area is on the second surface, and the incident light beam has an incidence angle on the first surface of between approximately twenty and fifty degrees. The access area can be configured to allow the light beam to exit the attenuated total reflector. The access area can include a first access region and a second access region. The incident light beam can pass through the first access region, and the light beam can exit from the test cell from the second access region. The access area can include at least one of an aperture, a flat, a notch, and a groove.

[0006] In some implementations, the surfaces are configured so that (i) the light beam strikes the curved first surface at an incidence angle greater than a critical angle of the curved first surface, and (ii) the light beam propagates between the surfaces with successive reflections between the curved first surface and the second surface. The light beam can propagate between the curved first surface and the second surface for at least five bounces. The light beam can propagate between the curved first surface and the second surface in one of (i) a clockwise direction, and (ii) a counterclockwise direction relative to a central axis of the test internal channel. The light beam can reflect between the curved first surface and the second surface in a helical manner relative to a central axis of the test internal channel.

[0007] In various implementations, the curved first surface can include a film that includes at least one of the following characteristics (i) improves the chemical stability of the curved first surface, (ii) inhibits binding of biological materials to the curved first surface, (iii) at least partially hydrophilic, and (iv) at least partially hydrophobic.

[0008] An assembly including a test cell assembly, an inlet conduit having an inlet channel that is adapted to receive the sample, the inlet channel having an inlet cross- sectional area and an inlet cross-sectional shape, wherein the test internal channel is in fluid communication with the inlet channel so that the sample moves from the inlet channel to the test internal channel, wherein the test internal channel has a test cross-sectional area that is approximately equal to the inlet cross-sectional area, and a test cross- sectional shape that is approximately equal to the inlet cross-sectional shape. The assembly can include an outlet conduit having an outlet channel that is adapted to receive the sample, the outlet channel having an outlet cross-sectional area, and an outlet cross- sectional shape, wherein the test internal channel is in fluid communication with the outlet channel so that the sample moves from the inlet channel to the test internal channel to the outlet channel, wherein the test cross-sectional area is approximately equal to the outlet cross-sectional area, and the test cross-sectional shape is approximately equal to the outlet cross-sectional shape. The inlet channel can have a circular cross-sectional shape, the outlet channel can have a circular cross-sectional shape, and the test internal channel can have a circular cross-sectional shape.

[0009] In various implementations, the assembly can further include a light source that directs the incident light beam through the access area at the first surface with the light beam having an incidence angle of greater than a critical angle of the test cell. The incident light beam can have a parallel polarization. The incident light beam can be converging. The incident light beam can have a virtual focal point that is located within the test internal channel. The incident light beam can satisfy a 4-f Fourier optical system. [0010] An assembly including a test cell assembly, an inlet conduit that directs the sample to the test cell, and an outlet conduit that receives the sample from the test cell, wherein test cell assembly includes a cell housing that retains the test cell; wherein the cell housing includes (i) a first connector component that selectively couples the cell housing to the inlet conduit with the inlet conduit being in fluid communication with the test cell, and (ii) a second connector component that selectively couples the cell housing to the outlet conduit with the outlet conduit being in fluid communication with the test cell. The test cell can be positioned between the first connector component and the second connector component. The cell housing can include a housing optical access area that is alignable with the access area so that the incident light beam can be directed at the first surface through the cell housing. The cell housing can include a test cell aligner that aligns the test cell with the cell housing.

[0011] In certain implementations, the assembly further includes (i) a detector that receives the light beam from the test cell and generates detector data, and (ii) a control- and-analysis system that uses the detector data to analyze the sample.

[0012] A fluid analyzer for analyzing a sample includes a test cell assembly that receives the sample, the test cell assembly including an attenuated total reflector that contacts the sample, the attenuated total reflector including a first ATR region and a second ATR region that is spaced apart from the first ATR region; a light source assembly that directs a first light beam into the first ATR region that is reflected within the first ATR region; and a second light beam into the second ATR region that is reflected within the second ATR region; a first detector that generates a first data that corresponds to the light reflected within the first ATR region; a second detector that generates a second data that corresponds to the light reflected within the first ATR region; and a control system that uses the first data and the second data to analyze the flowing sample.

[0013] In some implementations, a first beam center wavelength of the first light beam is approximately equal to a second beam center wavelength of the second light beam. The first beam center wavelength can be changed over time as the sample moves in the test cell assembly. The second beam center wavelength can be changed over time as the sample moves in the test cell assembly. The attenuated total reflector can be tubular shaped or trapezoidal shaped.

[0014] A test cell assembly for receiving a sample that is analyzed with an incident light beam includes an inlet conduit having an inlet channel that is adapted to receive the sample, the inlet channel having an inlet cross-sectional area and an inlet cross-sectional shape, and a test cell that defines a test internal channel that is in fluid communication with the inlet channel so that the sample moves from the inlet channel to the test internal channel, the test cell including an attenuated total reflector that contacts the sample, the attenuated total reflector including an access area for receiving the light beam so that the light beam internally reflects within the attenuated total reflector, and wherein the test internal channel has a test cross-sectional area that is approximately equal to the inlet cross-sectional area, and a test cross-sectional shape that is approximately equal to the inlet cross-sectional shape.

[0015] In various implementations, the assembly can further include an outlet conduit having an outlet channel that is adapted to receive the sample that moves from the test internal channel, the outlet channel having an outlet cross-sectional area that is approximately equal to the test cross-sectional area, and an outlet cross-sectional shape that is approximately equal to the test cross-sectional shape.

[0016] In certain implementations, the assembly can include a seal that is configured to seal a junction between the test cell and at least one of the conduits.

[0017] In some implementations, the inlet channel has a circular cross-sectional shape, the outlet channel has a circular cross-sectional shape, and the test internal channel has a circular cross-sectional shape. The inlet channel can have an inlet diameter, the outlet channel can have an outlet diameter, and the test internal channel can have a test diameter. The test diameter can be approximately equal to at least one of the inlet diameter and the outlet diameter.

[0018] A method for analyzing a sample with an incident light beam includes the step of positioning the sample in a test cell including a total attenuated reflector having a curved first surface that defines at least a portion of a test internal channel that receives the sample, a second surface that is spaced apart from the first surface, and an access area for receiving the incident light beam that is reflected within the reflection crystal.

[0019] A fluid analyzer for analyzing a sample includes a test cell assembly that receives the sample, the test cell assembly including an attenuated total reflector that contacts the sample, the attenuated total reflector including a first ATR region and a second ATR region that is spaced apart from the first ATR region; and a light source assembly that directs a first light beam into the first ATR region that is reflected within the first ATR region; and a second light beam into the second ATR region that is reflected within the second ATR region.

[0020] In various implementations, the first ATR region is at least partly positioned in the first test cell and the second ATR region is at least partly positioned in the second test cell. The first ATR region and the second ATR region can be positioned on opposite sides of an ATR central axis of the attenuated total reflector.

[0021] In certain implementations, the fluid analyzer further includes a detector that generates data that corresponds to the light reflected within the ATR regions.

[0022] In some implementations, the attenuated total reflector can include (i) a first reflector surface, (ii) a second reflector surface that is spaced apart from the first reflector surface, (iii) an angled, first end facet for receiving the light beams into the attenuated total reflector, and (iv) an angled, second end facet for allowing the light to exit the attenuated total reflector.

[0023] In various implementations, (i) the first light beam enters through the first end facet and is incident on the second reflector surface in the first ATR region, and (ii) the second light beam enters through the first end facet and is incident on the second reflector surface in the second ATR region.

[0024] In certain implementations, (i) the first light beam reflects between the reflector surfaces in the first ATR region before exiting the second end facet as a first detector beam, and (ii) the second light beam reflects between the reflector surfaces in the second ATR region before exiting the second end facet as a second detector beam. The detector receives the first detector beam and the second detector beam. The first light beam can interrogate the sample in the first ATR region, and the second light beam interrogates the sample in the second ATR region.

[0025] In another implementation, a fluid analyzer for analyzing a flowing sample includes (i) a flow cell assembly that receives the flowing sample, the flow cell assembly having a first location and a second location that is spaced apart from the first location; (ii) a detector assembly that provides a first data that corresponds a characteristic of the sample at the first location, and a second data that corresponds to a characteristic of the sample at the second location; and (iii) a control system that uses the first data and the second data to analyze the flowing sample.

[0026] As an overview, in certain implementations, the fluid analyzer is uniquely designed to continuously and accurately monitor one or more characteristics/properties of the sample in real time, in a closed process, without adversely influencing the sample. Stated in another fashion, the fluid analyzer can be designed to accurately and continuous perform an uninterrupted series of spectroscopic measurements over lengthy time scales. [0027] In one implementation, the detector assembly includes a first detector that generates the first data, and a second detector that generates the second data.

[0028] In one, non-exclusive implementation, the fluid analyzer utilizes a time-domain differential absorption spectroscopy technique with an upstream/downstream signal/reference detection architecture for improved accuracy. Typically, during such a closed process campaign, it is not possible to inject reference fluids into the in-line probe or flow cell of the instrument that would typically be needed to normalize the system, i.e. , create an accurate absorbance measurement. As provided herein, an internal reference fluid standard can be used to perform such a normalization, whereby a light beam is diverted towards a second (reference standard) detector which resides outside of the monitored process. However, it is difficult, if not impossible, to ensure that the reference fluid standard is maintained to the exact same temperature as the background or mobile phase liquid of the process at any given time during the process campaign. Water is commonly used as a background fluid in a bioprocess. The spectral response of water is strongly dependent on temperature. Therefore, an in-line probe or flow-cell having the ability to perform such a background measurement without breaking the closed system is of high value to the industry.

[0029] The detector assembly can include a light source assembly that (i) directs a first beam at the sample flowing in the flow cell assembly in the first location; and (ii) directs a second beam at the sample flowing in the flow cell assembly in the second location. In certain implementations, a first beam center wavelength of the first beam is approximately equal to a second beam center wavelength of the second beam.

[0030] Further, in certain designs, the first beam center wavelength is changed over time as the sample is flowing in the flow cell assembly; and the second beam center wavelength is changed over time as the sample is flowing in the flow cell assembly. In this design, the second beam center wavelength is always equal to the first beam center wavelength even during the changing of the wavelengths.

[0031] As a non-exclusive examples, the first beam center wavelength is changed over time over a desired spectral range, and the second beam center wavelength is changed over time over the desired spectral range. In one implementation, for example, the desired spectral range is at least five, ten, twenty, fifty, eighty, or one hundred percent of a MIR spectral range. It should be noted that the phrase “Mid Infrared” has been abbreviated to be “MIR” for convenience in this application. Further, the phrase “Mid Infrared range” or “MIR range” shall mean and include the spectral region or spectral band of between approximately five thousand to five hundred wavelengths (5000-500 cm^-1), or approximately two and twenty micrometers (2-20 pm) in wavelength.

[0032] In alternative, non-exclusive examples, the desired spectral range can be at least five, ten, twenty, fifty, eighty, or one hundred percent of (i) an ultra-violet spectral range, (ii) a visible light spectral range, (iii) a near infrared spectral range, or (iv) a terahertz spectral range.

[0033] In one implementation, the first beam follows a first optical path from the laser source to the first detector, and the second beam follows a second optical path from the laser source to the second detector; and the first optical path is similar and/or nearly identical to the second optical path.

[0034] As non-exclusive examples, the flow cell assembly can include (i) a transmission cell in which signals are the result of light absorbing in accordance with Beer-Lambert principle; (ii) an attenuated total reflectance cell in which signals are the result of absorption of the light which evanescently couples into the fluid in accordance with Beer-Lambert principle; or (iii) an interface reflectance cell in which signals are the result of changes in the index of refraction between the window and fluid.

[0035] Additionally, the fluid analyzer can include one or more of the following: (i) one or more temperature sensors that sense the temperature of the sample in the flow cell assembly; (ii) one or more conductivity sensors that sense the conductivity of the sample in the flow cell assembly; (iii) one or more pH sensors that sense the pH level of the sample in the flow cell assembly; (iv) one or more flow rate sensor that senses a flow rate of the sample in the flow cell assembly; and/or (v) one or more heat capacity or enthalpy sensors that sense the heat capacity or enthalpy of the sample in the flow cell assembly. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] The novel features of this invention, as well as the invention itself, both as to its structure and its operation, will be best understood from the accompanying drawings, taken in conjunction with the accompanying description, in which similar reference characters refer to similar parts, and in which:

[0037] Figure 1 is a simplified schematic illustration of a processing assembly including a fluid analyzer;

[0038] Figures 2A-2C are simplified illustrations of a portion of the fluid analyzer at different times;

[0039] Figure 2D is a simplified, cut-away illustration of a portion of an implementation of a test cell assembly;

[0040] Figure 3A is a simplified perspective view of a portion of another implementation of the processing assembly;

[0041] Figure 3B is a cut-away view taken on line 3B-3B in Figure 3A;

[0042] Figure 3C is a cut-away view taken on line 3C-3C in Figure 3A;

[0043] Figure 4 is a simplified perspective view of a portion of yet another implementation of the processing assembly;

[0044] Figures 5A-5D are alternative examples that illustrate the reduction in noise that is possible with the fluid analyzer of Figure 1 ;

[0045] Figure 6 is a simplified, cut-away illustration of a portion of another implementation of a processing assembly;

[0046] Figure 7 is a simplified schematic that illustrates the concept that an analyte displaces some mobile phase fluid;

[0047] Figure 8 is a simplified illustration of a portion of another implementation of a processing assembly;

[0048] Figure 9A is a simplified end view of a portion of yet another implementation of a processing assembly;

[0049] Figure 9B is a simplified cut-away view of a test cell from Figure 9A, with an inlet conduit and an outlet conduit;

[0050] Figure 9C is another illustration of the test cell; [0051] Figure 10 is a simplified illustration of still another implementation of a processing assembly;

[0052] Figure 11 is a simplified cut-away illustration of a test cell assembly, an inlet conduit, and an outlet conduit;

[0053] Figure 12 is a simplified cut-away illustration of another implementation of a test cell assembly, an inlet conduit, and an outlet conduit;

[0054] Figure 13 is a simplified side view of yet another implementation of the test cell;

[0055] Figure 14 is a simplified illustration of the test cell and a normally oriented, incident beam;

[0056] Figure 15 is a simplified illustration of the test cell and an incident beam at an angle greater than the critical angle;

[0057] Figure 16 is a simplified illustration of the test cell of Figure 15 with the beam reflecting within the test cell;

[0058] Figure 17 is a simplified illustration of a portion of yet another implementation of a processing assembly;

[0059] Figure 18 is a simplified chart that illustrates possible characteristics of the processing assembly;

[0060] Figure 19A is a simplified cut-away of a portion of still another implementation of a processing assembly;

[0061] Figure 19B is a simplified side view of a portion of the implementation of the processing assembly shown in Figure 19A;

[0062] Figure 19C is a simplified end view of the portion of the implementation of the processing assembly shown in Figure 19B; and

[0063] Figure 20 is a simplified end view of yet another implementation of a processing assembly that is substantially similar to the implementation displayed in Figure 19C.

DESCRIPTION

[0064] Figure 1 is a simplified illustration of a non-exclusive example of a processing assembly 10 that mixes, accurately characterizes, and/or monitors a flowing fluid sample 12 in an in-line, real-time, closed process over a lengthy time scale, e.g., hours, days, or weeks. In the non-exclusive implementation of Figure 1 , the processing assembly 10 includes (i) a sample delivery system 14 that delivers the sample 12; (ii) a fluid analyzer 16 that monitors and characterizes the sample 12; (iii) a retainer receptacle 18; and (iv) a control-and-analysis system 20. It should be noted that the number of components, the design of the components, and/or the positioning of the components in the processing assembly 10 can be different than that illustrated in Figure 1 . For example, the processing assembly 10 can be designed with fewer components than illustrated in Figure 1 .

[0065] As an overview, in certain implementations, the fluid analyzer 16 is uniquely designed to accurately and continuously (or intermittently) monitor one or more characteristics of the sample 12 in real-time, in a closed process, without adversely influencing the sample 12. In one, non-exclusive implementation, the fluid analyzer 16 utilizes a time-domain differential absorption spectroscopy technique that simultaneously acquires a first data signal 21 a (illustrated as a box) over time, and a second data signal 21 b (illustrated as a box) over time of the sample 12 for improved accuracy.

[0066] Further, in certain implementations, the fluid analyzer 16 is uniquely designed to (i) provide for a more stable flow of the sample 12, (ii) provide a more compact configuration, and/or (iii) provide components that can be easily replaced when they become fouled.

[0067] The type of sample 12 that is spectrally analyzed can vary. As non-exclusive examples, the sample 12 can be (i) a fluid, (ii) a complex mixture of multiple liquids, or (iii) a complex mixture of liquids, dissolved chemicals, solvents, and/or solids. In certain embodiments, the sample 12 is a complex mixture that includes one or more different constituents (also referred to as “components”). In one implementation, the sample 12 is a complex mixture that includes one or more analytes 12A (illustrated with small circles) and a mobile phase fluid 12B (illustrated with small squares). As non-exclusive examples, (i) the analytes 12A can include biopharmaceuticals such as small molecules, manufactured proteins (e.g., monoclonal antibodies, bispecific antibodies, fusion proteins, antibody-drug conjugates, antibody saccharide conjugates, etc.), empty, partial or full viral particles or capsids (e.g., adenovirus, adeno associated virus, or lentivirus, etc.), peptides, small molecules, protein-small-molecule conjugates, lipid nanoparticles, amino acids, nucleic acids, oligopeptides, oligonucleotides, RNA, DNA, mRNA, etc.; and/or (ii) the mobile phase fluid 12B can be aqueous, organic or inorganic, including pure water, phosphate-buffered saline (PBS) buffer solution, sodium acetate, dimethyl sulfoxide (DMSO), isopropyl alcohol, methyl alcohol, toluene, tetrahydrofuran (THF), or another type of buffer solution. The term “sample” 12, as used herein, can refer to the analyte 12A, the mobile phase fluid 12B, and/or the mixture of the mobile phase fluid 12B and the analyte 12A.

