Patent Publication Number: US-2010125041-A1

Title: Methods of testing a plurality of test samples and systems therefor

Description:
CROSS-REFERENCE TO RELATED APPLICATION(S) 
     This application claims benefit of priority from U.S. Provisional Patent Application No. 61/114,488, filed Nov. 14, 2008, which application is incorporated by reference herein in its entirety. 
    
    
     FIELD OF INVENTION 
     The invention relates generally to methods and systems for testing a plurality of test samples in parallel and in particular to methods of testing physicochemical property of the plurality of test samples. 
     BACKGROUND 
     Combinatorial chemistry is a relatively new area of research aimed at rapid synthesis and testing methods to build libraries of polymeric, organic, inorganic or solid state materials. The term “combinatorial chemistry” generally refers to methods and materials for creating collections of diverse materials or compounds commonly known as libraries and to techniques and instruments for evaluating or screening libraries for desirable properties. For example, combinatorial chemistry techniques with the aid of high throughput systems have empowered chemists to rapidly produce large libraries of discrete molecules in the pursuit of discovery of new materials or materials with desirable properties thus reducing the time frame of these discoveries. Consequently, the discovery of new materials with novel chemical and physical properties can depend largely on the ability to analyze the new materials in parallel. 
     The new materials can have wide ranging applications in industry namely, transportation, housing, personal care, fabric and surface care, agrochemicals and food packaging. Certain applications may require the new material to be formed as films. Some of these applications may require the films to provide resistance to external environment. Certain other applications may require the film to dissolve and/or disintegrate after a period of time. The physicochemical properties of the films such as compatibility with other materials have to be tested for their possible utility in these applications. Some of the currently practiced techniques are ASTM standard testing methods such as ASTM Standard D5402-06 or ASTM D870-02. 
     ASTM Standard D5402-06, “Standard Practice for Assessing the Solvent Resistance of Organic Coatings Using Solvent Rubs”, ASTM International, West Conshohocken, Pa. involves a solvent rub technique for assessing the solvent resistance of an organic coating that chemically changes during the curing process. The solvent resistance is assessed by visual observation. Moreover, this technique may not be suitable for testing plurality of films in parallel. ASTM D870-02 “Standard Practice for Testing Water Resistance of Coatings Using Water Immersion”, ASTM International, West Conshohocken, Pa. involves testing water resistance of coatings by the partial or complete immersion of coated specimens in distilled or de-mineralized water at ambient or elevated temperatures. The resistance to water is assessed by visual examination and it requires large amounts of water. Therefore, it is desirable to provide improved methods and systems for testing plurality of samples in parallel. 
     SUMMARY OF THE INVENTION 
     According to one embodiment of the invention, a method for testing a plurality of test samples in parallel is provided. The method includes providing a test assembly having the plurality of test samples, wherein the plurality of test samples is provided over a plurality of cells in the test assembly. A test fluid, a test object, or both are provided over the plurality of test samples to determine a physicochemical property of the plurality of test samples. The test fluid may be a test liquid or a test gas but is preferably a liquid. The method further includes monitoring a displacement of the plurality of test samples provided over the plurality of cells by a detection system, wherein monitoring the displacement includes monitoring a displacement of the test sample in contact with the test fluid and/or the test object across the plurality of cells. The physicochemical property of the plurality of test samples is determined from the displacement of the plurality of test samples. 
     In another embodiment, a system for testing a plurality of test samples in parallel is provided. The system includes a test assembly having the plurality of test samples, wherein the plurality of test samples is provided over a plurality of cells within the test assembly. The system further includes a test fluid, a test object, or both a test fluid and test object over the plurality of test samples to test a physicochemical property of the plurality of test samples. The system further includes a detection system to monitor a displacement of the plurality of test samples provided over the plurality of test samples, wherein the detection system further monitors a displacement of the test sample in contact with the test fluid and/or the test object across the plurality of cells. 
    
    
     
       DRAWINGS 
       These and other features, aspects, and advantages of the present invention will become better understood when the following detailed description is read with reference to the accompanying drawings in which like characters represent like parts throughout the drawings, wherein: 
         FIGS. 1-3  illustrate fabrication stages of a test assembly, in accordance with embodiments of the present invention; 
         FIGS. 4-8  illustrate fabrication stages of a test assembly, in accordance with embodiments of the present invention; and 
         FIG. 9  is a schematic representation of a system for testing a plurality of test samples in parallel, according to embodiments of the present invention. 
     
