WO2008044779A1 - Structure micro-pixélisée de dosage de liquide, structure précurseur micro-pixélisée de dosage de liquide, et procédés liés à la fabrication et à la réalisation - Google Patents

Structure micro-pixélisée de dosage de liquide, structure précurseur micro-pixélisée de dosage de liquide, et procédés liés à la fabrication et à la réalisation Download PDF

Info

Publication number
WO2008044779A1
WO2008044779A1 PCT/JP2007/070021 JP2007070021W WO2008044779A1 WO 2008044779 A1 WO2008044779 A1 WO 2008044779A1 JP 2007070021 W JP2007070021 W JP 2007070021W WO 2008044779 A1 WO2008044779 A1 WO 2008044779A1
Authority
WO
WIPO (PCT)
Prior art keywords
assay
pixel
micro
digitally
creating
Prior art date
Application number
PCT/JP2007/070021
Other languages
English (en)
Inventor
John W. Hartzell
Pooran C. Joshi
Paul J. Schuele
Andrei Gindilis
Original Assignee
Sharp Kabushiki Kaisha
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US11/827,176 external-priority patent/US8232108B2/en
Priority claimed from US11/827,335 external-priority patent/US8236245B2/en
Priority claimed from US11/827,175 external-priority patent/US8236571B2/en
Priority claimed from US11/827,174 external-priority patent/US8231831B2/en
Priority claimed from US11/888,491 external-priority patent/US8232109B2/en
Application filed by Sharp Kabushiki Kaisha filed Critical Sharp Kabushiki Kaisha
Publication of WO2008044779A1 publication Critical patent/WO2008044779A1/fr

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0636—Integrated biosensor, microarrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0645—Electrodes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0819—Microarrays; Biochips
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0877—Flow chambers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/18—Means for temperature control
    • B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
    • B01L2300/1822—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks using Peltier elements
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/18—Means for temperature control
    • B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
    • B01L2300/1827—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks using resistive heater
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502707—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the manufacture of the container or its components