[0068] The sample delivery system 14 delivers the sample 12 to the fluid analyzer 16 for analysis. The design of the sample delivery system 14 can be varied according to the type of sample 12. In the non-exclusive implementation of Figure 1 , the sample delivery system 14 includes an analyte receptacle 14A that retains the analyte 12A, a mobile phase receptacle 14B that retains the mobile phase fluid 12B, and a mixer 14C that accurately mixes the analyte 12A with the mobile phase fluid 12B. Alternatively, the sample delivery system 14 can have another design.

[0069] It should be noted that the sample delivery system 14 can include one or more pumps (not shown) that move the fluid, one or more filters (not shown), one or more temperature controllers (not shown) that control the temperature of the fluid, and/or one or more pressure sensors (not shown).

[0070] Moreover, the sample delivery system 14 can include an inlet conduit 54 that transports the sample 12 to the fluid analyzer 16. For example, the inlet conduit 54 can include a flexible tube, cylindrical tubing, or any other suitable conduit.

[0071] As provided herein, the flow 22 (illustrated with an arrow) of the sample 12 through the fluid analyzer 16 can be substantially constant or variable. As alternative, non-exclusive examples, the sample delivery system 14 can direct the sample 12 at a substantially constant flow rate of approximately 0.1 mL/min, 0.2 mL/min, 0.5 mL/min, 0.7 mL/min, 1.0 mL/min, 2.0 mL/min, 5.0 mL/min, 10.0 mL/min, 15 mL/min, 20 mL/min, 25 mL/min, 50 mL/min, 100 mL/min, 200 mL/min, 300 mL/min, 500 mL/min, 1000 mL/min, 3000 mL/min, 5000 mL/min or 10,000 mL/min through the fluid analyzer 16 depending on the scale of the process.

[0072] As provided above, the fluid analyzer 16 can continuously or intermittently, accurately monitor the sample 12 in real-time, in a closed process, without adversely influencing the sample 12. A number of alternative, non-exclusive implementations of the fluid analyzer 16 are disclosed herein. [0073] In the non-exclusive implementation illustrated in Figure 1 , the fluid analyzer 16 utilizes a time-domain differential absorption spectroscopy technique which simultaneously acquires first data 21a (illustrated as a box) on a first detector path, and second data 21 b (illustrated as a box) on a second detector path. It should be noted that the first data 21 a can be referred to as signal data, and/or the second data 21 b, can be referred to as reference data. Further, the first detector path can be referred to as a “signal path,” and the second detector path can be referred to as a “reference path.” [0074] In Figure 1 , the fluid analyzer 16 includes a test cell assembly 24, and a detector assembly 26. The design of each of these assemblies can be varied to vary the characteristics of the fluid analyzer 16.

[0075] The test cell assembly 24 receives the sample 12 during analysis with the detector assembly 26. The test cell assembly 24 can alternatively be referred to as a flow cell assembly for implementations with a flowing sample 12. In the simplified example of Figure 1 , the test cell assembly 24 is illustrated as a straight tube that includes a first location 24a and a spaced-apart second location 24b. Alternatively, for example, the test cell assembly 24 can be designed and arranged so that the first location 24a and the second location 24b are side-by-side or in another configuration.

[0076] In the design of Figure 1 , the first location 24a is upstream of the second location 24b. Stated in another fashion, the second location 24b is downstream of the first location 24a. The amount of separation distance 24c between the first location 24a and the second location 24b can be varied in accordance with the update rate of the fluid analyzer 16 and the linear velocity of the sample 12, which is proportional to the ratio of the volumetric flow rate (mL/min) and the cross-sectional area of the inner walls of the test cell assembly (e.g., a tube) carrying the flowing sample 12. In Figure 1 , the separation distance 24c is illustrated as being not very large for convenience of illustration.

[0077] In certain implementations, the separation distance 24c is greater than or equal to the product of a fluid velocity of the flowing sample 12 and a measurement sampling time of the detector assembly 26. As non-exclusive examples, the separation distance 24c can be approximately 0.1 , 0.5, 1 , 5, 10, 15, 20, 25, 35, 50, or 100 centimeters. As one non-exclusive embodiment, a fluid analyzer 16 having an update rate of 10 Hz (0.1 sec between detector sample collection), a separation distance of at least 18.5 cm (or 7.29 inches) between the first and second locations 24a, 24b will be required to accurately measure a process stream having a 3000 mL/min volumetric flow rate and an inner tube diameter of 6 millimeters for the test cell assembly 24.

[0078] It should be noted that the separation distance 24c and/or the volumetric flow rate of the sample 12 in the test cell assembly 24 can be varied to achieve the desired time-domain separation between the first data 21 a that is acquired from the first location 24a, and the second data 21 b that is acquired from the second location 24b. For a particular design that is used at volumetric flow rates substantially below the maximum volumetric flow rate limit of the test cell assembly 24 (determined by the separation distance and the maximum fluid velocity), accumulation and averaging of data samples can be performed to reduce the effective update rate of the fluid analyzer 16.

[0079] In certain embodiments, the test cell assembly 24 can be designed to preserve the quality of the sample 12 as it moves through the test cell assembly 24, for example, by avoiding turbulent flow and minimizing temperature gradients across the test cell assembly 24.

[0080] Further, in certain, non-exclusive implementations, the test cell assembly 24 has a first sample path length 24d across the test cell assembly 24 at the first location 24a, and a second sample path length 24e across the test cell assembly 24 at the second location 24b. In Figure 1 , the first sample path length 24d is approximately equal to (or “approximately the same as”) the second sample path length 24e. As used herein, as alternative, non-exclusive examples, the sample path lengths 24d, 24e are “approximately equal” or “approximately the same” if they are within 0.1 , 0.5, 1 , 5, or 10 percent of each other. As non-exclusive implementations, the sample path lengths 24d, 24e are less than approximately one, two, five, ten, twenty, twenty-five, thirty, fifty, seventy-five, one hundred, one hundred and fifty, two hundred, five hundred, seven hundred, one thousand, two thousand, five thousand, or ten thousand micrometers (1 , 2, 5, 10, 20, 25, 30, 50, 75, 100, 150, 200, 500, 700, 1000, 2000, 5000, 10000 pm). Alternatively, the sample path lengths 24d, 24e can be different from each other, and the control-and-analysis system 20 can account for these different sample path lengths 24d, 24e. [0081] In one implementation, the detector assembly 26 substantially simultaneously captures the data 21a, 21b at approximately the same wavelength (or set of wavelengths) at the two spaced apart locations 24a, 24b. Subsequently, that data 21 a, 21 b is used by the control-and-analysis system 20 to spectrally analyze the sample 12. With this implementation, the detector assembly 26 uses time-domain differential absorption spectroscopy to spectrally analyze the sample 12.

[0082] In one implementation, the detector assembly 26 spectrally analyzes the sample 12 in the MIR range. Alternatively, the detector assembly 26 can spectrally analyze the sample 12 in a different spectral range. For example, the detector assembly 26 can spectrally analyze the sample in the ultra-violet spectral range, the visible spectral range, the near-infrared spectral range, or the terahertz spectral range. Still alternatively, for example, the detector assembly 26 utilizes light scattering instead of spectroscopy.

[0083] In the simplified, non-exclusive implementation of Figure 1 , the detector assembly 26 includes a light source assembly 28, a first detector 30, and a second detector 32 that is spaced apart from the first detector 30. The design of each of these components can be varied.

[0084] The light source assembly 28 generates one or more light beams 28a, 28B that are used to spectrally analyze the sample 12 at the first location 24a and the second location 24b. In Figure 1 , the light source assembly 28 directs a first light beam 28a at the first location 24a, and a second light beam 28b at the second location 24b, at approximately the same wavelength, and at approximately the same time. As alternative examples, as used herein, “approximately the same wavelength” shall mean that the light beams 28a, 28b within 0.01 , 0.05, 0.1 , 0.5, or 1 .0 percent of each other. As alternative examples, as used herein, “approximately the same time” shall mean within 10, 100, 500, 1000, 5000, and 10000 nanoseconds of each other.

[0085] In the non-exclusive implementation of Figure 1 , the light source assembly 28 includes a laser source 34, a beam splitter 36, and a beam director assembly 38 that cooperate to direct the first light beam 28a at the first location 24a, and the second light beam 28b at the second location 24b.

[0086] For example, the laser source 34 can generate a collimated source light beam 40 that is directed at the beam splitter 36 to provide the first light beam 28a and the second light beam 28b. In one implementation, the first light beam 28a is converging at the first location 24a on the test cell assembly 24, and the second light beam 28b is converging at the second location 24b on the test cell assembly 24. In one implementation, the laser source 34 is a tunable laser that can be rapidly tuned over the desired spectral range. In a specific implementation, the laser source 34 is a tunable MIR laser that can be rapidly tuned over a portion or the entire MIR spectral range. With this design, the laser source 34 directly generates and emits the substantially temporally coherent source laser beam 40 that has a center wavelength that is tunable in the MIR range. Alternatively, the laser source 34 can be a fixed wavelength source that is not tunable.

[0087] In Figure 1 , the laser source 34 can have an external cavity, Littrow configuration, and can directly generate the source laser beam 40. As alternative, nonexclusive examples, the laser source 34 is designed so that the source laser beam 40 has an optical power of at least one, ten, twenty, fifty, or one hundred milli-Watts.

[0088] As a non-exclusive implementation, the laser source 34 can include (i) a gain medium 34a (e.g., a Quantum Cascade gain medium); (ii) a wavelength selective feedback element 34b (e.g., a diffraction grating and an actuator that rapidly moves the grating) that can be rapidly adjusted to rapidly select (tune) the center wavelength of the source laser beam 40 in a closed loop fashion; (iii) an intra-cavity lens assembly 34c; and (iv) an output lens assembly 34d. For example, the intra-cavity lens assembly 34c and/or the output lens assembly 34d can each include one or more lenses made of materials that are operable in the mid-infrared range.

[0089] With this design, the control-and-analysis system 20 can control the current to the gain medium 34a and the position of the wavelength selective feedback element 34b to control the center wavelength of the source laser beam 40 and rapidly modulate the center wavelength of the source laser beam 40.

[0090] The quantum cascade gain medium 34a can provide a tightly focused source laser beam 40 (e.g., less than 0.1 centimeters) so that relatively small (e.g., less than 0.5, 1.0, 1.5, or 2.0 millimeter) transmission windows can be used in the test cell assembly 24. [0091] Alternatively, or additionally, the light source assembly 28 can include one or more of (i) an ultra-violet light source, (ii) a visible light source, (iii) a near-infrared light source, and (iv) a terahertz light source. It should be noted that the light source assembly 28 can include a coherent light source and/or an incoherent light source.

[0092] The beam splitter 36 splits the source light beam 40 into the first light beam 28a and the second light beam 28b. With this design, in certain implementations, the light beams 28a, 28b have exactly the same center wavelength at the same time.

[0093] The beam director assembly 38 directs the first light beam 28a to the first location 24a and the second light beam 28b to the second location 24b. For example, the beam director assembly 38 can include one or more turning mirrors 38a.

[0094] In certain embodiments, the beam splitter 36 and the beam director assembly 38 are designed so that a first optical path of the first light beam 28a from the beam splitter 36 to the first detector 30 is approximately equal to (or “approximately the same as”) a second optical path of the second light beam 28b from the beam splitter 36 to the second detector 32.

[0095] The design of each detector 30, 32 can be varied to suit the wavelength(s) of the light beams 28a, 28b. As non-exclusive examples, each detector 30, 32 can be a single element point detector or a two-dimensional array of sensors, such as a thermoelectrically cooled, photoconductive, InAsSb (indium arsenide antimonide) detector. Alternatively, another type of detector 30, 32 can be utilized.

[0096] The first detector 30 generates the first data 21 a that corresponds to a composition/characteristic of the sample 12 at the first location 24, and the second detector 32 generates the second data 21 b that corresponds to a composition/characteristic of the sample 12 at the second location 24b. The first data 21a can be referred to as “upstream data” or “signal data,” and/or the second data 21 b can be referred to as the “downstream data” or “reference data.”

[0097] With a spectroscopic design, the detectors 30, 32 simultaneously measure the amplitude of light collected as a function wavelength at the two locations 24a, 24b. Further, the absorbance of the sample 12 at the locations 24a, 24b will influence the amplitude of light collected. Stated in another fashion, with the design of Figure 1 , the fluid analyzer 16 effectively defines a pair of spectral analyzers (e.g., MIR spectral analyzers) in series that each generate separate data. However, the fluid analyzer 16 can be designed to define more than two spectral analyzers.

[0098] In Figure 1 , (i) the first light beam 28a directed at the test cell assembly 24 at the first location 24a is transmitted through the test cell assembly 24 and the sample 12, and is collected by the first detector 30; and (ii) the second light beam 28b directed at the test cell assembly 24 at the second location 24b is transmitted through the test cell assembly 24 and the sample 12, and is collected by the second detector 32. For ease of discussion, (i) the first light beam 28a and the first detector 30 can be referred to as a “first detection arm” or “signal detection arm”; and (ii) the second light beam 28b and the second detector 32 can be referred to as a “second detection arm,” or “reference detection arm.”

[0099] In certain designs, the optical path of the signal detection arm and the optical path of the reference detection arm are highly matched (identical) by design in order to ensure high common-mode rejection of laser intensity noise, optical material property drift (e.g., etalons), and effects of scan-to-scan wavelength errors.

[00100] Moreover, in the implementations where the source laser beam 40 is split into the first light beam 28a, and the second light beam 28b, both the sample and reference test paths will have the same noise (and drift) in the beams 28a, 28b, and this can be canceled out.

[00101] With this design, the detector assembly 26 spectrally analyzes the sample 12 at the two, spaced apart locations 24a, 24b, at approximately the same time and approximately the same wavelength (or wavelengths). Furthermore, it is advantageous to have both the upstream (sample) and downstream (reference) fluid sampling locations to be in close proximity despite their fluidic separation distance being relatively large in order to ensure the near isothermal condition of the sample 12 at both points.

[00102] Additionally and optionally, the fluid analyzer 16 can be designed to include one or more of (i) one or more distributed temperature sensors 42 (illustrated as a box) that senses the temperature of the sample 12 in the test cell assembly 24; (ii) a conductivity sensor 44 (illustrated as a box) that senses the conductivity of the sample 12 in the test cell assembly 24; (iii) a pH sensor 46 (illustrated as a box) (e.g., a pH meter) that senses the pH level of the sample 12 in the test cell assembly 24; (iv) a flow rate sensor 48 (illustrated as a box) that senses a flow rate of the sample 12 in the test cell assembly 24; (v) a heat capacity sensor 50 (illustrated as a box) (e.g., a calorimeter) that senses a heat capacity of the sample 12 in the test cell assembly 23; and/or (vi) another type of sensor (not shown).

[00103] The retainer receptacle 18 is in fluid communication with and receives the sample 12 that has been analyzed by the fluid analyzer 16. For example, the retainer receptacle 18 can include one or more containers.

[00104] Moreover, the retainer receptacle 18 can include an outlet conduit 56 that transports the sample 12 from the fluid analyzer 16 to containers. For example, the outlet conduit 56 can include a flexible fluid tube, cylindrical tubing, or any other suitable conduit. [00105] The control-and-analysis system 20 controls one or more components of the processing assembly 10. For example, the control-and-analysis system 20 can control the operation of the sample delivery system 14 and the fluid analyzer 16. Moreover, the control-and-analysis system 20 can analyze the data 21a, 21b generated by the fluid analyzer 16 to characterize one or more components of the sample 12. More specifically, the control-and-analysis system 20 can use the first data 21 a and the second data 21b to spectrally analyze the flowing sample 12.

[00106] In certain embodiments, the control-and-analysis system 20 can utilize the data 21a, 21 b to estimate one or more of (i) the shape of the analyte 12A; (ii) the chemical structure of the analyte 12A; (iii) if the analyte 12A is starting to cluster, bind or aggregate; (iv) a concentration of the sample 12; (v) a concentration of the analyte 12A; and/or (vi) another characteristic of the analyte 12A and/or sample 12. Additionally, the control-and- analysis system 20 can utilize the information from one or more of (i) the temperature sensors 42; (ii) the conductivity sensor 44; (iii) the pH sensor 46; (iv) the flow rate sensor 48; and/or (v) the heat capacity sensor 50 in the analysis of the sample 12.

[00107] In certain embodiments, the control-and-analysis system 20 can include one or more processors 20A and/or electronic data storage devices 20B. It should be noted that the control-and-analysis system 20 is illustrated in Figure 1 as a single, central processing system. Alternatively, the control-and-analysis system 20 can be a distributed processing system. Additionally, the control-and-analysis system 20 can include a display (e.g., LED display) that displays the test results. [00108] With the present design, the fluid analyzer 16 can monitor the sample 12 inline, at various stages, intermittently or constantly, and without adversely influencing the sample 12.

[00109] As provided herein, in certain implementations, the mobile phase fluid 12A is highly absorbing in regions of interest (e.g., the interrogation wavelengths). With the present design, the sets of data 21a, 21 b are acquired simultaneously, at corresponding wavelengths, at different locations, and can be used to reference the absorbance of the mobile phase fluid 12A to improve the accuracy of the measurements.

[00110] Figure 1 illustrates the processing assembly 10 at the beginning of a monitoring process at time one (“T1”). At this time, the mobile phase fluid 12B was first delivered to test cell assembly 24, and subsequently, the mixture of the mobile phase fluid 12B and the analyte 12A is directed to the test cell assembly 24. As illustrated in Figure 1 , as a result thereof, at T1 , (i) the first detection arm generates the first data 21a that corresponds to the absorbance of the mixture of the mobile phase fluid 12B and the analyte 12A, and (ii) the second detection arm generates the second data 21 b that corresponds to the absorbance of just the mobile phase fluid 12B. The difference between the first data 21a and the second data 21 b at this time can be referred to as a “differential signal.” This differential signal represents the difference in absorption at the two, spaced apart locations 24a, 24b.

[00111] With this design, the present invention provides an accurate, real-time, and extremely low-drift time differential signal without the need for removing and separately testing the mobile phase fluid 12B. The desired native signal can then be easily recovered by integrating the differential signal from a suitable start time before or after the start of the process.