    
    
     DETAILED DESCRIPTION 
     As used herein, the term “test” refers to relative screening of the plurality of test samples whereby the property of the plurality of test samples is determined relative to each other. In some embodiments, the property of the plurality of test samples can be determined with reference to at least one sample of known property. The term “test” as used herein also refers to determining individual property of each of the plurality of test samples. 
     A test assembly having the plurality of test samples is provided. In some embodiments, the test assembly forms part of a high throughput system for screening large libraries of materials in parallel. The plurality of test samples is provided over a plurality of cells within the test assembly. In some embodiments, the plurality of test samples is a film. In some embodiments, the plurality of test samples is a multi-layered film having more than one film layer. For example, the plurality of test samples can be a laminate, for use in packaging industry, composed of two film layers attached to each other by means of an adhesive layer. In certain embodiments, each of the plurality of test samples can be of same kind of film. The same kind of film can have similar chemical composition, or mechanical properties such as thickness; or physical properties such as optical properties. As will be appreciated, the plurality of test samples can be composed of inorganic materials, organic materials, polymeric materials or any combinations thereof. In some embodiments, each of the plurality of test samples is composed of water-soluble polymers, bio-degradable polymers, polyvinyl alcohols, latex films, cellulosics, waxes, or even compressed powders. In one example, each of the plurality of test samples is made of polyvinyl chloride (PVC). In certain other embodiments, each of the plurality of test samples can be of different kinds of films. For example, each of the plurality of test samples can be made of a polymeric blend of PVC and polyketone having a composition, wherein a ratio of PVC to polyketone in the composition varies from one test sample to the other. In some embodiments, at least one of the plurality of test samples is composed of a polymeric material and has a coating to enhance a property of the film, for example a barrier property. 
     Without any limitation, the plurality of test samples can be rigid or flexible. The plurality of test samples can be transparent, translucent or opaque. As used herein, the terms “transparent”, “translucent” or “opaque” refers to the light transmission ability of the plurality of test samples. As used herein, the term “light” refers to electromagnetic radiation in a range of frequencies running from infrared through the ultraviolet, roughly corresponding to a range of wavelengths from about 1 nanometer (10 −9  meters) to about 100 microns (10 −4  meters). 
     The plurality of test samples can be of any suitable shape and/or size. For example, the shape of the plurality of test samples can be similar to the shape of the plurality of cells. In one example, the plurality of test samples can have a dimension that is about or greater than about an opening of the plurality of cells. In some embodiments, the plurality of test samples can have a thickness in the range of about 0.025 millimeters (mm) to about 5.0 mm in thickness. In one embodiment, the plurality of test samples can have a thickness in the range of about 0.1 mm to about 1.0 mm in thickness. 
     A test fluid, a test object, or both are provided over the plurality of test samples. In some embodiments, the test fluid is provided by means of automated lines operable to provide the test fluid over the plurality of test samples. In certain embodiments, the test fluid and/or the test object can be provided manually. This step is preferably performed in a parallel manner. For example, one may provide the test fluid and/or the test object in a row by row manner over the plurality of test samples, or by simultaneously providing over all of the plurality of test samples. 
     In some embodiments, the test fluid can be a gas or liquid but is preferably a liquid such as solvent; slurrie; paste; gel or any combination thereof. Exemplary test liquids include water, hydrocarbon solvents, methanol, ethanol, propanol, methyl ethyl ketones, glycol ethers, mineral oils, hexane, octane and any combinations thereof. In one embodiment, the test liquid is buffered aqueous solution or buffered salt solution or any combinations thereof. In some embodiments, the test fluid provided over the plurality of test samples is of the same kind. In certain embodiments, the test fluid provided over the plurality of test samples is of different kind. In one example, the test liquid is water and the plurality of test samples is a film composed of a water soluble polymer having a composition, wherein the composition varies from one test sample to the other. In addition the test fluids can be mixed during the course of the experiment using standard mechanical agitation methods such as overhead mixing, magnetic mixing, or laboratory plate shakers. 
     In some embodiments, the test object is a solid of a regular shape or of an irregular shape. In certain embodiments, the test object can be hollow inside having a regular shape or an irregular shape. Exemplary regular shapes include cubes, rods, rectangles, spheres, spirals, and hexagons. Exemplary irregular shapes include distorted regular shapes, for example a distorted cube. 
     In certain embodiments, a contrast agent can be provided over the plurality of test samples. As will be appreciated, the contrast agent can provide clarity while imaging using an optical detection system. In some embodiments, the contrast agent includes dyes, colorants, pigments or any combinations thereof. In one example the contrast agent is a dye that is soluble in the test liquid. Exemplary dyes include acid dyes, basic dyes, anionic dyes, natural dyes and fluorescent dyes such as rhodamine dyes and fluorescein dyes. It is also possible to envisage the use of contrast agents that may provide improvement for non-optical detection systems. 