Definitions

  • This invention relates to a pixelated, fluid-assay, precursor structure, and a pixelated, fluid-assay structure, and also relates to making methods of such a precursor micro-structure and a micro-structure, and a performance of fluid-material assay.
  • This invention concerns a pixelated, thin-film-based, fluid-assay, active-matrix structure, and more particularly to a row-and-column micro-structure of active, individually digitally-addressable pixels which have been prepared on a supporting substrate as "blank slates" for later, selective, assay-specific, assay-site functionalization, also referred to interchangeably as pixel functionalization, to enable the performance of at least one kind of a fluid-material assay.
  • This invention also concerns a method for producing a pixelated, thin-film-based, fluid-assay, precursor, active-matrix structure, and more particularly to a method for producing a precursor row-and-column micro-structure of active, remotely individually digitally-addressable pixels which have been prepared on a supporting substrate as "blank slates" (shortly to be described) for later, selective, assay-specific, assay-site functionalization to enable the performance of at least one kind of a fluid-material assay.
  • This invention also concerns the field of fluid-material assays, and especially to a significantly improved assay-response , thin-film-based pixel matrix which offers a very high degree of controlled, assay-response, pixel-specific sensitivity with respect to which an assay response (a) can be output-read on a precision, pixel-by-pixel basis, and (b) can additionally be examined along uniquely accessible, special, plural and freely selectable, independent-variable
  • information-gathering axes such as a time-sampling axis, and an electromagnetic-field-variable (light, heat, non-uniform electrical) axis.
  • This invention also concerns a method for producing a pixelated, thin-film-based, fluid-assay, active-matrix structure . More particularly, it pertains to a method for producing a row-and-column micro-structure array of active, remotely individually digitally-addressable pixels which have been prepared on a supporting substrate, each with (a) an included assay sensor (at least one) possessing an assay site (at least one) , and (b) an also included digitally-addressable, electromagnetic field-creating structure.
  • This field-creating structure is energizable to bathe the associated pixel with an ambient electromagnetic field which is one or more of a field of light, a field of heat, and a non-uniform electrical field.
  • the pixels' respective assay sites are functionalized to possess respective assay-material-specificity so as each to have a defined, specific affinity for at least one kind of a fluid-assay material.
  • This invention also concerns the field of fluid-material assays. More particularly, it relates to the performance of such an assay in the specific context of employing a significantly improved type of thin-film-based, active-pixel, pixelated assay-response matrix for "Micro-Pixelated Fluid-Assay Structure".
  • the invention preferably takes the form of a relatively inexpensive , consumer-level-affordable, thin-film-based assay structure which features a low-cost substrate that will readily accommodate low-cost, and preferably "low-temperature-condition” , fabrication thereon of substrate- supported matrix-pixel “components", and a method of creating such a precursor assay structure .
  • Low temperature is defined herein as a being a characteristic of processing that can be done on substrate material having a transition temperature (Tg) which is less than about 850°C , i. e . , less than a temperature which, if maintained during sustained material processing, would cause the subject material to lose dimensional stability.
  • the preferred supporting substrate material is one made of lower-expense glass or plastic materials.
  • glass and plastic employed herein to describe a preferred substrate material should be understood to be referring also to other suitable "low-temperature materials
  • Such substrate materials while importantly contributing on one level to relatively low, overall, end-product cost, also allow specially for the compatible employment, with respect to the fabrication of supported pixel structure, of processes and methods that are based on amorphous, micro-crystal and polysilicon thin-film-transistor (TFT) technology.
  • TFT thin-film-transistor
  • these substrate materials uniquely accommodate the use of the just-mentioned TFT technology in such a way that electrical, mechanical and electromagnetic field-creating devices - devices that are included variously in the structure of the invention -- can be fabricated simultaneously in a process flow which is consistent with the temperature tolerance of such substrate materials.
  • low-temperature TFT devices are formed through deposition processes that deposit silicon-based (or other-material-based, as mentioned below herein, and as referred to at certain points within this text with the expression "etc.") thin film semiconductor material
  • TFT transistors can be fabricated cheaply with a relatively few number of process steps. Further, thin-film deposition processes permit TFT devices to be formed on alternate substrate materials, such as transparent glass substrates, for use , as an example, in liquid crystal displays.
  • TFT device fabrication may variously involve the use typically of amorphous Si (a-Si) , of micro-crystalline Si, and or of polycrystalline Si formed by low-temperature internal crystalline-structure processing of amorphous Si.
  • a-Si amorphous Si
  • micro-crystalline Si amorphous Si
  • polycrystalline Si formed by low-temperature internal crystalline-structure processing of amorphous Si.
  • the invention preferably takes the form of a method for creating a relatively inexpensive, consumer-level-affordable, thin-film-based, assay structure which features a low-cost substrate that will readily accommodate low-cost, and preferably
  • Low-temperature-condition fabrication thereon of substrate- supported matrix-pixel “components” .
  • Low temperature is defined herein as a being a characteristic of processing that can be done on substrate material having a transition temperature (Tg) which is less than about 850°C, i.e. , less than a temperature which, if maintained during sustained material processing, would cause the subject material to lose dimensional stability.
  • Tg transition temperature
  • the matrix-pixel technology which is involved with practice of the methodology of this invention, if so desired, can be implemented on more costly supporting silicon substrates
  • the preferred supporting substrate material employed in the practice of the invention is one made of lower-expense glass or plastic materials.
  • glass and plastic employed herein to describe a preferred substrate material should be understood to be referring also to other suitable "low-temperature materials.
  • substrate materials while importantly contributing on one level to relatively low, overall, end-product cost, also allow specially for the compatible employment, with respect to the fabrication of supported pixel structure, of processes and methods that are based on amorphous, micro-crystal and polysilicon thin-film-transistor
  • TFT thin film spectroscopy