[00112] It should be noted that around T1 , the center wavelength of light beams 28a, 28b can be rapidly tuned (i) over a portion (e.g., 5, 10, 20, 30, 40, 50, 60, 70, 80, or 90 percent or more) of the MIR range, the ultra-violet spectral range, the visible spectral range, the near-infrared spectral range, or the terahertz spectral range; (ii) over the entire MIR range, the ultra-violet spectral range, the visible spectral range, the near-infrared spectral range, or the terahertz spectral range; or (iii) to discrete wavelengths of interest to interrogate the analyte 12A and the mobile phase fluid 12B. [00113] Figure 2A is an enlarged, simplified illustration of a portion of the fluid analyzer 16, including a portion of the test cell assembly 24 and the detector assembly 26 at a different, later time (“T2”). At this time, the mixture sample 12 of the mobile phase fluid 12B and the analyte 12A is positioned between and analyzed by both the first detection arm with the first detector 30, and the second detection arm with the second detector 32. As a result, the first data 21a should be approximately equal to the second data 21 b.

[00114] Figure 2B is a simplified illustration of a portion of the fluid analyzer 16 including a portion of the test cell assembly 24 and the detector assembly 26 at still another, different, later time (“T3”). At this time, the analyte 12a is beginning to clump together. The clumping analyte is identified with reference 12C. As illustrated in Figure 2B, as a result thereof, at T3, (i) the first detection arm generates the first data 21a that corresponds to the absorbance of the sample 12 with the clumping analyte 12C, and (ii) the second detection arm generates the second data 21 b that corresponds to the absorbance of sample 12 with the analyte 12A and the mobile phase fluid 12B. The difference between the first data 21 a and the second data 21 b at this time can be used to indicate (identify) clumping and or another characteristic. It should be noted that slightly later in time, the second detection arm will analyze the clumping analyte 12C.

[00115] Figure 2C is a simplified illustration of a portion of the fluid analyzer 16 including a portion of the test cell assembly 24 and the detector assembly 26 at another, later time (“T4”). Just prior to T4, the analyte 12A was no longer added to the sample 12. As illustrated in Figure 2C, as a result thereof, at T4, (i) the first detector 30 of the first detection arm generates the first data 21 a that corresponds to the absorbance of just the mobile phase fluid 12B, and (ii) the second detector 32 of the second detection arm generates the second data 21 b that corresponds to the absorbance mixture of the mobile phase fluid 12B and the analyte 12A. The difference between the first data 21 a and the second data 21 b at this time is the “differential signal.”

[00116] With the present design, the control-and-analysis system 20 can continuously monitor the data 21 a, 21 b to spectrally analyze the sample 12, in-line, without adversely influencing the sample 12. [00117] In certain implementations, minimizing temperature gradients between reference and signal paths is desirable through mixing high-diffusivity and low- conductance materials, etc.

[00118] In certain designs, the spectral response of the mobile phase fluid 12B is strongly dependent on temperature. The present, in-line design provides a background measurement without breaking into the closed system.

[00119] Figure 2D is a simplified, enlarged, cut-away illustration of an implementation of the test cell assembly 24 that can be used in the processing assembly 10 of Figure 1 to analyze the sample 12. The first light beam 28a and the second light beam 28b are also illustrated in Figure 2D. Moreover, a portion of the inlet conduit 54 and the outlet conduit 56 are also shown in Figure 2D.

[00120] In one implementation, the test cell assembly 24 is a transmission-style flow cell that includes (i) a first test cell 25a that defines the first location 24a; (ii) a second test cell 25b that is spaced apart from the first test cell 25a and that defines the second location 24b; and (iii) a connector conduit 52 that connects the test cells 25a, 25b together in fluid communication. In this design, the length of the connector conduit 52 can be selected to adjust the separation distance 24c and achieve the desired time-domain separation between the first data 21a (illustrated in Figure 1 ) and the second data 21 b (illustrated in Figure 1 ).

[00121] In Figure 2D, (i) the first test cell 25a is a transmissive type flow cell that includes a first inlet window 24g and a first outlet widow 24h, and (ii) the second test cell 25b is a transmissive type flow cell that includes a second inlet window 24i, and a second outlet window 24j. Each window 24g-24j is transparent to the wavelength of the respective light beams 28a, 28b. Further, (i) the first inlet window 24g and the first outlet widow 24h are spaced the first sample path length 24d at the first location 24a; and (ii) the second inlet window 24i and the second outlet widow 24j are spaced the second sample path length 24e at the first location 24b. With this design, (i) the first light beam 28a travels through the sample 12, the first sample path length 24d, and exits the first flow cell 25a as a first detector beam 26a that is received by the first detector 30 (illustrated in Figure 1 ); and (ii) the second light beam 28b travels through the sample 12 and the second sample path length 24e, and exits the second flow cell 25b as a first detector beam 26b that is received by the second detector 32 (illustrated in Figure 1 ).

[001221 In the simplified illustration of Figure 2D, the test cells 25a, 25b are illustrated as being substantially coaxial. However, the test cells 25a, 25b can be positioned at other relative positions. For example, the connector conduit 52 can be a flexible tube, and the test cells 25a, 25b can be positioned to be parallel to each other or traverse to each other. [00123] Figure 3A is a simplified, top perspective view of a portion of another implementation of the processing assembly 310, including (i) a test cell assembly 324; (ii) a light source assembly 328 (illustrated as a box) that directs a first light beam 328a (illustrated as an arrow) and a second light beam 328b (illustrated as an arrow) at the test cell assembly 324; (iii) a first detector 330 that receives a first detector beam 326a (illustrated as an arrow) from the test cell assembly 324 and creates the upstream “signal” data; and (iv) a second detector 332 that receives a second detector beam 326b from the test cell assembly 324 and creates the downstream, “reference” data. It should be noted that the light source assembly 328 and the detectors 326a, 326b can be somewhat similar to the corresponding components described above in reference to Figure 1.

[00124] Additionally, it should be noted that the processing assembly 310 can also be designed to include a sample delivery system 14 (illustrated in Figure 1 ), a retainer receptacle 18 (illustrated in Figure 1 ), and/or a control-and-analysis system 20 (illustrated in Figure 1 ) that are somewhat similar to the corresponding components described above. Further, Figure 3A also illustrates a portion of an inlet conduit 354 that connects the sample deliver system 14 to the test cell assembly 324; and a portion of an outlet conduit 356 that connects the test cell assembly 324 to the retainer receptacle 18.

[00125] In Figure 3A, the test cell assembly 324 includes a cell housing 357, a housing divider 358 (illustrated in phantom), an attenuated total reflector (“ATR”) 359 (partially in phantom), and a connector conduit 352 (in partial cut-away and dashed line). The size, shape, and design of these components can be varied to achieve the desired characteristic of the test cell assembly 324. In the non-exclusive design of Figure 3A, the cell housing 357, the housing divider 358, and the attenuated total reflector 359 cooperate to define (i) a first test cell 325a (illustrated in phantom); and (ii) a second test cell 325b (illustrated in phantom) that is separated from the first test cell 325a with the divider 358. As a result, (i) the test cells 325a, 325b are positioned in a compact, a side-by-side format; and (ii) the relative positions of the test cells 325a, 325b are maintained.

[001261 As provided herein, the attenuated total reflector can have a variety of three- dimensional shapes and two-dimensional cross-sectional shapes. In the case of a trapezoidal shape, the light may experience at least one but often a series of reflections, bouncing back and forth from one side of the attenuated total reflector to the other while advancing down the long orientation of the attenuated total reflector in the direction of flow or opposite to (against) the direction of flow.

[00127] In Figure 3A, (i) the connector conduit 352 can be a flexible conduit; (ii) the two ends of the connector conduit 352 are illustrated; and (iii) a long-dashed line represents the rest of the connector conduit 352. Further, in this design, (i) the connector conduit 352 connects the test cells 325a, 325b together in fluid communication; and (ii) the length of the connector conduit 352 can be selected to provide the desired separation distance 24c (illustrated in Figure 1 ) and achieve the desired time-domain separation between the first data 21 a (illustrated in Figure 1), and the second data 21 b (illustrated in Figure 1 ).

[00128] Optionally, the effective length of the connector conduit 352 can be selectively adjustable to selectively adjust the separation distance 24c. For example, connector conduit 352 can include one or more distance adjusters 352a (illustrated as a box) that can be controlled to selectively adjust the separation distance 24c. Non-exclusive examples of suitable distance adjusters 352a include one or more valves (not shown), and/or telescoping, sliding tubes (not shown). In this design, for example, the separation distance 24c can be adjusted manually through a fluidic slider or automatically via software/electronic control.

[00129] In Figure 3A, (i) the flow of the sample in the first test cell 325a is represented with the dark arrow 312a; and (ii) the flow of the sample in the second test cell 325b is represented with the hollow arrow 312b. In this design, the flow of the sample 312a in the first test cell 325a is in the same direction as the flow of the sample 312b in the second test cell 325b. Alternatively, the test cell assembly 324 can be designed so that the flows 312a, 312b are in opposite directions.

[00130] In the non-exclusive implementation of Figure 3A, the cell housing 357 is generally rectangular box-shaped, defines a housing chamber, and includes (i) a rectangular, housing top 357a; (ii) a rectangular, housing bottom 357b (illustrated in Figure 3C) that is spaced apart from and parallel to the housing top 357a; (iii) a rectangular, housing first side 357c; (iv) a rectangular, housing second side 357d (illustrated in Figure 3B) that is spaced apart from and parallel to the housing first side 357c; (v) a rectangular, housing third side 357e; and (vi) a rectangular, housing fourth side 357f (illustrated in Figure 3B) that is spaced apart from and parallel to the housing third side 357e.

[00131] The housing divider 358 divides the housing chamber of the cell housing 357 into two substantially equal chambers, with each chamber defining one of the test cells 325a, 325b. In this design, the housing divider 358 (i) is substantially parallel to, and positioned half-way between the housing first and second sides 357c, 357d; and (ii) extends between the housing top, bottom, third, and four sides 357a, 357b, 357e, 357f. Alternatively, for example, the housing divider 358 can be designed so that the test cells 325a, 325b are not equally sized.

[00132] The attenuated total reflector 359 provides a structure for spectrally analyzing the sample 312a in the first test cell 325a, and the sample 312b in the second test cell 325b. In Figure 3A, the attenuated total reflector 359 is a one-piece, generally rectangular plate-shaped, and is positioned at least partly within the first test cell 325a, and the second test cell 325b. In this design, the attenuated total reflector 359 extends transversely through the housing third and four sides 357e, 357f, and the housing divider 358. In one, non-exclusive implementation, the attenuated total reflector 359 (i) extends through the middle of the housing divider 358, and the third and fourth sides 357a, 357b, 357e, 357f; and (ii) can be positioned approximately parallel to and half-way between the top and bottom sides 357a, 357b. However, other configurations are possible.

[00133] It should be noted that because the same attenuated total reflector 359 is common to both test cells 325a, 325b, any temperature changes to the attenuated total reflector 359 will influence both test paths simultaneously and can be canceled out. Stated in another fashion, the same attenuated total reflector 359 is shared between the signal path and reference path in order to minimize thermal differences between the two measurement arms. [00134] In the non-exclusive implementation of Figure 3A, the attenuated total reflector 359 includes (i) a first ATR region 359a that is at least partly positioned in the first test cell 325a; and (ii) a second ATR region 359b that is at least partly positioned in the second test cell 325b. Further, the first ATR region 359a and the second ATR region 359b can be positioned on opposite sides of an ATR central axis 359c of the attenuated total reflector 359. Moreover, the attenuated total reflector 359 can include (i) a first reflector surface 359d; (ii) a second reflector surface 359e (illustrated in Figure 3C) that is spaced apart from the first reflector surface 359d; (iii) an angled, first end facet 359f for receiving the light beams 28a, 28b into the attenuated total reflector 359; and (iv) an angled, second end facet 359g for allowing the detector beams 26a, 26b to exit the attenuated total reflector 359. However, other designs are possible. For example, the attenuated total reflector 359 can be a two-piece structure, with one piece defining the first ATR region 359a, and the other piece defining the second ATR region 359b.

[00135] In Figure 3A, (i) the first light beam 28a enters through the first end facet 359f and is incident on the second reflector surface 359e in the first ATR region 359a; (ii) the second light beam 28b enters through the first end facet 359f and is incident on the second reflector surface 359e in the second ATR region 359b; (iii) the first light beam 28a reflects (bounces) one or more times between the reflector surfaces 359d, 359e in the first ATR region 359a before exiting the second end facet 359g; and (iv) the second light beam 28b reflects (bounces) one or more times between the reflector surfaces 359d, 359e in the second ATR region 359b before exiting the second end facet 359g. With this design, the first light beam 328a interrogates the sample 312 at the first location, namely the first ATR region 359a; and the second light beam 324b that interrogates the sample 312 at the second location, namely the second ATR region 359b.

[00136] The type of material used for attenuated total reflector 359 can be varied to suit the wavelengths of the light beam 328a, 328b. Suitable materials can include crystals made of germanium, Thallium halides, zinc selenide, silicon, diamond, Alpha-A^Os, ZrO2, ZnSe, KRS-5, AMTIR, or CdTe. These non-limiting, non-exclusive examples can have varying indices of refraction. Further, the material can be selected to achieve the design requirements of the processing assembly 910. [00137] In Figure 3A, (i) the first test cell 325a includes a first cell inlet 325ai (illustrated in phantom) that is in fluid communication with the sample delivery system 14 via the inlet conduit 354, and a first cell outlet 325ao (illustrated in phantom) that is in fluid communication with the connector conduit 352; and (ii) the second test cell 325b includes a second cell inlet 325bi (illustrated in phantom) that is in fluid communication with the first cell outlet 325ao via the connector conduit 352, and a second cell outlet 325bo (illustrated in phantom) that is in fluid communication with the retainer receptacle 18 via the outlet conduit 356. With this design, the sample 12 sequentially flows (i) from the sample delivery system 14 to the first test cell 325a via the inlet conduit 354; (ii) through the first test cell 325a; (iii) from the first test cell 325a to the second test cell 325b via the connector conduit 352; (iv) through the second test cell 325b; and (v) from the second test cell 325b to the retainer receptacle 18 via the outlet conduit 356.

[00138] Figure 3B is a cut-away view taken on line 3B-3B in Figure 3A. Figure 3B illustrates the test cell assembly 324 forms the first test cell 325a and the second test cell 325b, and includes (i) the housing bottom 357b, the housing first side 357c, the housing second side 357d, the housing third side 357e, and the housing fourth side 357f; (ii) the housing divider 358; and (iii) the attenuated total reflector 359. In this design, (i) the ATR regions 359a, 359b are positioned on opposite sides of the housing divider 358 and the ATR central axis 359c; (ii) the flowing sample 312a in the first test cell 325a flows over the first ATR region 359a; and (iii) the flowing sample 312b in the second test cell 325b flows over the second ATR region 359b.

[00139] Figure 3B also illustrates (i) the inlet conduit 354 is connected to the first cell inlet 325ai; (ii) the connector conduit 352 connects the first cell outlet 325ao to the second cell inlet 325bi; and (iii) the outlet conduit 356 is connected to the second cell outlet 325bo. [00140] Additionally, Figure 3B illustrates the first reflector surface 359d of the attenuated total reflector, as well a plurality of first bounces 329a (illustrated with short dashed ovals) in the first ATR region 359a, and a plurality of second bounces 329b (illustrated with dotted ovals) in the second ATR region 359b. As provided herein, (i) the first light beam 328a (illustrated in Figure 3A) directed at the proper angle at the first ATR region 359a results in the beam reflecting (bouncing 329a) between the first reflector surface 359d and the second reflector surface 359e (illustrated in Figure 3C) to create the first (“signal”) detection path; and (ii) the second light beam 328b (illustrated in Figure 3A) directed at the proper angle at the second ATR region 359b results in the beam reflecting (bouncing 329b) between the first reflector surface 359d and the second reflector surface 359e (illustrated in Figure 3C) to create the second (“reference”) detection path.

[00141] With this design, (i) at each first bounce 329a, the light penetrates slightly and evanescently couples into the sample 312a in the first test cell 325a; and (ii) at each second bounce 329b, the light penetrates slightly and evanescently couples into the sample 312b in the second test cell 325b. Subsequently (i) after one or more first bounces 329a, the light exits the first ATR region 359a as the first detection beam 326a (illustrated in Figure 3A); and (ii) after one or more second bounces 329b, the light exits the second ATR region 359ba as the second detection beam 326b (illustrated in Figure 3A).

[00142] Stated in another fashion, for each total internal reflection (bounce) 329a, 329b, an evanescent field will extend hundreds of nanometers into the respective sample 312a, 312b according to the well-known formula:

Equation (1 )

In Equation 1 , d_p is the 1/e optical penetration depth, lambda (A) is the wavelength of light, alpha (c ) is the incidence angle relative to the surface normal, ni and n2 are the indices of refraction for the attenuated total reflector and the sample (fluid) respectively. If optical absorbers are present in the sample fluid, then wavelength-dependent losses will occur at each beam reflection location along the sample interface thereby attenuating the intensity of light that reaches the detector.

[00143] Figure 3C is a cut-away view of the test cell assembly 324 taken on line 3C-3C in Figure 3A. Figure 3C illustrates (i) the first test cell 325a; (ii) the housing top 357a; (iii) the housing bottom 357b; (iv) the housing third side 357e; (v) the housing fourth side 357f; (vi) the housing divider 358; and (vi) the first ATR region 359a. In this design, the sample 312a flows in the first test cell 325a simultaneously over both the first reflector surface 359d, and the second reflector surface 359e. Alternatively, the test cell assembly 324 can be designed so that the sample 312a flows over only one of the reflector surfaces 359d, 359e, and/or the sample 312a can be non-flowing at the time of the analysis.

[001441 Figure 3C also illustrates the first light beam 328a directed at the first ATR region 359a, which results in the beam bouncing 329a between the first reflector surface 359d and the second reflector surface 359e (illustrated in Figure 3C) to create the first detector beam 326a.