     In some embodiments, testing the plurality of test samples includes determining a physicochemical property of the plurality of test samples. As used herein, the term “physicochemical property” refers to the chemical, physical and/or mechanical properties of the plurality of test samples. In some embodiments, the physicochemical property of the plurality of test samples of the same kind due to contact with test fluids of different kinds can be utilized for screening the plurality of test fluids and/or the test samples. The physicochemical property of the test samples can be measured as a function of time and/or temperature. In one embodiment, the plurality of test samples can be made to contact the test liquid for a period of time and the physicochemical property of the plurality of test samples over a period of time after removal of the test liquid can be monitored to determine the physicochemical property. Exemplary physicochemical property includes deformation, compatibility, dissolution, stretchability, elongation, dissolution and/or rupture of the plurality of test samples in contact with the test fluid and/or the test object. In one embodiment, the stretchability of the plurality of test samples due to contact with the test liquid is determined by applying a pressure on the plurality of test samples. In one embodiment, such pressure is exerted by means of the test object. 
     A displacement of the plurality of test samples is monitored. In some embodiments, monitoring the displacement of the plurality of test samples includes monitoring the displacement of the plurality of test samples across the plurality of cells using a detection system. The term “displacement” as used herein refers to the change in position of a part or whole of the plurality of test samples. In some embodiments, monitoring the displacement of the plurality of test samples includes monitoring the displacement of the test fluid and/or the test object provided over the plurality of test samples. 
     In one embodiment, the detection system includes a pressure sensing device, a pressure transducer, an optical detection system, an optical scanner, a video camera or any combinations thereof. As will be appreciated, the pressure sensing device can be provided adjoining the plurality of test samples and is operable to monitor the displacement of the plurality of test samples provided over the plurality of cells. In some embodiments, a pressure transducer can be used to monitor the displacement. The pressure transducer can be connected to a pressure line in communication with the plurality of cells below each of the plurality of test samples. The test fluid can be provided over the plurality of test samples. In one embodiment, an initial pressure can be provided by introducing a gas in the plurality of cells and the pressure can be monitored by the pressure transducer. In one example, the pressure transducer may record a lowering of pressure from the initial pressure when the test sample is ruptured. In one embodiment, the pressure transducer may record a lower pressure for a test sample that is ruptured when compared to a test sample that is not ruptured. 
     In one embodiment, a stretchable membrane can be fitted above each of the plurality of test samples. A gas can be injected in a space between the membrane and the plurality of test samples to form a bubble out of the membrane over the plurality of test samples. A displacement of the membrane, due to displacement of the plurality of test samples in contact with the test fluid and/or the test object can be monitored. For example, dissolution of the plurality of test samples may rupture the membranes which can be monitored by an optical detection system. In some embodiments, the pressure sensing device can be used to monitor the displacement of the membrane. 
     In one embodiment, the optical detection system can be provided adjacent to the plurality of test samples. In another embodiment, the optical detection system can be provided along a base of the test assembly. In yet another embodiment, the optical detection system can be provided along a side wall of the test assembly to monitor the displacement of the plurality of test samples. 
     The physicochemical property of the plurality of test samples is determined from the displacement of the plurality of test samples. In one embodiment, the detection system is operable to determine the physicochemical property as a function of time. For example, the plurality of test samples can be tested by monitoring the displacement of the plurality of test samples over time and from the displacement over time, the physicochemical property of each of the plurality of test samples can be determined. In some embodiments, the detection system is operable to determine the physicochemical property as a function of time, or temperature or both. 
       FIGS. 1-3  illustrate fabrication stages of a test assembly, in accordance with embodiments of the present invention. A first template  22  and a second template  24  are provided, in  FIG. 1 . The first template  22  includes a first plurality of openings  26  spaced apart from each other and extending through the first template  22 . The first plurality of openings  26  can be in a single row in the first template  22 . In some embodiments, the first template  22  can be a two-dimensional array having plurality of rows of the first plurality of openings  26 . A plurality of cells  28  is provided in the second template  24 . The plurality of cells  28  are aligned with the first plurality of openings  26  of the first template  22 . In some embodiments, the plurality of cells  28  can be plurality of wells and forms part of the second template  24 . In certain embodiments, the plurality of cells  28  can be plurality of vials that are removable and are placed in the second template  24 . The plurality of cells  28  has an opening  32  and a base  34 . In some embodiments, the base  34  of the plurality of cells  28  is transparent. In certain embodiments, the plurality of cells  28  and the second template  24  are transparent. In  FIG. 1 , the second template has a base  36  for holding the plurality of cells  28 . In some embodiments, the first template  22  and the second template  24  include grooves  38  and  40 , respectively for attaching each other, as discussed later. 