[00145] It should be noted that the required number of bounces 329a, 329b will depend upon a number of factors, including (but not limited to) the sample 312a, 312b being analyzed, and the penetration depth on each bounce 329a, 329b. As alternative, nonexclusive examples, the processing assembly 310 can be designed so that the light beam bounces at least one, two, five, ten, twelve, fifteen, eighteen, twenty, twenty-five, thirty, thirty-five, of forty times within the respective test cell 325a, 325b. However, other values are possible. Generally speaking, the sensitivity will improve as the number of bounces 329a, 329b (and interactions with the sample 312a, 312b) and penetration depth increase.

[00146] Non-exclusive examples of the benefits of the flow cell assembly 324 of Figures 3A-3C include: (i) a compact nature, which allows for a smaller overall size; and (ii) ease of replacement of both test cells 325a, 325b at the same time when fouled.

[00147] Figure 4 is a simplified, top perspective view of a portion of yet another implementation of the processing assembly 410, including (i) a test cell assembly 424; (ii) a light source assembly 428 (illustrated as a box) that directs a first light beam 428a (illustrated as an arrow) and a second light beam 428b (illustrated as an arrow) at the test cell assembly 424; (iii) a first detector 430 that receives a first detector beam 326a (illustrated as an arrow) from the test cell assembly 424 and creates the upstream “signal” data; and (iv) a second detector 432 that receives a second detector beam 426b from the test cell assembly 424 and creates the downstream, “reference” data. It should be noted that the light source assembly 428 and the detectors 426a, 426b can be somewhat similar to the corresponding components described above in reference to Figure 1.

[00148] Additionally, it should be noted that the processing assembly 410 can also be designed to include a sample delivery system 14 (illustrated in Figure 1 ), a retainer receptacle 18 (illustrated in Figure 1 ), and/or a control-and-analysis system 20 (illustrated in Figure 1 ) that are somewhat similar to the corresponding components described above. [001491 The test cell assembly 424 can be substantially similar to the corresponding assembly described above in reference to Figures 3A-3C. In this design, (i) the inlet conduit 454 is connected to the first cell inlet 425ai; (ii) the connector conduit 452 connects the first cell outlet 425ao to the second cell inlet 425bi; and (iii) the outlet conduit 456 connects to the second cell outlet 425bo. However, in Figure 4, the location of the second cell inlet 425bi and the second cell outlet 425bo have been reversed from the previous implementation. As a result, the direction of the flow of the sample 412a in the first test cell 425a is opposite from the direction of the flow of the sample 412b in the second test cell 425b.

[00150] The time-domain differential spectroscopy method provided herein is well suited to monitor the sample accurately.

[00151] The signal power detected by the first detector is expressed in Equation (2) below, and the reference power detected by the second detector is expressed in Equation (3) below:

Equation (2) lr(t) = //. l(t)Rn exp(- ;.c(t-At)L_r) Equation (3)

In the Equations, I_s is the signal power (intensity) received by the first detector; I_r is the reference power received by the second detector;

is the beam splitter coefficient which defines how much optical power is going to the signal path and the reference path (optionally 50/50 or?] = 0.5). 5^ and R are wavelength dependent detector responsivities for the signal and reference detectors. C(t) is the time-dependent concentration of the sample, At is the time delay between a sample volume passing thru the reference beam and the sample beam.

is the absorption cross-section of the sample.

[00152] The processing assembly 10 is designed and built so that the signal path length is equal to the reference path length (L_s=L_r), and these terms can be referred to generically as L and L=L_r=L_s. Alternatively, for example, the processing assembly 10 can be designed so that the signal path length is longer or shorter than the reference path length. The value of the Ratio( ) = (1 -g S r R;.. can be determined by making a calibration measurment with no sample, c(t)=O.

[00153] Then, a negative log can be applied to the ratio as provided below to get a differential absorbance over time:

-log(ls/lr)= Ratio( ) -m[(c(t) - c(t-At)] L= Ratio( ) - At oi c’(t) L, Equation (4) where c’(t) is a derivative of the sample concentration over time assuming the change of concnetration is small on the time scale of At.

[00154] Integrating both sides of Equation (4) results in: Equation (5)

[00155] With the present design, the reconstructed absorbance is determined in Equation (5) while cancelling noise (caused by the light source assembly) because the noise terms are canceled out with the time-delayed signal and the reference path. Thus, utilizing the two detector paths allows for the cancellation of the noise terms of the light source assembly. As a result, the reconstructed absorbance provided herein is “noise- free” and has improved sensitivity.

[00156] Stated in another fashion, the original mathematical derivation of the fluidicdelay flow cell topology showing that the amplitude noise of the light source assembly is exactly cancelled while preserving the first derivative of the absorption spectrum which is directly proportional to the product of the absorption cross-section and analyte concentration. Furthermore, the absorption spectrum can be recovered fully through a time integration and optimal selection of the physical time delay (time of flight) of the analyte to travel between the signal and reference sampling locations. In one example, the minimum time delay (time of flight) should be set approximately equal to the update rate of the detector(s) so that at least one spectral scan is accomplished between the time the analyte moves from the signal sampling location to the reference sampling location. The time delay (time of flight) is equal to the product of the cross-sectional area (cm^A2) and the tube length between sample and reference sampling locations divided by the volumetric flow rate (mL/min). In one, non-exclusive implementation, then designing the flow cell, the analyzer can be set to have an update rate of approximately 0.1 seconds. In this example, for a six-millimeter inner diameter tube and a flow rate of 3000 mL/min, a tube length of at least 17.68 cm (6.96 inches) would suffice.

[001571 With the present design, there is a significant noise reduction that results from the near-perfect cancellation of the amplitude noise terms of the laser source assembly through direct ratioing.

[00158] Figures 5A-5D illustrate four simulation examples that demonstrate the reduction in noise with the current fluid analyzer design that utilizes time-domain differential spectroscopy. Figure 5A includes four graphs, namely (i) a top, first graph that details noisy laser amplitude for a first laser assembly versus time; (ii) a second from the top, second graph that details a signal detector response (solid line) and a reference detector response (dashed line) versus time for a first sample having first absorbance features; (iii) a third from the top, third graph that details the negative log of the ratio of what is shown in the second graph, with the signal detector response being a solid line and the reference detector response being a dashed line; and (iv) a bottom graph that details the reconstructed “noise-free” absorbance (solid line) and the “true absorbance” (dashed line) versus time for the first sample.

[00159] In the second graph, the responses are slightly delayed in time (e.g., one second) because of the separation distance between the signal path and the reference path.

[00160] The responses of the third graph can be determined using Equation (7) above. In the third graph, the slight delay in the responses is not visible. In this bottom graph, the reconstructed absorbance is a time integral of the signal that can be calculated using Equations (4) and (5) above. As is shown in the bottom graph, the actual absorbance is very close to the absorbance computed using Equation (5). This demonstrates that noise was significantly reduced with the present system. It should be noted that the curves in the bottom graph are overlapping, but have been deliberately offset slightly for visualization.

[00161] Similarly, Figure 5B includes four graphs, namely (i) a first graph that details noisy amplitude versus time for the first laser assembly; (ii) a second graph that details signal detector response (solid line) and reference detector response (dashed line) versus time for a second sample having second absorbance features; (iii) a third graph that details the negative log of the ratio of what is shown in the second graph; and (iv) a bottom graph details the reconstructed “noise-free” absorbance (solid line) and the “true absorbance” (dashed line) versus time. Comparing Figures 5A and 5B, the absorbance profile is different because of the different samples. However, in both cases, the actual absorbance is very close to the mathematical absorbance.

[00162] Further, Figure 5C includes four graphs, namely (i) a first graph that details noisy amplitude versus time for the first laser assembly; (ii) a second graph that details signal detector response (solid line) and reference detector response (dashed line) versus time for a third sample having third absorbance features; (iii) a third graph that details the negative log of the ratio of what is shown in the second graph; and (iv) a bottom graph details the reconstructed “noise-free” absorbance (solid line) and the “true absorbance” (dashed line) versus time. Comparing Figures 5A-5C, the absorbance profile is different because of the different samples. However, in each of these cases, the actual absorbance is very close to the mathematical absorbance.

[00163] Moreover, Figure 5D includes four graphs, namely (i) a first graph that details noisy amplitude versus time for a second laser assembly that is different than the first laser assembly; (ii) a second graph that details signal detector response (curve with small circles) and reference detector response (curve) versus time for the second sample having second absorbance features; (iii) a third graph that details the negative log of the ratio of what is shown in the second graph; and (iv) a bottom graph details the reconstructed “noise-free” absorbance (curve with small circles) and the “true absorbance” (curve) versus time. In this example, the second laser assembly generates a significant amount of white noise. However, in this example, the actual absorbance is still very close to the mathematical absorbance, demonstrating the reduction of noise by the present system. Further, the results in Figure 5D match the results of Figure 5B, even though different light source assemblies are being utilized.

[00164] Thus, the time-domain differential spectroscopy technique described above is insensitive to the absorption profile of the sample, and insensitive to laser noise. As a result, the reconstructed absorbance (which cancels out the noise) will be very accurate. [00165] In contrast, other methods have been proposed in the prior art to attempt to determine a sample's absorbance accurately. In one such prior art method, the measured absorbance in a signal path is compared to a baseline measurement of the intensity of the light source assembly (without the sample). This prior art method can be referred to as a baseline configuration. The baseline configuration is insensitive to changes in the temperature of the sample, which can influence absorbance, and other changes.

[00166] Figure 6 is a simplified, enlarged, cut-away illustration of a portion of another implementation of a processing assembly 610 for analyzing a sample 612. In this implementation, the processing assembly 610 includes (i) a test cell assembly 624 having a first test cell 625a that defines a first location 624a, and a spaced apart, second test cell 625b that defines a second location 624b; (ii) a light source assembly 628 that simultaneously directs a first light beam 628a at the first test cell 625a, and a second light beam 628b directed at the second test cell 625b; (iii) a first detector 630 that receives a first detector beam 626a exiting the first test cell 625a; (iv) a second detector 632 that receives a second detector beam 626b exiting the second test cell 625b; (v) an inlet conduit 654 that directs the sample 612 to the test cell assembly 624; and (vi) an outlet conduit 656 that receives the sample 612 exiting the test cell assembly 624.

[00167] It should be noted that the light source assembly 628, detectors 630, 632, and conduits 654, 656 can be somewhat similar to the corresponding components described above and illustrated in Figures 1-2D. Similarly, the data from the detectors 630, 632 can be used to spectrally analyze the sample 612.

[00168] Additionally, it should be noted that the processing assembly 610 can also be designed to include a sample delivery system 14 (illustrated in Figure 1 ), a retainer receptacle 18 (illustrated in Figure 1 ), and/or a control-and-analysis system 20 (illustrated in Figure 1 ) that are similar to the corresponding components described above.

[00169] Moreover, in Figure 6, each test cell 625a, 625b is again a transmission-style test cell, and the sample 612 in each test cell 625a, 625b is substantially simultaneously spectrally analyzed. However, in the non-exclusive implementation of Figure 6, the design and positioning of the test cells 625a, 625b are different. More specifically, in this design, (i) the first test cell 625a has a first sample path length 624d that the first light beam 628a travels through the first test cell 625a; (ii) the second test cell 625b has a second sample path length 624e that the second light beam 628b travels through the second test cell 625b; and (iii) the test cells 625a, 625b are designed so that the first sample path length 624d is different from the second sample path length 624e. For example, the first sample path length 624d can be shorter or longer than the second sample path length 624e. As alternative, non-exclusive implementations, the test cells 625a, 625b can be designed so that the first sample path length 624d is at least 2, 5, 10, 20, 30, 40, 50, 60, 70 or 80 percent different from the second sample path length 624e. However, other values are possible.

[00170] Moreover, the test cells 625a, 625b can be spaced apart and positioned in parallel. As a result, the sample 12 flowing from the inlet conduit 654 will be split with a first sample portion 612a flowing through the first test cell 625a, and a second sample portion 612b flowing through the second test cell 625b. With this design, the first sample portion 612a will be analyzed in the first test cell 625a, and the second sample portion 612b will be analyzed in the second test cell 625b. Subsequently, the two flows 612a, 612b can rejoin at the outlet conduit 656.

[00171] Figure 7 is a simplified schematic that illustrates the concept that an analyte (e.g., protein) displaces some of a mobile phase fluid (e.g., water) in a sample. More specially, Figure 7 illustrates (i) a container 700a (on the left) that is completely full of the mobile fluid (represented with “Ws”) at a first time; (ii) the container 700b (in the middle) at a later, second time in which the analyte (represented with “P’s”) is being added to the container 700b; and (iii) the container 700c at a subsequent third time in which the analyte was added, and a portion of the mobile phase fluid spills out. In this simplified example, N grams (moles) of the mobile phase fluid must spill out to make room for the M grams (moles) of analyte, provided the container 700a-700c has a constrained volume. The absence of the displaced mobile phase fluid will influence the absorbance. N is proportional to M, and this can be expressed as N = yM, where y will likely depend on the conformation of the analyte, and interconnection with other analytes in the solution.

[00172] Figure 8 is a simplified illustration of a portion of another implementation of the processing assembly 810 for analyzing a sample 812, which includes a fluid analyzer 816 that includes the test cell assembly 824, the detector assembly 826, and the light source assembly 828. In this implementation, the test cell assembly 824 can be similar to the designs described above. However, in this design, the light source assembly 826 is different. [00173] More specifically, in this implementation, the light source assembly 828 is a dual frequency comb design that includes (i) a first light source 828c that generates a first source beam 828d whose spectrum includes a first series 828e (illustrated with a plurality of peaks) of discrete, equally spaced apart frequency lines; (ii) a second light source 828f that generates a second source beam 828g whose spectrum includes a second series 828h (illustrated with a plurality of peaks) of discrete, equally spaced apart frequency lines that is offset from the first series 828e; (iii) a beam combiner 828i that spectrally combines the first source beam 828d with the second source beam 828g to generate a combination source beam 828j; and (iv) a beam splitter 836 that splits the combination source beam 828j into the first light beam 828a that is directed at the sample 812 flowing in the test cell assembly 824 in the first location 824a, and the second light beam 828b that is directed at the sample 812 flowing in the test cell assembly 824 in the second location 824b.

[00174] In one implementation, each light source 828c, 828f is a MIR laser, and this design is a mid-IR dual frequency comb-based setup whereby two frequency stabilized frequency combs having slight frequency offsets are used to generate signals on the signal and reference.

[00175] Figure 9A is a simplified end view of a portion of yet another implementation of a processing assembly 910, including a portion of a test cell assembly 924, a light source assembly 928 that directs a light beam 928a at the test cell assembly 924, and a detector assembly 926 that receives a detector beam 926a that exits the test cell assembly 924. It should be noted that the light source assembly 928 and the detector assembly 926 can be somewhat similar to the corresponding components described above and illustrated in Figure 1. Additionally, it should be noted that the processing assembly 910 can also be designed to include a sample delivery system 14 (illustrated in Figure 1 ), a retainer receptacle 18 (illustrated in Figure 1 ), and/or a control-and-analysis system 20 (illustrated in Figure 1 ) that are similar to the corresponding components described above.

[00176] In the non-exclusive implementation of Figure 9A, the test cell assembly 924 includes a cylindrical, annular ring-shaped test cell 925 that is at least partly made of an attenuated total reflection (“ATR”). With this unique design, as described in more detail below, the test cell 925 can be sized and shaped to match an inlet conduit 954 (illustrated in Figure 9B) and/or an outlet conduit 956 (illustrated in Figure 9B) of the processing assembly 910.

[001771 It should be noted that the processing assembly 910 of Figure 9A can be designed to use only a “signal” detection path with a single detector for the detector assembly 926. In this design, the processing assembly 910 does not utilize a time-domain differential absorption spectroscopy technique described above, which simultaneously acquires first data and second data. Alternatively, for example, the processing assembly 910 of Figure 9A can be designed to have both the “signal” detection path, and a “reference” detection path with a second detector as described above.

[00178] In the implementation of Figure 9A, the sample 12 can be flowing along a central axis “Ca” of the test cell 925, or non-flowing during the analysis within the test cell 925.

[00179] In the non-exclusive implementation of Figure 9A, the test cell 925 includes (i) a curved first surface 925a that defines at least a portion of a test internal channel 960 that receives the sample 12 during analysis; (ii) a curved second surface 925b that is spaced apart from the curved first surface 925a; and (iii) an access area 925c for receiving the light beam 928a that is reflected within the total reflection test cell 925. Further, the test cell 925 has a wall thickness 925d between the first surface 925a and the second surface 925b. The size, shape, and design of the test cell 925 can be varied pursuant to the teachings provided herein.

[00180] In the implementation of Figure 9A, the light source assembly 928 directs the incident light beam 928a into the test cell 925 through the access area 925c at the first surface 925a in a fashion so that the light beam 928a bounces 929 (each highlighted with a dashed oval) at least once off of the first surface 925a. The light bouncing (reflecting) in the test cell 925 can be referred to as the cell light beam 928a’. At each bounce 929, the cell light beam 928a’ penetrates a penetration depth “Pd” (greatly exaggerated in Figure 9A) into the sample 12. Subsequently, after one or more radial bounces 929, the cell light beam 928a’ exits the access area 925c as the detector beam 926a, which results from the absorption of the light 928a’, which evanescently couples into the sample 12 on each bounce 929 off the first surface 925a in accordance with Beer-Lambert principle. [00181] In one non-exclusive design, the cell light beam 928a’ to directed to experience a series of radial reflections between the inner, first surface 925a, and the outer, second surfaces 925b of the annular test cell 925, and therefore traverse a circular path generally orthogonal to the central axis “Ca” of the first surface 925a. Depending upon the design, the cell light beam 928a’ can propagate between the surfaces 925a, 925b in (i) a clockwise direction, or (ii) a counterclockwise direction relative to the central axis “Ca.” In any of the annular test cell 925 designs provided, the incident light beam 928a may be launched by the light source assembly 928 at an angle offset to a flow of the sample 12 in order to frustrate etalons or to create a corkscrew-like beam path around the test cell 925. In this design, the location where the incident light beam 928a enters the test cell 925 is spaced apart along the central axis Ca (and sample 12 flow direction) from the location where the detector beam 926b exits the test cell 925. Still alternatively, the processing assembly 910 can be designed so that the cell light beam 928a’ bounces along the test cell 925 in a path that is parallel to the central axis.

[00182] Non-exclusive examples of the benefits of the annual ring, ATR test cell 925 include: (i) its compact nature, which allows for a smaller overall size; (ii) the test cell 925 can be sized and shaped to match the other conduits in the system; and (iii) minimization of the distance the sample 12 contacts the flow cell 925 along the stream direction. Minimizing the distance of the first surface 925a along the fluid direction can minimize the temporal error of the measurement, as well as reduce the propensity for biofouling of the first surface 925a.

[00183] In the non-exclusive implementation of Figure 9A, the test cell 925 is defined by an annular, cylindrical ring-shaped attenuated total reflector. In this design, (i) the first surface 925a defines a cylindrical-shaped inner wall having a first radius R1 ; (ii) the second surface 925b defines a cylindrical-shaped outer wall having a second radius R2 that encircles the inner wall; (iii) the first surface 925a and the second surface 925b are substantially coaxial, and concentric; and (iv) the test cell 925 is solid between the surfaces 925a, 925b. Moreover, the test internal channel 960 has a test cross-sectional area, and a test cross-sectional shape. In a non-exclusive implementation of Figure 9A, the test cross-sectional shape is circular. [00184] In certain designs, the index of refraction of each of the surfaces 925a, 925b can be selected to suit the design of the system. In some implementations, the first surface 925a and/or the second surface 925b have an index of refraction of greater than approximately 1.35. For example, each surface 925a, 925b can have an index of refraction of greater than approximately 1.35. In alternative, non-exclusive implementations, one or both surfaces 925a, 925b has an index of refraction of at least 1.00, 1.25, 1.50, 2.50, or 4.00. It should be noted that the second surface 925b can be coated if necessary to achieve the desired index of refraction.

[00185] The type of material used for ATR test cell 925 can be varied to suit the wavelengths of the light beam 928a. Suitable materials for the ATR test cell 925 can include crystals such as germanium, Thallium halides, zinc selenide, silicon, diamond, Alpha-A^Os, ZrO2, ZnSe, KRS-5, AMTIR, or CdTe. These non-limiting, non-exclusive examples of ATR materials can have varying indices of refraction. Further, the material for the test cell 925 can be selected to achieve the design requirements of the processing assembly 910.

[00186] The access area 925c allows the light beam 928a to enter the test cell 925 and impinge upon the first surface 925a. Additionally, in certain implementations, the access area 925c allows the detector signal 926a to exit the test cell 925. The design of the assess area 925c can be varied to achieve the design requirements of the processing assembly 910. As non-exclusive examples, the access area 925c can include an aperture, a flat, a notch, and a groove in the second surface 925b.

[00187] In the non-exclusive implementation of Figure 9A, the access area 925c includes a first access region 925c1 , and a second access region 925c2 that is adjacent to the first access region 925c1 . In this design, (i) each access region 925c1 , 925c2 is a generally flat surface in the second surface 925b; (ii) the light beam 928a is directed through the first access region 925c1 and a chief ray of the incident light beam 928a is substantially perpendicular to first access region 925c1 , and (iii) the detector beam 926a exits through the second access region 925c2 and a chief ray of the detector beam 926a is substantially perpendicular to second access region 925c2.

[00188] However, other designs are possible. For example, the access area 925c can be designed so that (i) the light beam 928a enters and the detector beam 926a exits the same flat surface; (ii) the light beam 928a enters the access area 925c at an angle other than normal; and/or (iii) the detector beam 926a exits the access area 925c at an angle other than normal.

[00189] Further, in Figure 9A, the incident light beam 928a enters, and the detector beam 926a exits near each other in the test cell 925. Alternatively, the processing assembly 10 can be designed so that the light beam 928a enters, and the detector beam 926a exits at completely different, spaced apart locations in the test cell 925. With reference to an analog clock face, in the implementation of Figure 9A, the light beam 928a enters the test cell 925 and impinges on the first surface 925a at approximately the twelve position, and the detector beam 926a exits the test cell 925 leaving the first surface 925a at approximately the eleven position. As alternative, non-exclusive examples, the processing assembly 910 can be designed so that the incident light beam 928a impinges on the first surface 925a at the twelve positions, and the detector beam 926a exits the first surface 925a at the one, two, three, four, five, six, seven, eight, nine, ten, or twelve positions. In these non-exclusive examples, the first access region 925c1 can be near the twelve positions, and the second access region 925c2 can be near the one, two, three, four, five, six, seven, eight, nine, ten, or twelve positions. In summary, the one or more access regions 925c1 , 925c2 can be positioned wherever necessary in the second surface 925b to achieve the desired entry and exit locations.

[00190] Stated in another fashion, as alternative, non-exclusive examples, the processing assembly 910 can be designed so that the cell light beam 928a’ reflects within less than approximately ten, twenty, thirty, forty, fifty, sixty, seventy, eighty, or ninety percent of the annular test cell 925. In these designs, the annular test cell 925 can be made partly from the ATR material (e.g., an arch-shaped ATR crystal) or entirely from the ATR material.

[00191] Importantly, as provided herein, the characteristics of the processing assembly 910 can be adjusted and tuned by selecting the characteristics of the test cell 925 and/or selecting the characteristics of the light source assembly 928.

[00192] In Figure 9A, the light source assembly 928 and the test cell 925 are designed, positioned, and configured so that (i) the incident light beam 928a is directed at and passes through the access area 925c, and subsequently strikes the first surface 925a at an incidence angle 928b relative to normal 925e (perpendicular to the tangent) of the first surface 925a; (ii) the incidence angle 928b is greater than a critical angle 925f (relative to normal 925e) of the first surface 925a; and (iii) the light beam 928a propagates between the surfaces 925a, 925b with one or more reflections between the first surface 925a and the second surface 925b.

[00193] The acceptable values for the incidence angle 928b will depend upon a number of factors, including the critical angle 925f of the first surface 925a. The critical angle 925f of the first surface 925a will depend upon an index of refraction of the total internal reflector, test cell 925 (“crystal index”), and an index of refraction of the sample 12 (“sample index”). As a non-exclusive example, for a test cell 925 made of Germanium (crystal index ~ 4.1 ), and a sample 12 that is mostly water (sample index » 1.33), the critical angle 925f is approximately nineteen (19) degrees. Importantly, if the incidence angle 928b is less than the critical angle 925f, the light beam 928a will mainly pass through the first surface 925a without reflecting. Alternatively, if the incidence angle 928b is too large, the penetration distance will be very small.

[00194] As alternative, non-exclusive examples, and dependent upon the characteristics of the test cell 925 and the sample 12, the incidence angle 928b can be at least fifteen, eighteen, twenty, twenty-five, thirty, thirty-five, forty, forty-five, fifty, sixty, seventy, or eighty degrees. Stated in another fashion, in alternative, non-exclusive implementations, the incidence angle 928b is between approximately: (i) fifteen to seventy degrees; (ii) twenty to fifty degrees; (iii) twenty-five to forty-five degrees; (iv) twenty-five to thirty-five degrees; or (v) thirty to forty degrees. Stated in yet another fashion, the incidence angle 928b can be approximately fifteen, eighteen, twenty, twenty- five, thirty, thirty-five, forty, forty-five, fifty, sixty, seventy, or eighty degrees. However, other incidence angles 928b are possible. In the non-exclusive example of Figure 9A, the incidence angle 928b is thirty degrees.

[00195] Generally speaking, (i) lower incidence angles 928b result in a larger penetration depth Pd of the light beam 928a into the sample 12 at each bounce 929 than larger incidence angles 928b; (ii) the higher the incidence angle 928b, the less sensitive the penetration depth Pd is to angular changes of the incidence angle 928b; (iii) larger penetration depths Pd result in an improved sensitivity for the same number of bounces 929; and (iv) the sensitivity will increase as the number of bounces 929 increases for a given penetration depth Pd. A shift in incidence angle 928b can occur during the operation of the processing assembly 910 due to shifting of the components caused by vibration or temperature changes.

[00196] As a non-exclusive example, for a given test cell 925 and sample 12, a processing assembly 910 designed with an incidence angle 928b of twenty degrees will have a greater penetration depth Pd than a processing assembly 910 designed with an incidence angle 928b of fifty degrees. However, for a given test cell 925 and sample 12, a small change (“shift”) in the incidence angle 928b for the processing assembly 10 designed with the incidence angle 928b of twenty degrees will result in a relatively large change in the penetration depth Pd; while a corresponding small change in the incidence angle 928b for the processing assembly 10 designed with the incidence angle 928b of fifty degrees will result in a relatively small change in the penetration depth Pd. Thus, systems with a larger incidence angle 928b are more insensitive to changes in the equipment.

[00197] Stated in another fashion, a smaller incidence angle 928b will have greater penetration depth, but must be maintained with a higher alignment of the components, as compared to a system with a larger incidence angle 928b. In certain implementations, an incidence angle 928b of approximately thirty degrees is a nice compromise.

[00198] As provided herein, the light source assembly 928 and the test cell 925 can be designed, positioned, and configured to achieve the desired performance of the processing assembly 910 for typical working environments.

[00199] It should be noted that the magnitude of the penetration depth Pd and the performance of the processing assembly 910 can be varied according to a number of factors, including (but not limited to): (i) the incidence angle 928b; (ii) the wavelength of the incident light beam 928a; (iii) the polarization of the incident light beam 928a; (iv) a power of the incident light beam 928a; (iv) the material and dimensions of the test cell 925; and (v) the characteristics (e.g., temperature and composition) of the sample 12.

[00200] In certain implementations, the light source assembly 928 is controlled so that the center wavelength of the incident light beam 928a is changed over time over a desired spectral range as the sample 12 is flowing in the test cell 925. As alternative, non- exclusive examples, the desired spectral range can be at least five, ten, twenty, fifty, eighty, or one hundred percent of a MIR spectral range. In alternative, non-exclusive examples, the desired spectral range can be at least five, ten, twenty, fifty, eighty, or one hundred percent of (i) an ultra-violet spectral range, (ii) a visible light spectral range, (iii) a near-infrared spectral range, or (iv) a terahertz spectral range.

[00201] The polarization of the incident light beam 928a generated by the light source assembly 928 can be selected to achieve the desired penetration depth. As provided herein, the light source assembly 928 can be designed so that the incident light beam 928a has a linear polarization, a circular polarization, or an elliptical polarization. Generally speaking, in certain implementations, an incident light beam 928a with parallel polarization to the plane of incidence on the first surface 925a will result in larger penetration depths over the other polarizations. In certain designs, an incident light beam 928a with parallel polarization will result in almost two times greater penetration depths over the other polarizations.

[00202] The power (or intensity) of the incident light beam 928a generated by the light source assembly 928 will also influence the penetration depth, and potentially limit an acceptable path length of the cell light beam 928a’ in the test cell 925. Generally speaking, an incident light beam 928a with greater intensity will have a larger penetration depth, and be able to traverse a longer pathway in the test cell 925.

[00203] In alternative, non-exclusive examples, the cell light beam 928a’ will have a total pathway length in the test cell 925 of less than 5, 6, 7, 10, 15, 20, 25, 30, or 50 microns. However, other values are possible, depending upon the design of the light source assembly 928.

[00204] Additionally, in certain implementations, the light source assembly 928 is designed so that the incident light beam 928a is converging as it impinges on the first surface 925a. In this example, the incidence angle 928b refers to the position of a beam central axis 928c of the light beam 928a relative to normal 925e. For example, the light source assembly 928 can include an optical assembly 928d that properly focuses the incident light beam 928a. As non-exclusive examples, the optical assembly 928d can include one or more lenses (e.g., cylindrical or spherical lenses) or elements (e.g., mirrors). In contrast, in certain layouts, if the incident light beam is collimated (not shown), the cell light beam will rapidly diverge after a few bounces in the test cell, and not provide good results.

[002051 In the non-exclusive implementation of Figure 9A, (i) the incident light beam 928a has a thirty-degree incidence angle 928b and parallel polarization, (ii) the cell light beam 928’ bounces 929 seventeen times off of the first surface 925a, (iii) the cell light beam 928’ has approximately a six hundred nanometer penetration depth Pd per bounce 929, and (iv) the cell light beam 928’ has an effective penetration depth (d_e7 ) of ten microns. Alternatively, the processing assembly 910 can be designed so that the cell light beam 928a’ (i) bounces 929 more than seventeen or less than seventeen times; and/or (ii) penetration depth is greater or less than six hundred nanometers.

[00206] The required number of bounces 929 will depend upon a number of factors, including (but not limited to) the sample 12 being analyzed, and the penetration depth of the cell light beam 928a’ on each bounce 929. As alternative, non-exclusive examples, the processing assembly 910 can be designed so that the cell light beam 928a’ bounces 929 at least one, two, five, ten, twelve, fifteen, eighteen, twenty, twenty-five, thirty, thirty- five, of forty times within the test cell 925. However, other values are possible. Generally speaking, the sensitivity will improve as the number of bounces 929 (and interactions with the sample 12) and penetration depth increase.

[00207] In certain implementations, a processing assembly 910 designed to have (i) approximately thirty-degree incidence angle 928b and parallel polarization; and (ii) approximately fifteen to twenty bounces 929 in a single path around the test cell 925, will result in a total pathway of fifteen to twenty microns and approximately one-micrometer penetration depth per bounce. This length of pathway is ideal for a Quantum Cascadebased light source assembly 928; and the system is only moderately sensitive to changes to the incidence angle 928b. However, other values can be used.

[00208] Further, the characteristics of the processing assembly 910 can be adjusted and tuned by (i) selecting the size of the first surface 925a, and (ii) selecting the size of the second surface 925b. As a non-exclusive example, (i) the size of the first (inner) radius R1 can be selected to match the size of the inlet conduit 954 or the outlet conduit 956, and/or (ii) the size of the second (outer) radius R2 can be selected to achieve a desired number of bounces 929 with the desired incidence angle 928b. As alternative, non-exclusive examples, the test cell 925 can have (i) an inner radius R1 of approximately 0.3, 0.4, 0.5, 1 , 2, 5, 10, 15, 20, 30, 40, or 50 millimeters; and/or (ii) a wall thickness 925d of approximately 0.25, 0.5, 1 , 5, 10, 15, 20, or 24 millimeters

[00209] Figure 9B is a simplified side perspective, cut-away view of the test cell 925 of Figure 9A with the inner surface 925a and the outer surface 925b. Figure 9B also illustrates a portion of the cell light beam 928a’ that is reflecting within the test cell 925 between the surfaces 925a, 925b while interacting with the sample 12 (illustrated with an arrow) in the test cell 925.

[00210] Additionally, Figure 9B illustrates (i) a portion of an inlet conduit 954 that is in fluid communication with and delivers the sample 12 to the test cell 925; and (ii) a portion of an outlet conduit 956 that is in fluid communication with and allows for the sample 12 to exit test cell 925. As a non-exclusive example, (i) the inlet conduit 954 can be in fluid communication with the sample delivery system 14 (illustrated in Figure 1 ) to deliver the sample 12 to the test cell 925; and/or (i) the outlet conduit 956 can be in fluid communication with the retainer receptacle 18 (illustrated in Figure 1 ) to remove the sample 12 from the test cell 925.

[00211] As non-exclusive examples, each conduit 954, 956 can be a flexible tube, cylindrical tubing, or any other suitable conduit. In Figure 9B, the conduits 954, 956 are illustrated as being fixedly attached to the test cell 925. Alternatively, in certain implementations, the conduits 954, 956 can be selectively, and removably attached to the test cell 925. With this design, the test cell 925 can be easily replaced when it becomes fouled or damaged.

[00212] The inlet conduit 954 defines an inlet channel 954a that receives and transports the sample 12 to the test cell 925. Further, the inlet channel 954a has an inlet cross- sectional area and an inlet cross-sectional shape. In the non-exclusive design of Figure 9B, the inlet cross-sectional shape is circular, and inlet channel 954a has an inlet diameter 954b.

[00213] Similarly, the outlet conduit 956 defines an outlet channel 956a that receives and transports the sample 12 from the test cell 925. Further, the outlet channel 956a has an outlet cross-sectional area and an outlet cross-sectional shape. In the non-exclusive design of Figure 9B, the outlet cross-sectional shape is circular, and outlet channel 956a has an outlet diameter 956b.

[002141 Uniquely, in certain implementations, (i) the test cell 925 is designed so that the test internal channel 960 approximately (or exactly) matches and corresponds to the inlet channel 954a, and/or (ii) the test cell 925 is designed so that the test internal channel 960 approximately (or exactly) matches and corresponds to the outlet channel 956a. With this design, the channels 960, 954a, 956a can be perfectly matched. As a result, the sample 12 will flow more smoothly (be less turbulent) in the test cell 925, and dead volumes and mixing of the sample 12 will be minimized. This will result in more accurate measurements because the light beam 925a will have better interaction with the sample 12. In contrast, (i) changes in shapes and/or sizes between the inlet channel 954a and the test internal channel 960 will result in turbulent flow, mixing, and dead volumes (e.g., air) in the sample 12 in the test cell 925; and/or (ii) changes in shapes and/or sizes between the test internal channel 960 and the outlet channel 956a will result in turbulent flow, mixing, and dead volumes in the sample 12 in the test cell 925. The turbulence and dead volumes will adversely influence the analysis of the sample 12.

[00215] Stated in another fashion, the test cross-sectional shape is approximately the same as the inlet cross-sectional shape and/or the outlet cross-sectional shape. For example, a cylindrical conduit is often used for the inlet conduit 954 and the outlet conduit 956. In this design, (i) the inlet cross-sectional shape and the outlet cross-sectional shape are circular; and (ii) the test cell 925 can be designed so that the test cross-sectional shape is a circular cross-sectional shape. Alternatively, other shapes are possible, such as oval shapes, square shapes, rectangular shapes, or polygonal shapes.

[00216] Additionally, the test cross-sectional area is approximately equal to the inlet cross-sectional area and/or the outlet cross-sectional area. As used herein, “approximately equal to” is understood to mean within +/- five percent. Stated in a different fashion, in alternative, non-exclusive implementations, (i) the test cross-sectional area is within 0.25, 0.5, 1 , 1.5, 2, 3, 4, 5, or 10 percent of the inlet cross-sectional area; and/or (i) the test cross-sectional area is within 0.25, 0.5, 1 , 1.5, 2, 3, 4, 5, or 10 percent of the outlet cross-sectional area. Non-exclusive examples of suitable cross-sectional areas include at least approximately 1 mm², 3mm², 5mm², 8mm², 10mm², 15mm², 25mm², 100mm², 200 mm², or 300 mm² .