     A test substrate  42  is provided between the first template  22  and the second template  24 , in  FIG. 2 . The test substrate  42  is a film, in some embodiments. The test substrate  42  can be a continuous film or a discontinuous film. The discontinuous film can be cut-outs of the continuous film placed over and aligned with the openings of the plurality of cells  28  of the second template  24 . In some embodiments, the test substrate  42  is of same kind of film having similar chemical composition, or mechanical properties such as thickness; or physical properties such as optical properties. In certain embodiments, the test substrate  42  is of different kinds of films having differing chemical composition, or mechanical properties such as thickness; or physical properties such as optical properties. In the illustrated embodiment of  FIG. 2 , the test substrate  42  is a continuous film. The test substrate  42  forms the plurality of test samples  44 , corresponding to, and aligned with the first plurality of openings  26  of the first template  22  and the plurality of cells  28  of the second template  24 . 
     A sealing element  46  is provided above and/or below the plurality of test samples  44  and between the first template  22  and the second template  24 . As will be appreciated, the sealing element  46  may hold the plurality of test samples  44  in place and may advantageously minimize cross-contamination between the plurality of test samples  44 . In the illustrated embodiment of  FIG. 2  the sealing element  46  is an O-ring. 
     The first template  22  and the second template  24  are attached to form the test assembly  48 , in  FIG. 3 . In one embodiment, the attaching is by mechanical means such as by utilizing a fastener  49  through the grooves  38  and  40  of the first template  22  and the second template  24 , respectively. In some embodiments, the first template  22  and the second template  24  can be attached by means of an adhesive. 
       FIGS. 4-8  illustrate fabrication stages of another test assembly, in accordance with embodiments of the present invention. A first template  50  and a second template  52  are provided, in  FIG. 4 . The first template  50  can be similar to the first template  22  of  FIGS. 1-3 . The first template  50  includes a first plurality of openings  54 . A second plurality of openings  56  is provided in the second template  52 . The second plurality of openings  56  is aligned with the first plurality of openings  26  of the first template  50 . The second plurality of openings  56  can be in a single row in the second template  52 . In some embodiments, the second template  52  can be a two-dimensional array having plurality of rows of the second plurality of openings  56 . In some embodiments, the first template  50  and the second template  52  include grooves  58  and  60 , respectively for attaching to each other. 
     A test substrate  62  is provided between the first template  50  and the second template  52 , in  FIG. 5 . The test substrate  62  can be similar to the test substrate  42  of  FIGS. 2-3 . The test substrate  62  forms the plurality of test samples  64 , corresponding to, and aligned with the first plurality of openings  54  of the first template  50  and the second plurality of openings  56  of the second template  52 . 
     The first template  50  and the second template  52  are attached to form a substrate holder  66 , in  FIG. 6 . A third template  68  having a plurality of cells  70  is provided in  FIG. 7 . The plurality of cells  70  can be similar to the plurality of cells  28  of  FIGS. 1-3 . The plurality of cells  70  has an opening  72  and a base  74 . The base  74  of the plurality of cells  70  can be transparent. In the illustrated embodiment of  FIG. 7 , the plurality of cells  70  extends above an upper surface  76  of the third template  68 . The substrate holder  66  is provided over the third template  68 , in  FIG. 8 . The plurality of test samples  64  are provided over, and aligned with the opening  72  of the plurality of cells  70  of the third template  68  to form a test assembly  78 . In some embodiments, the substrate holder  66  is placed over the third template  68  to form the test assembly  78 . In certain embodiments, the substrate holder  66  is attached to the third template  68  to form the test assembly  78 . 
       FIG. 9  is a schematic representation of a system  80  for testing a plurality of test samples  82  in parallel, according to embodiments of the present invention. The system  80  includes a test assembly  84  and an optical detection system  86 . 
     The test assembly can be fabricated using methods as described previously with reference to  FIGS. 1-8 . The test assembly  84  can include a first template  88  and a second template  90 . The first template  88  has a first plurality of openings  92  spaced apart from each other and extending through the first template  88 . The second template  90  includes a plurality of cells  94  over which the plurality of test samples  82  are provided. A test liquid  96  and a test object  98  are provided over the plurality of test samples  82 . In the illustrated embodiment, the test object  98  is a rod. 
     In  FIG. 9 , the optical detection system  86  is provided below the test assembly  84 . However, the optical detection system  86  can be provided along a side wall  100  of the plurality of cells  34 . The optical detection system  86  can monitor a displacement of the plurality of test samples  82  upon contact with the test liquid  96  and/or the test object  98 . In one embodiment, the optical detection system  86  is operable to simultaneously test all of the plurality of test samples  82 . In certain embodiments, the optical detection system  26  can test the plurality of test samples  82  in a row by row manner. 
     While only certain features of the invention have been illustrated and described herein, many modifications and changes will occur to those skilled in the art. It is, therefore, to be understood that the appended claims are intended to cover all such modifications and changes as fall within the true spirit of the invention.