[002171 For the implementation illustrated in Figure 9B, the test internal channel 960, the inlet channel 954a, and the outlet channel 956a each have a circular cross-section. Thus, the test internal channel 960 has a test diameter 960a, the inlet channel 954a has an inlet diameter 954b, and the outlet channel 956a has an outlet diameter 956b. In the design of Figure 9B, the test diameter 960a is approximately equal to the inlet diameter 954b, and/or the outlet diameter 956b. As used herein, “approximately equal to” again means within +/- five percent. Stated in a different fashion, in alternative, non-exclusive implementations, (i) the test diameter 960a is within 0.25, 0.5, 1 , 1.5, 2, 3, 4, 5, or 10 percent of the inlet diameter 954b; and/or (i) the test diameter 960a is within 0.25, 0.5, 1 , 1.5, 2, 3, 4, 5, or 10 percent of the outlet diameter 956b. In one implementation, the diameters 954b, 956b, 960a match exactly.

[00218] Non-exclusive examples of suitable conduits 954, 956 have a diameter of approximately 14, 1 , %, 1 , 2, or 4 inches.

[00219] Figure 9B also illustrates that the first surface 925a can include a first surface coating 925g (represented with x’s). Non-exclusive characteristics of suitable first surface coatings 925g include (i) improving the chemical stability of the first surface 925a, and/or (ii) inhibiting the binding of biological materials to the first surface 925a. The first surface coating 925g can be partially hydrophilic or partially hydrophobic. The first surface coating 925g can be at least partially formed from a metal.

[002201 It should be noted that a test cell length 925h of the test cell 925 measured along the central axis (Ca) can also be varied. Generally, the shorter the test cell length 925h, the less likely the test cell 925 will get fouled and the less costly the test cell 925 is to make. As non-exclusive examples, the test cell 925 can have a test cell length 925h of less than approximately 1 , 1 .5, 2, 3, 5, 10, 20, or 50 millimeters. However, other values can be utilized.

[00221] As a non-exclusive example, a solid, relatively long cylindrical-shaped attenuated total reflector can be cored to the appropriate radius, polished, and optionally coated to create the inner surface 925a. Next, the outer circumference can be machined and polished to create the outer surface 925b. Subsequently, the access area can be made. Finally, the long, attenuated total reflector can cut into a plurality of small test cells 925 with the desired test cell length 925h.

[002221 Figure 9C is another illustration of the test cell 925 of Figure 9A, including the first surface 925a, and the second surface 925b. As provided above, the characteristics of the test cell 925 and the light source assembly 928 (illustrated in Figure 9A) can be varied and adjusted to achieve the desired performance characteristics. The relationship between the design parameters of the inner radius R1 , the outer radius R2, the incidence angle “0” 928b, and number of bounces “N” 929 are explained in more detail with reference to Figure 9C. In Figure 9C, dl represents a separation distance between adjacent bounces 929. In this example, (i) the separation distance is equal to two times pi divided by the number of bounces, and multiplied by the inner radius R1 (dl=(2n7N) R 1 ), and (ii) the outer radius is equal to the separation distance divided by two, and subsequently divided by the tangent of the incident angle 928b plus the inner radius (R2=(dl/2)/tan(0)+Rl).

[00223] In one, non-exclusive example, (i) an inner radius of three millimeters (R1 =3mm) is chosen to match the inlet conduit 954 (illustrated in Figure 9B) and/or the outlet conduit 956 (illustrated in Figure 9B); (ii) an incidence angle 928b of thirty degrees (0 = 30°) is selected; and (iii) it is desired to have seventeen bounces 929 (N=17). As a result of these design choices, the separation distance is equal to 1.1 millimeters (dl=(2ir/17) x 3 mm= 1.1 mm); and the outer radius is equal to 3.95 millimeters (R2=(1 .1 mm/2)/tan(30)+3 mm= 3.95 mm).

[00224] In an alternative, non-exclusive example, (i) an inner radius of three millimeters (R1 =3mm) is again chosen to match the inlet conduit 954 and/or the outlet conduit 956; and (ii) an incidence angle 928b of thirty degrees (0 = 30°) is again selected. However, in this example, it is desired to have thirty-five bounces 929 (N=35). As a result of these design choices, the separation distance is equal to 0.54 millimeters (dl=(2n735) x 3 mm= 0.54 mm); and the outer radius is equal to 3.48 millimeters (R2=(0.54mm/2)/tan(30)+3 mm= 3.48 mm). In this design, the effective penetration depth will be 21 microns at each bounce.

[00225] In still another, alternative, non-exclusive example, an inner radius of three millimeters (R1=3mm) is again chosen to match the inlet conduit 954 and/or the outlet conduit 956. However, in this example, it is desired to have (i) an incidence angle 928b of forty-five degrees (0 = 45°); and (ii) thirteen bounces 929 (N=13). As a result of these design choices, the separation distance is equal to 1 .45 millimeters (dl=(2ir/13) x 3 mm= 1.45 mm); and the outer radius is equal to 3.72 millimeters (R2=(1 .45mm/2)/tan(45)+3 mm= 3.48 mm). In this design, the effective penetration depth will be 5 microns at each bounce.

[00226] As is evident from these examples, the characteristics of the system can be tuned by adjusting the characteristics described above. In the examples above, the inner radius R1 , the incidence angle 0, and the number of bounces N are the selected design parameters, and the outer radius R2 can be determined to achieve these parameters.

[00227] As another, non-exclusive example, a test cell (not shown) can be designed to provide for a thirty-five bounces, a thirty-degree incidence angle, a penetration depth of six hundred nanometers, and an effective penetration depth (d_efr) of twenty-one microns. [00228] Figure 10 is a simplified illustration of a portion of yet another processing assembly 1010. In this design, the processing assembly 1010 includes a signal test cell 1025s, a reference test cell 1025r, a detector assembly 1026, and a light source assembly 1028. Further, (i) each test cell 1025s, 1025r can be similar to the test cell 925 described above in reference to Figures 9A-9C; and (ii) the light source assembly 1028 and the detector assembly 1026 can be similar to the corresponding components described above and illustrated in Figure 1 . It should be noted that the processing assembly 1010 can be also designed to include a sample delivery system 14 (illustrated in Figure 1 ), a retainer receptacle 18 (illustrated in Figure 1 ), and/or a control-and-analysis system 20 (illustrated in Figure 1 ).

[00229] In Figure 10, the processing assembly 1010 can utilize the time-domain differential absorption spectroscopy technique described above with reference to Figure 1 , which simultaneously acquires (i) first data 1021 a (illustrated with a dashed block) at a first location 1024a; and (ii) second data 1021 b (illustrated with a dashed block) at a second location 1024b. In this design, (i) the sample 12 flows from the first location 1024a in the signal test cell 1025s to the second location 1024b in the reference test cell 1025r with some time delay therebetween; and (ii) the processing assembly 1010 has both a “signal” detection path at the first location 1024a, and a “reference” detection path at the second location 1024b. The sample at the second location 1024b is referenced with 12’ to designate that it may have a different composition than the sample 12 at the first location 1024a.

[00230] In Figure 10, the signal test cell 1025s with the first location 1024a, and the reference test cell 1025r with the second location 1024b are illustrated as being side-by- side. Importantly, however, the test cells 1025s, 1025r can be connected in series with the sample 12 flowing from the signal test cell 1025s to the reference test cell 1025r. Alternatively, test cells 1025s, 1025r be arranged to be coaxial or substantially coaxial.

[00231] In the non-exclusive example of Figure 10, the signal test cell 1025s and the reference test cell 1025r are two separate components and are spaced apart. Alternatively, a single test cell (not shown in Figure 10) that is relatively long could be utilized. In this design, for example, the first location 1024a, and the second location 1024b, can be at different ends of the long test cell.

[00232] In Figure 10, the first location 1024a is upstream of the second location 1024b. The amount of separation distance (not shown in Figure 10) between the first location 1024a and the second location 1024b can be varied in accordance with the update rate of the detectors assembly 1026 and the linear velocity of the sample 12. In Figure 10, the separation distance can be similar to the corresponding separation distance 24c described above in reference to Figure 1 to achieve the desired time domain separation. [00233] It should be noted that the test cells 1025s, 1025r of Figure 10 are designed to preserve the quality of the moving sample 12.

[00234] The light source assembly 1028 substantially simultaneously (i) directs the first incident light beam 1028a at the desired incidence angle 928b (illustrated in Figure 9A) at the signal test cell 1025s, and (ii) directs the second incident light beam 1028b at the desired incidence angle 928b at the reference test cell 1025r. In one implementation, the light source assembly 1028 includes an optical assembly 1028d (similar to the one described in reference to Figure 9A) for each beam path, so that each incident light beam 1028a, 1028b is a converging beam. Stated in another fashion, in one implementation, (i) the first incident light beam 1028a is converging at the signal test cell 1025s, and (ii) the second light beam 1028b is converging at the reference test cell 1025r. [00235] In one implementation, the detector assembly 1026 substantially simultaneously captures the data 1021 a, 1021 b at approximately the same wavelength (or set of wavelengths), at the two spaced apart locations 1024a, 1024b. Subsequently, that data 1021 a, 1021 b can be used by the control-and-analysis system 20 to spectrally analyze the sample 12. In Figure 10, the detector assembly 1026 again includes the first detector 1030 and the second detector 1032, which can be similar to the corresponding components described above.

[00236] In Figure 10, (i) the first light beam 1028a directed at the signal test cell 1025s is bounced within the signal test cell 1025s, and is collected by the first detector 1030, and (ii) the second light beam 1028b directed at the reference test cell 1025r is bounced within the reference test cell 1025r, and is collected by the second detector 1032.

[00237] With this design, the processing assembly 1010 spectrally analyzes the sample 12, 12’ at the two, spaced apart locations 1024a, 1024b, at approximately the same time, and approximately the same wavelength (or wavelengths).

[00238] Figure 11 is a simplified, cut-away illustration of an inlet conduit 1154, a signal test cell 1125s (with the first location 1124a), a connector conduit 1152, a reference test cell 1025r (with the second location 1124b), and an outlet conduit 1156. In this example, the connector conduit 1152 connects and separates the test cells 1125s, 1125r; and the length of the connector conduit 152 sets the separation distance 1124c. A portion of a signal, cell light beam 1128a’s in the signal test cell 1125s, and a portion of a reference, cell light beam 1128a’r in the reference test cell 1125r are also illustrated in Figure 11. This arrangement can be used in the processing assembly 1010 of Figure 10 with the flowing sample 12.

[00239] In the example of Figure 11 , the test cells 1125s, 1125r, and the connector conduit 1152 are aligned coaxially. Further, the internal dimensions of these components can be matched. Alternatively, for example, the connector conduit 1152 can be a flexible tube, and the test cells 1125s, 1125r can be positioned to not be coaxial.

[00240] Figure 12 is a simplified, cut-away illustration of the inlet conduit 1254, the outlet conduit 1256, and another implementation of the test cell 1225. In this design, the test cell 1225 is relatively long and defines both the first location 1224a, and the second location 1224b that are spaced apart at a separation distance 1224c and aligned coaxially. It should be noted that a portion of a signal, cell light beam 1228a’s in the test cell 1225, and a portion of a reference, cell light beam 1228a’r in the reference test cell 1125r are also illustrated in Figure 12. This arrangement can be used in the processing assembly 1010 of Figure 10 with the flowing sample 12.

[00241] Figure 13 is a simplified view of still another implementation of a test cell 1325 that can be used in the processing assemblies 910, 1010 described above. The incident light beam 1328, the cell light beam 1328a’ that is rebounding in the test cell 1325, and the detector beam 1326a are also illustrated in Figure 13.

[00242] In this example, the test cell 1325 includes a first surface 1325a, a second surface 1325b, and an access area 1325c that are somewhat similar to the corresponding components of the test cell 925 described above and illustrated in Figure 9A. However, in Figure 13, the second surface 1325b is generally rectangular shaped instead of being cylindrical. Further, in the simplified illustration in Figure 13, the cell light beam 1328a’ only bounces four times off the first surface 1325a. However, this design can be modified to achieve the desired number of bounces off the first surface 1325a.

[00243] As mentioned above, for the test cells 925 -1325 illustrated in Figure 9A-13, in certain implementations, the incident light beam 928a-1328 should be converging. In contrast, if the incident light beam 928a-1328a is collimated, this beam will transition into a divergent beam after a number of interior bounces due to the larger negative power of the first surface 925a-1325a relative to the second surface 925b-1325b. This would result in: (a) stronger overlap of the beam with itself, leading to parasitic etalons, (b) limiting the number of bounces to a small number, and (c) causing the detector beam 926a-1326a to be too large to escape the access area 925c-1325c.

[00244] In general, the input light beam should be tailored to efficiently couple into the optical system comprising test cell and detector. As provided herein, the limitations described above can be overcome by properly designing the test cell 925-1325, and directing the incident light beam 928a-1328a to converge on the first surface 925a-1325a at the appropriate incident angle 928b. Stated in another fashion, there exists a family of solutions that allows for the light beam properties to be periodically stable over an arbitrary number of bounces in a properly designed, test cell 925 -1325. [00245] Figure 14 is a simplified end view of a test cell 1425 that includes the first surface 1425a having the inner radius R1 , and the second surface 1425b having the outer radius R2. The access area is not shown in Figure 14. Moreover, in Figure 14, the incident light beam 1428a is represented with three arrows that illustrate that the incident light beam 1428a is still converging when it impinges on the first surface 1425a. Stated in another fashion, the incident light beam 1428a is represented with three arrows, and each arrow represents a separate, converging ray. Further, the incident light beam 1428a has a beam central axis 1428c and a central (or chief) ray 1428d that is coaxial with the beam central axis 1428c.

[00246] Figure 14 illustrates the trivial case in which the chief ray 1428d (aligned along the beam central axis 1428c) of the incident light beam 1428a has an incident angle of zero degrees, and is normal with respect to both the outer second surface 1425b, and inner first surface 1425a. In this case, both the first surface 1425a and the second surface 1425B exhibit zero effective optical power, thereby creating a stable resonator. Stated in another fashion, in this non-exclusive example, the light beam 1428a is directed at the surfaces 1425a, 1425b at an incidence angle of zero degrees, and as a result thereof, the light beam 1428a resonates between the surfaces 1425a, 1425b (assuming these surfaces reflect light). In this example, the beam 1428a does not ‘walk’ around the annular test cell 1425 because the incidence angle is zero. This is not a practical solution but is useful for the purposes of illustrating the concept of a 4f Fourier optical system as it applies to the present design.

[00247] Figure 14 also illustrates that the converging incident light beam 1428a directed by the light source assembly 1028 (illustrated in Figure 10) has (i) a virtual image point 1470 (represented by a circle) that is at the central axis “Ca” of the test cell 1425; and (ii) a virtual object point 1472 (represented with a triangle) that is at the central axis “Ca” of the test cell 1425. In the example of Figure 14, the virtual object point 1474 is co-located with the virtual image point 1472 within the inner surface 1425a.

[00248] Additionally, Figure 14, illustrates (i) a pivot point 1470 (represented by a square) of the incident light beam 1428a, which is located at where the chief ray 1428d intersects the first surface 1425a; and (ii) a “2f surface” is approximated with the dashed circle 1476, where “2f” is twice the focal length. In this design, (i) the focal length is equal to the radius (R1 ) of the first surface 1425a, and (ii) the incident light beam 1428a is intentionally focused on the virtual image point 1470 that is located on the 2f surface 1476.

[00249] As provided herein, when the converging incident light beam 1428a directed by the light source assembly 1028 at the test cell 1425 is properly focused (converging) on the 2f surface 1476, a 4F Fourier optical resonator is created between the surfaces 1425a, 1425b. When the 4F Fourier optical resonator is created, the beam will image to itself at 4f with the same magnification. With the proper design, a stable resonator can be created, and the beam properties will be periodically stable over an arbitrary number of bounces with the test cell 1425.

[00250] In certain implementations, the focus of the incident light beam 1428a can be slightly adjusted as necessary, until the stable resonator is created. Stated in another fashion, with the proper focusing of the incident light beam 1428a, the beam properties will be periodically stable over an arbitrary number of bounces along the annulus of the test cell assembly 1424.

[00251] In certain implementations, the test cell and the incidence angle are selected based on stable resonator theory. A stable optical resonator consists of two surfaces with radii of curvature R1 and R2 separated by an optical distance of geometrical spacing between the reflective surfaces that meets a stability criterion. The range of optical distances which is determined to be stable is determined by a condition that a ray launched inside the resonator parallel to the optical axis remains inside the resonator after a suitably large number of bounces.

[00252] Figure 15 is a simplified view of a test cell 1525 including a first surface 1525a, and a second surface 1525b, and the test cell 1525 can be used to analyze a sample 12 (illustrated in Figure 1 ). The access area is again not shown in Figure 15. Moreover, in Figure 15, an incident light beam 1528a is represented with three arrows that illustrate that the incident light beam 1528a is still converging when it impinges on the first surface 1525a.

[00253] In the non-exclusive implementation of Figure 15, the incident light beam 1528a is directed to have a non-zero incident angle 1528b that is greater than the critical angle 925f (illustrated in Figure 9A). More specifically, in this example, the incident light beam 1528a has an incident angle 1528b of thirty degrees. However, other incident angles 1528b are possible as long as the incidence angle 1528b is greater than the critical angle 925f. With this design, the light beam 1528a’ resonates between the surfaces 1525a, 1525b and “walks” around the annulus. In Figure 15, the converging incidence light beam 1528a directed at the first surface 1525a is reflected as a diverging light beam 1528a’ directed at the second surface 1525b. In this example, the beam 1528a’ continues to “walk” around the annulus of the test cell 1525 with the beam 1528a’ transitioning between converging and diverging conditions, but in a periodical pattern.

[00254] Figure 15 also illustrates that the converging incident light beam 1528a directed by the light source assembly 1028 (illustrated in Figure 10) has (i) a virtual image point 1570 (represented by a circle) that is positioned on the “2f surface” approximated by the circle 1576 spaced apart from the central axis “Ca” of the test cell 1525; and (ii) a virtual object point 1572 (represented with a triangle) that is also positioned on the “2f surface” approximated by the circle 1576 spaced apart from the central axis “Ca.” In the example of Figure 15, the virtual object point 1574 is spaced apart from the virtual image point 1572 on the “2f surface” 1576.

[00255] As provided herein, when the converging incident light beam 1528a is directed at the test cell 1525 and is properly focused (converging) on the 2f surface 1576, a 4F Fourier optical resonator is created between the surfaces 1525a, 1525b. With the proper design, a stable resonator can be created, and the beam properties will be periodically stable over an arbitrary number of bounces with the test cell 1525.

[00256] Figure 16 is a simplified view of the test cell 1525 of Figure 15, including the first surface 1525a and the second surface 1525b at a subsequent time. The access area is again not shown in Figure 16. As illustrated in Figure 16, the light beam 1528a’ resonates between the surfaces 1525a, 1525b and propagates around the annulus of the test cell 1525. As described above, the light beam 1528a’ reflected from the first surface 1525a and directed at the second surface 1525b is diverging. Subsequently, the light beam 1628a’ reflected from the second surface 1525b and directed back at the first surface 1525a is converging. As illustrated, the beam 1528a’, 1628a’ continues to propagate around the annulus of the test cell 1525 with the beam 1528a’, 1628’ transitioning between converging and diverging conditions, but in a periodical pattern. [00257] Figure 17 is a simplified view of a portion of yet another implementation of a processing assembly 1710, including a test cell 1725, a light source assembly 1728 that directs an incident light beam 1728a at the test cell 1725, and a detector assembly 1726 that receives a detector beam 1726a that exits the test cell 1725. It should be noted that the light source assembly 1828 and the detector assembly 1726 can be somewhat similar to the corresponding components described above and illustrated in Figure 1. Additionally, it should be noted that the processing assembly 1710 can be also designed to include a sample delivery system 14 (illustrated in Figure 1 ), a retainer receptacle 18 (illustrated in Figure 1 ), and/or a control-and-analysis system 20 (illustrated in Figure 1 ) that are similar to the corresponding components described above.

[00258] In Figure 17, the test cell 1725 is, again, cylindrical, annular ring-shaped shaped, and is at least partly made of an attenuated total reflection. With this unique design, as described in more detail below, the test cell 1725 can be sized and shaped to match an inlet conduit 954 (illustrated in Figure 9B) and/or an outlet conduit 956 (illustrated in Figure 9B) of the processing assembly 1710.

[00259] It should be noted that the processing assembly 1710 of Figure 17 can be designed to use only a “signal” detection path with a single detector for the detector assembly 1726. In this design, the processing assembly 1710 does not utilize a timedomain differential absorption spectroscopy technique described above, which simultaneously acquires first data and second data. Alternatively, for example, the processing assembly 1710 can be designed with the “signal” detection path, and a “reference” detection path with a second detector for the detector assembly 1726 as described above.

[00260] In the implementation of Figure 17, the sample 12 can be flowing along a central axis “Ca” of the test cell 1725, or non-flowing during the analysis within the test cell 1725.

[00261] In Figure 17, the test cell 1725 is somewhat similar to the test cell 925 described above in reference to Figures 9A-9C, and includes (i) a curved first surface 1725a; (ii) a curved second surface 1725b; and (iii) an access area 1725c. However, in the implementation of Figure 17, the components are arranged and designed so that the cell light beam 1728a’ only bounces 1729 ten times on the first surface 1725a, and the cell light beam 1728a’ only traverses about one-half the annulus of the test cell 1725.

[002621 In Figure 17, (i) the access area 1725 includes a first access region 1725c1 and a second assess region 1725c2 that is spaced apart from the first access region 1725c1 ; (ii) the light source assembly 1728 directs the incident light beam 1728a through the first access region 1725c1 at the desired incidence angle 1728b at the first surface 1725a; (iii) the detector beam 1726a exits through the second access region 1725c2; (iv) the incident light beam 1728a enters the first access region 1725c1 at a normal angle; and (v) the detector beam 1726a exits the second access region 1725c2 an angle other than normal. However, other designs (e.g., with varying entry and exit angles) are possible.

[00263] As provided above, in Figure 17, the cell light beam 1728a’ only traverses about one-half the annulus of the test cell 1725. In this design, the entire test cell 1725 can be made as a unitary, one-piece, ATR crystal material (described above in reference to Figure 9A). Alternatively, the test cell 1725 can be a multi-piece construction. For example, in Figure 17, (i) the test cell 1725 includes an arch-shaped first cell segment 1778a; (ii) an arch-shaped second cell segment 1778b; (iii) a segment fastener 1778c (e.g., via epoxy or other adhesives) that fixedly secures the cell segments 1778a, 1778b together to form the annular shaped test cell 1725; and (iv) each cell segment 1778a, 1778b extends approximately one half of the annulus of the test cell 1725. Still alternatively, the multi-piece construction of the test cell 1725 can include more than two cell segments 1778a, 1778b, and/or one or more of the cell segments 1778a, 1778b can be a smaller or larger segment of the annulus than is illustrated in Figure 17. For example, one or more of the cell segments 1778a, 1778b can have an arc shape of approximately 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 200, 250, 270, 300, or 350 degrees.

[00264] In Figure 17, the cell light beam 1728a’ reflects within the first cell segment 1778a, and the first cell segment 1778a is made of a suitable attenuated total reflector material. Further, the second cell segment 1778b can be made of any suitable material, e.g., plastic, or glass. Moreover, in the non-exclusive implementation of Figure 17, the access regions 1725c1 , 1725c2 are formed in the first cell segment 1778a, and the incident light beam 1728a and the detector beam 1726a travel through a portion of the second cell segment 1778b. Alternatively, the test cell 1725 can be designed so that one or both beams 1728a, 1726a does not travel through the second cell segment 1778b.

[002651 In summary, in Figure 17, the incident light beam 1728a enters, and the detector beam 1726a exits at completely different, spaced apart locations in the test cell 1725. With reference to an analog clock face, in Figure 17, the light beam 1728a enters the test cell 1725 and impinges on the first surface 1725a at approximately the twelve position, and the detector beam 1726a exits the test cell 2725 leaving the first surface 1725a at approximately the six position. As alternative, non-exclusive examples, the processing assembly 1710 can be designed so that the incident light beam 1728a impinges on the first surface 1725a near the twelve o’clock position, and the detector beam 1726a exits the first surface 1725a near the one-, two-, three-, four-, five-, six-, seven-, eight-, nine-, ten-, eleven-, or twelve o’clock position.

[00266] In Figure 17, the first access region 1725c1 is near the twelve o’ clock position, and the second access region 1725c2 is near the six o’ clock position. However, these access regions 1725c1 , 1725c2 can be at different positions than shown in Figure 17.

[00267] Moreover, in Figure 17, the processing assembly 1710 is designed so that the cell light beam 1728a’ reflects within approximately fifty percent of the annular test cell 1725. Alternatively, the processing assembly 1710 can be designed so that the cell light beam 1728a’ reflects within less than approximately ten, twenty, thirty, forty, fifty, sixty, seventy, eighty, or ninety percent of the annular test cell 1725.

[00268] Figure 18 is a chart that illustrates the relationship between effective penetration depth and incidence angle for an annular, attenuated total reflector test cell made of germanium, and having a critical angle of approximately 19 degrees. In this chart, as the incidence angle is increased, the effective penetration depth decreases, and the number of bounces required to obtain sufficient information increases.

[00269] Figure 19A is a simplified, cut-away view of another implementation of a portion of the processing assembly 1910 including (i) a modular, test cell assembly 1924 that includes a test cell 1925, (ii) an inlet conduit 1954 that directs the sample 12 (represented with an arrow) to the test cell assembly 1924, and (iii) an outlet conduit 1956 that receives the sample 12 from the test cell assembly 1925. These components can be used in any of the processing assemblies 10, 180, 910, 1010 described above. As a non-exclusive example, (i) the inlet conduit 1954 can be in fluid communication with the sample delivery system 14 (illustrated in Figure 1 ) to deliver the sample 12 to the test cell 1925; and/or (i) the outlet conduit 1956 can be in fluid communication with the retainer receptacle 18 (illustrated in Figure 1 ) to remove the sample 12 from the test cell 1925.

[00270] As non-exclusive examples, each conduit 1954, 1956 can include a flexible fluid tube, cylindrical tubing, or any other suitable conduit. In Figure 19A, each of the test cell 1925, the inlet conduit 1954, and the outlet conduit 1956 has a circular-shaped crosssection; and the test cell 1925 has an internal test diameter 1960a, the inlet conduit 1954 has an inlet diameter 1954b, and the outlet conduit 1956 has an outlet diameter 1956b. Further, in one, non-exclusive implementation, the test diameter 1960a, the inlet diameter 1954b, and the outlet diameter 1956b are approximately the same.

[00271] In the implementation of Figure 19A, the modular test cell assembly 1924 can be easily and selectively coupled to the conduits 1954, 1956. With this design, the modular test cell assembly 1924 and the test cell 1925 can be easily replaced when it becomes fouled or damaged.

[00272] The design of the test cell assembly 1924 and/or the design of the conduits 1954, 1956 can be varied to achieve easy coupling between these components. In one non-exclusive implementation, (i) the test cell assembly 1924 and the inlet conduit 1954 cooperate to form a first connector assembly 1980 that allows for the easy and selective coupling of the inlet conduit 1954 to the test cell assembly 1924, and (ii) the test cell assembly 1924 and the outlet conduit 1956 cooperate to form a second connector assembly 1982 that allows for the easy and selective coupling of the output conduit 1956 to the test cell assembly 1924.

[00273] The design of each connector assembly 1980, 1982 can be varied. In the nonexclusive of Figure 19A, each connector assembly 1980, 1982 is a tri-clamp design. However, other types of connectors can be utilized. For example, one or both of the connector assemblies 1980, 1982 can be Swagelok-type tube fitting. “Swagelok®” is a registered trademark of the Swagelok Company.

[00274] In Figure 19A, the first connector assembly 1980 includes (i) a first connector component (region) 1980a that is formed on the test cell assembly 1924, (ii) a second connector component (region) 1980b that is formed on the inlet conduit 1954, (iii) a seal 1980c positioned between the connector components 1980a, 1980b, and (iv) a clamp 1980d that urges the connector components 1980a, 1980b together to seal the intersection between these components 1980a, 1980b. In one design, each connector component 1980a, 1980b is angular flange shaped. Further, the clamp 1980d can include a flip latch (not shown) that can be controlled to selectively clamp the inlet conduit 1954 to the test cell assembly 1924.

[00275] Similarly, in Figure 19A, the second connector assembly 1982 includes (i) a first connector component (region) 1982a that is formed on the test cell assembly 1924, (ii) a second connector component (region) 1982b that is formed on the outlet conduit 1956, (iii) a seal 1982c positioned between the connector components 1982a, 1982b, and (iv) a clamp 1982d that urges the connector components 1982a, 1982b together to seal the intersection between these components 1982a, 1982b. In one design, each connector component 1982a, 1982b is angular flange shaped. Further, the clamp 1982d can include a flip latch (not shown) that can be controlled to selectively clamp the outlet conduit 1956 to the test cell assembly 1924.

[00276] The design of the modular test cell assembly 1924 can be varied to achieve ease in inserting and aligning the test cell assembly 1924 into the rest of the processing assembly 1910, and ease of attaching the conduits 1954, 1956.

[00277] In the non-exclusive implementation of Figure 19A, the test cell assembly 1924 includes (i) the test cell 1925, and (ii) a modular cell housing 1984 that retains the test cell 1925, maintains the alignment of the test cell 1925, and selectively connects the test cell 1925 in fluid communication with the inlet conduit 1954 and the outlet conduit 1956. The test cell 1925 can be similar to the designs described in reference to Figures 9A-13, and 17.

[00278] The design of the cell housing 1984 can be varied. In the simplified illustration of Figure 19A, the cell housing 1984 includes (i) a first housing component 1985, (ii) a second housing component 1986, (iii) a housing connector 1987 that fixedly secures the housing components 1985, 1986 together, (iv) a first seal 1988 that secures and seals a first end 1925i of the test cell 1925 to the first housing component 1985; and (v) a second seal 1989 that secures and seals a second end 1925j of the test cell 1925 to the second housing component 1986. The design of each of these components can be varied. [00279] In Figure 19A, the first housing component 1985 is generally tubular shaped and includes (i) a tubular-shaped first section 1985a, (ii) a tubular-shaped second section 1985b, and (iii) a connector wall 1985c that connects the second section 1985b to the first section 1985a. In this design, (i) the first section 1985a defines part of the first connector component 1980a of the first connector assembly 1980; (ii) the first section 1985a is sealed and secured to the first end 1925i of the test cell 1925; and (iii) the second section 1985b has a larger diameter and partly encircles the test cell 1925. Moreover, the first section 1985a can have an inner, first section diameter 1985d that matches (is approximately the same as) the test diameter 1960a to minimize any disruption of the flow of the sample 12.

[00280] Somewhat similarly, in Figure 19A, the second housing component 1986 is generally tubular shaped and includes (i) a tubular-shaped first section 1986a, (ii) a tubular-shaped second section 1986b, and (iii) a connector wall 1986c that connects the second section 1986b to the first section 1986a. In this design, (i) the first section 1986a defines part of the first connector component 1982a of the second connector assembly 1982; (ii) the first section 1986a is sealed and secured to the second end 1925j of the test cell 1925; and (iii) the second section 1986b has a larger diameter and partly encircles the test cell 1925. Moreover, the second section 1986a can have an inner, second section diameter 1986d that matches (is approximately the same as) the test diameter 1960a to minimize any disruption of the flow of the sample 12.

[00281] The housing components 1985, 1986 can be made of plastic or other suitable materials. One or both of the housing components 1985, 1986 can include one or more housing access areas (not shown in Figure 19A) for allowing the incident light beam 928a (shown in Figure 9A) and/or the detector beam 926a (shown in Figure 9A) to pass therethrough to the test cell 1925. In this design, the housing access area(s) are alignable with the access area 925c (illustrated in Figure 9A).

[00282] Furthermore, one or both of the housing components 1985, 1986 can include one or more module alignment features (not shown in Figure 19A) that align the module test cell assembly 924 to the components of the processing assembly 1410, such as the light source assembly 928 (illustrated in Figure 9A) and the detector assembly 926 (illustrated in Figure 9A). [00283] Additionally, one or both of the housing components 1985, 1986 can include one or more test cell aligners (not shown in Figure 19A) that align the test cell 1925 to the housing components 1985, 1986 during assembly of the test cell assembly 1924.

[00284] The housing connector 1987 fixedly secures the housing components 1985, 1986 together with the test cell 1925 therebetween. In non-exclusive example in Figure 19A, the housing connector 1987 is an adhesive (e.g., an epoxy) that fixedly secures the housing components 1985, 1986 together. Alternatively, for example, the housing connector 1987 can include one or more fasteners (not shown) that selectively secure the housing components 1985, 1986 together.

[00285] As provided above, (i) the first seal 1988 secures and seals the first end 1925i of the test cell 1925 to the first housing component 1985, and (ii) the second seal 1989 secures and seals the second end 1925j of the test cell 1925 to the second housing component 1986. For example, each seal 1988, 1989 can be an adhesive (e.g., an epoxy). Alternatively, for example, one or both of the seals 1988, 1989 can include an “O” ring type seal (not shown) and some type of fastener assembly (not shown).

[00286] With this design, for example, the operator of the processing assembly 1910 can have in storage one or more replacement, modular test cell assemblies 1924, with each replacement, modular test cell assemblies 1924 being in a separate bag. When the currently used test cell assembly 1924 becomes fouled, it can be removed from the processing assembly 1910. Next, the replacement test cell assembly 1924 can be (i) removed from the bag, (ii) inserted into the processing assembly 1910, and (iii) properly aligned with the other components of the processing assembly 1910, such as the light source assembly 928 and the detector assembly 926. Finally, the inlet conduit 1954 and the outlet conduit 1956 can be coupled to the modular test cell assembly 1924. Now, the processing assembly 1910 is ready to resume testing.

[00287] Other arrangements of the processing assembly 1910 are possible. For example, the processing assembly 1910 of Figure 19A can be modified somewhat similarly to Figure 11 to include a second test cell assembly (not shown in Figure 19A) and a connector conduit (not shown in Figure 19A) that maintains the separation distance between the test cell assemblies. Further, in this design, the connector conduit may be designed to (i) have a diameter that matches the other components; and (ii) include ends (e.g., flanges) that allow for quick coupling and decoupling to the other components.

[002881 Figure 19B is a simplified side view of a portion of the implementation of the processing assembly 1910 shown in Figure 19A including the test cell 1925, the second housing component 1986, the second connector assembly 1982, and the outlet conduit 1956. In Figure 19B, the inlet conduit 1954 (illustrated in Figure 19A) and other components on the inlet side of the processing assembly 1910 have been removed. As shown in Figure 19B, the second housing component 1986 can include a second housing access area 1986e and one or more housing aligners 1990.

[00289] The second housing access area 1986e (i) allows the light beam 1928a (illustrated in Figure 19C) to pass through the second housing component 1986 and be incident upon the access area 1925c of the test cell 1925, and (ii) allows the detector beam 1926b (illustrated in Figure 19C) exiting from the access area 1925c of the test cell 1925 to pass through the second housing component 1986. Although not shown in Figure 19B, it is appreciated that the first housing component 1985 can include a first housing access area (not shown) that is substantially similar to the second housing access area 1986e. The first housing access area (not shown) and the second housing access area 1986e can be positioned adjacent to each other so that they combine to have a somewhat similar cross-sectional shape as the access area 1925c. As a non-exclusive example, the housing access areas 1986e can each be an opening having a rectangular shape or another configuration. Alternatively, the housing access areas 1986e can be a region (e.g., a window) that is transparent to the wavelengths of the light beam 1928a and the detector beam 1926b. Still alternatively, the housing components 1986 can be designed so that only one of them includes the housing access areas 1986e.

[00290] The one or more housing aligners 1990 can be used to align the first housing component 1985 to the second housing component 1986 during assembly. The housing aligners 1990 illustrated in Figure 19B can align the housing components 1985, 1986 in cooperation with corresponding housing aligners (not shown) and/or aligner receivers (e.g., apertures, not shown) that are included in the first housing component 1985. In nonexclusive, non-limiting embodiments, the housing aligners 1990 can include alignment pins and/or alignment rings. The housing aligners 1990 can vary depending on the design requirements of the processing assembly 1910.

[002911 Figure 19C is a simplified end view of the portion of the implementation of the processing assembly 1910 shown in Figure 19B, including the test cell 1925, and the second housing component 1986 with the housing aligners 1990, and the second housing access area 1986e. In the implementation of Figure 19C, the light source assembly 928 (illustrated in Figure 9A) directs the incident light beam 1928a through the housing access area 1986e in the second housing component 1986 and into the test cell 1925 through the access area 1925c at the first surface 1925a in a fashion so that the light beam 1928a bounces 1929 (each highlighted with a dashed oval) at least once off of the first surface 1925a. In the simplified illustration of Figure 19C, the light beam 1928a bounces six times off of the first surface 1925a, and five times off of the second surface 1925b. Subsequently, after one or more radial bounces 1929, the detector beam 1926a exits the access area 1925c of the test cell 1925 and passes through the first housing access area (not shown), and the second housing access area 1986e.

[00292] Figure 20 is a simplified end view of yet another implementation of a processing assembly 2010 that is substantially similar to the implementation displayed in Figure 19C. One or both of the housing components 1985 (illustrated in Figure 19A), 2086 can further include a test cell aligner 2091 that aligns the test cell 2025 relative to the first housing component (not shown in Figure 20) and/or the second housing component 2086 during assembly. Moreover, the test cell aligner 2091 can properly align the access area 2025c of the test cell 2025 with the housing access areas 2086e during assembly.

[00293] In some embodiments, such as shown in Figure 20, the test cell aligner 2091 can be provided as a plurality of test cell aligners 2091 . As provided hereinto, proper alignment between the test cell 2025 and the housing components 2086, and proper alignment of the access areas 2025c, 2086e allows the light beam 2028a to be incident on the test cell 2025 at the desired angle, and for detector beam 2026b to exit the assembly at the desired angle. Non-limiting, non-exclusive examples of suitable test cell aligners 2091 include (i) alignment balls and/or (ii) flexures positioned between the test cell 2025 and the housing components 2086. [00294] In various implementations, (i) the first housing component 1985 (illustrated in Figure 19A) and/or the second housing component 2086 can additionally each include a module aligner 2092, and (ii) the processing assembly 2010 can include a processing assembly aligner 2093. The module aligner 2092 and the processing assembly aligner 2093 work in cooperation to align the housing components 1985, 2096 to the processing assembly 2010.

[00295] As a non-exclusive example, the module aligner 2092 can include an alignment structure that engages an alignment recess of the processing assembly aligner 2093. In certain implementations, the processing assembly aligner 2093 can include an alignment recess that has a shape that only matches the shape of the alignment structure of the module aligner 2092. The shape matching of the aligners allows for (i) the precise positioning of the housing components 1985, 2096 (with the test cell 2025) relative to the other components (e.g., the detector assembly 26 (illustrated in Figure 1 ) and the light source assembly 28 (illustrated in Figure 1 ) of the processing assembly 2010, and (ii) quick exchange and/or removal of the module with the test cell 2025 from the processing assembly 2010. The module aligner 2092 and the processing assembly aligner 2093 can vary depending on the requirements of the processing assembly 2010.

[00296] While the particular systems as shown and disclosed herein are fully capable of obtaining the objects and providing the advantages herein before stated, it is to be understood that it is merely illustrative of the presently preferred embodiments of the invention and that no limitations are intended to the details of construction or design herein shown other than as described in the appended claims.

Claims

What is claimed is:

1 . A test cell assembly for receiving a sample that is analyzed with an incident light beam, the test cell assembly comprising: a test cell including an attenuated total reflector having a curved first surface that defines at least a portion of a test internal channel for receiving the sample, a second surface that is spaced apart from the curved first surface, and an access area for receiving the incident light beam that is directed at the first surface.

2. The test cell assembly of claim 1 wherein the attenuated total reflector is annular-shaped.

3. The test cell assembly of claim 1 wherein the attenuated total reflector is hollow cylindrical shaped, the second surface is curved, and the second surface is substantially coaxial with the first surface.

4. The test cell assembly of claim 1 wherein the attenuated total reflector includes an arch-shaped region.

5. The test cell assembly of claim 1 wherein at least one of the surfaces has an index of refraction of greater than approximately 1.35.

6. The test cell assembly of claim 1 wherein the access area is on the second surface, and wherein the incident light beam has an incidence angle on the first surface of between approximately twenty and fifty degrees.

7. The test cell assembly of claim 6 wherein the access area is configured to allow the light beam to exit the attenuated total reflector.

8. The test cell assembly of claim 7 wherein the access area includes a first access region and a second access region; wherein the incident light beam passes through the first access region, and wherein the light beam exits from the test cell from the second access region.

9. The test cell assembly of claim 1 wherein the access area includes at least one of an aperture, a flat, a notch, and a groove.

10. The test cell assembly of claim 1 wherein the surfaces are configured so that (i) the light beam strikes the curved first surface at an incidence angle greater than a critical angle of the curved first surface, and (ii) the light beam propagates between the surfaces with successive reflections between the curved first surface and the second surface.

11. The test cell assembly of claim 10 wherein the light beam propagates between the curved first surface and the second surface for at least five bounces.

12. The test cell assembly of claim 10 wherein the light beam propagates between the curved first surface and the second surface in one of (i) a clockwise direction, and (ii) a counterclockwise direction relative to a central axis of the test internal channel.

13. The test cell assembly of claim 10 wherein the light beam reflects between the curved first surface and the second surface in a helical manner relative to a central axis of the test internal channel.

14. The test cell assembly of claim 1 wherein the curved first surface includes a film that includes at least one of the following characteristics (i) improves the chemical stability of the curved first surface, (ii) inhibits binding of biological materials to the curved first surface, (iii) at least partially hydrophilic, and (iv) at least partially hydrophobic.

15. An assembly including the test cell assembly of claim 1 , and an inlet conduit having an inlet channel that is adapted to receive the sample, the inlet channel having an inlet cross-sectional area and an inlet cross-sectional shape; wherein the test internal channel is in fluid communication with the inlet channel so that the sample moves from the inlet channel to the test internal channel, wherein the test internal channel has a test cross-sectional area that is approximately equal to the inlet cross-sectional area, and a test cross-sectional shape that is approximately equal to the inlet cross-sectional shape.

16. The assembly of claim 15 further comprising an outlet conduit having an outlet channel that is adapted to receive the sample, the outlet channel having an outlet cross-sectional area and an outlet cross-sectional shape, wherein the test internal channel is in fluid communication with the outlet channel so that the sample moves from the inlet channel to the test internal channel to the outlet channel, wherein the test cross- sectional area is approximately equal to the outlet cross-sectional area, and the test cross-sectional shape is approximately equal to the outlet cross-sectional shape.

17. The assembly of claim 16 wherein the inlet channel has a circular cross- sectional shape, the outlet channel has a circular cross-sectional shape, and the test internal channel has a circular cross-sectional shape.

18. The assembly of claim 17 wherein the inlet channel has an inlet diameter, the outlet channel has an outlet diameter, and the test internal channel has a test diameter, and wherein the test diameter is approximately equal to at least one of the inlet diameter and the outlet diameter.

19. An assembly including the test cell assembly of claim 1 and a light source assembly that directs the incident light beam through the access area at the first surface with the light beam having an incidence angle of greater than a critical angle of the test cell.

20. The assembly of claim 19 wherein the incident light beam has parallel polarization.

21 . The assembly of claim 19 wherein the incident light beam is converging.

22. The assembly of claim 21 wherein the incident light beam has a virtual focal point that is located within the test internal channel.

23. The assembly of claim 21 wherein the incident light beam satisfies a 4-f Fourier optical system.

24. The assembly including the test cell assembly of claim 1 , an inlet conduit that directs the sample to the test cell, and an outlet conduit that receives the sample from the test cell; wherein test cell assembly includes a cell housing that retains the test cell; wherein the cell housing includes (i) a first connector component that selectively couples the cell housing to the inlet conduit with the inlet conduit being in fluid communication with the test cell, and (ii) a second connector component that selectively couples the cell housing to the outlet conduit with the outlet conduit being in fluid communication with the test cell.

25. The assembly of claim 24 wherein the test cell is positioned between the first connector component and the second connector component

26. The assembly of claim 24 wherein the cell housing includes a housing optical access area that is alignable with the access area so that incident light beam can be directed at the first surface through the cell housing.

27. The assembly of claim 24 wherein the cell housing includes a test cell aligner that aligns the test cell with the cell housing.

28. The assembly of claim 19 further comprising a detector that receives the light beam from the test cell and generates detector data; and (iv) a control-and-analysis system that uses the detector data to analyze the sample.

29. A fluid analyzer for analyzing a sample, the fluid analyzer comprising: a test cell assembly that receives the sample, the test cell assembly including an attenuated total reflector that contacts the sample, the attenuated total reflector including a first ATR region and a second ATR region that is spaced apart from the first ATR region; a light source assembly that directs a first light beam into the first ATR region that is reflected within the first ATR region; and a second light beam into the second ATR region that is reflected within the second ATR region; a first detector that generates a first data signal that corresponds to the light reflected within the first ATR region; a second detector that generates a second data signal that corresponds to the light reflected within the first ATR region; and a control system that uses the first data signal and the second data signal to analyze the flowing sample.

30. The sample analyzer of claim 29 wherein a first beam center wavelength of the first light beam is approximately equal to a second beam center wavelength of the second light beam.

31 . The sample analyzer of claim 30 wherein the first beam center wavelength is changed over time as the sample moves in the test cell assembly, and wherein the second beam center wavelength is changed over time as the sample moves in the test cell assembly.

32. The sample analyzer of claim 29 wherein the attenuated total reflector is tubular shaped.

33. The sample analyzer of claim 29 wherein the attenuated total reflector is trapezoidal-prism shaped.

34. A test cell assembly for receiving a sample that is analyzed with an incident light beam, the test cell assembly comprising: an inlet conduit having an inlet channel that is adapted to receive the sample, the inlet channel having an inlet cross-sectional area and an inlet cross- sectional shape; and a test cell that defines a test internal channel that is in fluid communication with the inlet channel so that the sample moves from the inlet channel to the test internal channel, the test cell including an attenuated total reflector that contacts the sample, the attenuated total reflector including an access area for receiving the light beam so that the light beam internally reflects within the attenuated total reflector, and wherein the test internal channel has a test cross-sectional area that is approximately equal to the inlet cross-sectional area, and a test cross-sectional shape that is approximately equal to the inlet cross-sectional shape.

35. The test cell assembly of claim 34 further comprising an outlet conduit having an outlet channel that is adapted to receive the sample that moves from the test internal channel, the outlet channel having an outlet cross-sectional area that is approximately equal to the test cross-sectional area, and an outlet cross-sectional shape that is approximately equal to the test cross-sectional shape.

36. The test cell assembly of claim 35 further comprising a seal that is configured to seal a junction between the test cell and at least one of the conduits.

37. The assembly of claim 35 wherein the inlet channel has a circular cross- sectional shape, the outlet channel has a circular cross-sectional shape, and the test internal channel has a circular cross-sectional shape.

38. The assembly of claim 37 wherein the inlet channel has an inlet diameter, the outlet channel has an outlet diameter, and the test internal channel has a test diameter, and wherein the test diameter is approximately equal to at least one of the inlet diameter and the outlet diameter.

39. A method for analyzing a sample with an incident light beam comprising: positioning the sample in a test cell including a total attenuated reflector having a curved first surface that defines at least a portion of a test internal channel that receives the sample, a second surface that is spaced apart from the first surface, and an access area for receiving the incident light beam that is reflected within the reflection crystal.

40. The method of claim 39 wherein the attenuated total reflector is annularshaped.

41 . The method of claim 39 wherein the attenuated total reflector is hollow cylindrical shaped, the second surface is curved, and the second surface is substantially coaxial with the first surface.

42. The method of claim 39 wherein the attenuated total reflector includes an arch-shaped region.

43. The method of claim 39 wherein at least one of the surfaces has an index of refraction of greater than approximately 1 .35.

44. The method of claim 39 wherein the access area is on the second surface, and wherein the incident light beam has an incidence angle on the first surface of between approximately twenty and fifty degrees.

45. The method of claim 44 wherein the access area is configured to allow the light beam to exit the attenuated total reflector.

46. The method of claim 45 wherein the access area includes a first access region and a second access region; wherein the incident light beam passes through the first access region, and wherein the light beam exits from the test cell from the second access region.

47. The method of claim 39 wherein the access area includes at least one of an aperture, a flat, a notch, and a groove.

48. The method of claim 39 wherein the surfaces are configured so that (i) the light beam strikes the curved first surface at an incidence angle greater than a critical angle of the curved first surface, and (ii) the light beam propagates between the surfaces with successive reflections between the curved first surface and the second surface.

49. The method of claim 48 wherein the light beam propagates between the curved first surface and the second surface for at least five bounces.

50. The method of claim 48 wherein the light beam propagates between the curved first surface and the second surface in one of (i) a clockwise direction, and (ii) a counterclockwise direction relative to a central axis of the test internal channel.

51 . The method of claim 48 wherein the light beam reflects between the curved first surface and the second surface in a helical manner relative to a central axis of the test internal channel.

52. The method of claim 39 wherein the curved first surface includes a film that includes at least one of the following characteristics (i) improves the chemical stability of the curved first surface, (ii) inhibits binding of biological materials to the curved first surface, (iii) at least partially hydrophilic, and (iv) at least partially hydrophobic.

53. A method for analyzing a sample with an incident light beam comprising: positioning the sample in a test cell assembly including the test cell of claim

1 and an inlet conduit having an inlet channel that is adapted to receive the sample, the inlet channel having an inlet cross-sectional area and an inlet cross-sectional shape; wherein the test internal channel is in fluid communication with the inlet channel so that the sample moves from the inlet channel to the test internal channel, wherein the test internal channel has a test cross-sectional area that is approximately equal to the inlet cross-sectional area, and a test cross-sectional shape that is approximately equal to the inlet cross-sectional shape.

54. The method of claim 53 wherein the test cell assembly further includes an outlet conduit having an outlet channel that is adapted to receive the sample, the outlet channel having an outlet cross-sectional area and an outlet cross-sectional shape, wherein the test internal channel is in fluid communication with the outlet channel so that the sample moves from the inlet channel to the test internal channel to the outlet channel, wherein the test cross-sectional area is approximately equal to the outlet cross-sectional area, and the test cross-sectional shape is approximately equal to the outlet cross- sectional shape.

55. The method of claim 54 wherein the inlet channel has a circular cross- sectional shape, the outlet channel has a circular cross-sectional shape, and the test internal channel has a circular cross-sectional shape.

56. The assembly of claim 55 wherein the inlet channel has an inlet diameter, the outlet channel has an outlet diameter, and the test internal channel has a test diameter, and wherein the test diameter is approximately equal to at least one of the inlet diameter and the outlet diameter.

57. The method of claim 53 further comprising the step of directing the incident light beam through the access area at the first surface with the light beam having an incidence angle of greater than a critical angle of the test cell with a light source assembly.

58. The method of claim 57 wherein the incident light beam has parallel polarization.

59. The assembly of claim 57 wherein the incident light beam is converging.

60. The assembly of claim 59 wherein the incident light beam has a virtual focal point that is located within the test internal channel.

61 . The assembly of claim 59 wherein the incident light beam satisfies a 4-f Fourier optical system.

62. A fluid analyzer for analyzing a sample, the fluid analyzer comprising: a test cell assembly that receives the sample, the test cell assembly including an attenuated total reflector that contacts the sample, the attenuated total reflector including a first ATR region and a second ATR region that is spaced apart from the first ATR region; and a light source assembly that directs a first light beam into the first ATR region that is reflected within the first ATR region; and a second light beam into the second ATR region that is reflected within the second ATR region.

63. The fluid analyzer of claim 62 wherein the first ATR region is at least partly positioned in the first test cell and the second ATR region is at least partly positioned in the second test cell.

64. The fluid analyzer of claim 62 wherein the first ATR region and the second ATR region are positioned on opposite sides of an ATR central axis of the attenuated total reflector.

65. The fluid analyzer of claim 62 further comprising a detector that generates data that corresponds to the light reflected within the ATR regions.

66. The fluid analyzer of claim 65 wherein the attenuated total reflector includes (i) a first reflector surface, (ii) a second reflector surface that is spaced apart from the first reflector surface, (iii) an angled, first end facet for receiving the light beams into the attenuated total reflector, and (iv) an angled, second end facet for allowing light to exit the attenuated total reflector.

67. The fluid analyzer of claim 66 wherein (i) the first light beam enters through the first end facet and is incident on the second reflector surface in the first ATR region, and (ii) the second light beam enters through the first end facet and is incident on the second reflector surface in the second ATR region.

68. The fluid analyzer of claim 67 wherein (i) the first light beam reflects between the reflector surfaces in the first ATR region before exiting the second end facet as a first detector beam, and (ii) the second light beam reflects between the reflector surfaces in the second ATR region before exiting the second end facet as a second detector beam.

69. The fluid analyzer of claim 68 wherein the detector receives the first detector beam and the second detector beam.

70. The fluid analyzer of claim 62 wherein the first light beam interrogates the sample in the first ATR region and the second light beam interrogates the sample in the second ATR region.

71. A fluid analyzer for analyzing a flowing sample, the fluid analyzer comprising: a flow cell assembly that receives the flowing sample, the flow cell assembly having a first location and a second location that is spaced apart from the first location; a detector assembly that generates a first data that corresponds a characteristic of the sample at the first location, and a second data that corresponds to a characteristic of the sample at the second location; and a control system that uses the first data and the second data to analyze the flowing sample.