  • these substrate materials uniquely accommodate the use of the just-mentioned, low-temperature TFT technology in such a way that electrical, mechanical and electromagnetic field-creating devices - devices that are included variously in the structure produced by the invention -- can be fabricated simultaneously in a process flow which is consistent with the temperature tolerance of such substrate materials.
  • low-temperature TFT devices are formed through deposition processes that deposit silicon-based (or other-material-based, as mentioned below herein, and as referred to at certain points within this text with the expression "etc.") thin film semiconductor material
  • TFT transistors can be fabricated cheaply with a relatively few number of process steps. Further, thin-film deposition processes permit TFT devices to be formed on alternate substrate materials, such as transparent glass substrates, for use, as an example, in liquid crystal displays.
  • low-temperature TFT device fabrication may variously involve the use typically of amorphous Si (a-Si) , of micro-crystalline Si, and or of polycrystalline Si formed by low-temperature internal crystalline-structure processing of amorphous Si.
  • a-Si amorphous Si
  • micro-crystalline Si amorphous Si
  • polycrystalline Si formed by low-temperature internal crystalline-structure processing of amorphous Si.
  • the active-pixel matrix which is a digitally accessible and controllable structure linkable to a suitable digital computer, offers a very high degree of controlled, assay-response, pixel-specific sensitivity with respect to which an assay response (a) can be output-read on a precision, pixel-by-pixel basis, and (b) can additionally be examined along uniquely accessible, special, plural and freely selectable, independent-variable "information-gathering axes", such as a time-based axis, and an electromagnetic-field-variable (light, heat, non-uniform electrical) axis.
  • the matrix structure with its included electronically active pixels which structure is preferably employed in the assay-performance practice of the present invention, is formed conveniently on a low-temperature substrate material, such as glass, and may involve, in its underlying construction, low-temperature, internal crystalline-structural processing of a material, such as amorphous silicon, to create some of its pixel-borne structural features.
  • a low-temperature substrate material such as glass
  • Such crystalline-structural processing is described in U . S. Patent No. 7, 125 ,45 1 B2 , the disclosure content of which patent is also hereby incorporated herein by reference.
  • the present invention may be described as a method of performing a fluid-material assay employing an appropriately provided (i. e . , made available) computer-accessible device (note the discussion above) -- preferably a pixelated matrix device, including at least one active digitally-addressable pixel having a sensor with a digitally-addressable assay site functionalized for selected fluid-assay material, with the key steps of this method including, following, of course, providing such a device, exposing the pixel's sensor assay site to such material, and in conjunction with such exposing, and employing the computer-accessible, active nature of the provided device's pixel, remotely and digitally requesting from the pixel's sensor assay site an assay-result output report.
  • an appropriately provided i. e . , made available
  • a computer-accessible device preferably a pixelated matrix device, including at least one active digitally-addressable pixel having a sensor with a digitally-addressable as
  • the basic methodology further includes, in relation to the mentioned employing step, creating, relative to the sensor's assay site in the at least one pixel, a predetermined, pixel-specific electromagnetic field environment.
  • the creation of such an environment is enabled by the type of matrix structure of this invention, and is specifically enabled by the presence in the described matrix pixels of one or several digitally accessible and energizable electromagnetic field-creating structure(s) .
  • Fig. 1 is a simplified, fragmentary, block/ schematic view of a portion of a digitally-addressable, pixelated, fluid-assay, active-matrix micro-structure formed in accordance with a preferred and best mode embodiment of the present invention.
  • Fig. 2 is similar to Fig. 1 , except that it provides a slightly more detailed view of the structure shown in Fig. 1 .
  • Fig. 3 which is prepared on a somewhat larger scale than those scales employed in Fig. 1 and Fig. 2 , illustrates, schematically, different, single, overall, matrix-organizational ways in which precursor fluid-assay pixels in the matrix micro-structure of this invention may be organized, user-selectively, into different functionalized arrangements for different fluid-assays that are ultimately to be performed.
  • Fig. 4 is a fragmentary, block/ schematic diagram illustrating one form of an electromagnetic field-creating structure prepared in accordance with practice of the present invention, and specifically such a structure which is intended to create an ambient, electromagnetic, pixel-bathing field environment characterized by light.
  • Fig. 5 is similar to Fig. 4, except that it illustrates another field-of-light-environment-creating structure.
  • Fig. 6 provides a fragmentary, schematic illustration of one form of a heat-field-creating structure .
  • Fig. 7 illustrates fragmentarily another form of a heat-field-creating structure which has been prepared on the body of a mechanical cantilever beam which also carries an electrical signaling structure that responds to beam deflection to produce a related electrical output signal.
  • Fig. 8 is an isometric view of a pixel-bathing, non-uniform electrical-field-creating structure prepared through a recently developed process, touched upon later in this specification, involving internal crystalline-structure processing of substrate material.
  • Fig. 9 provides a simplified side elevation of the structure presented in Fig. 8 , schematically picturing, also, a pixel-bathing, non-uniform electrical field.
  • Figs. 1 OA, 1 OB and 1 OC illustrate, in greatly simplified forms, three different kinds of three-dimensional spike features which may be created in relation to what is shown generally in Fig. 8 and Fig. 9 for the production of a non-uniform electrical field.
  • Fig 1 1 provides a fragmentary view, somewhat like that presented in Fig. 1 , but here showing a pixel which has been created in accordance with practice of the present invention to include two (plural) assay sensors, each of which is designed to receive and host a single, potential fluid-material assay site.
  • Fig. 12 is somewhat similar to Fig. 1 1 , except that this figure shows a pixel which has been prepared in accordance with practice of the present invention to include a single fluid-assay sensor which possesses, or hosts, two (plural) potential fluid-material assay sites.
  • Fig. 13 to Fig. 18 provide block/ schematic diagrams illustrating the various methodological steps which characterize the preferred and best mode manner of practicing the present invention.
  • Fig. 19 to Fig. 26, inclusive provide block/ schematic diagrams illustrating the various methodological steps which characterize the preferred and best mode manner of practicing the present invention.
  • Fig. 27 to Fig. 31 , inclusive provide block-schematic diagrams that illustrate different ways of viewing the methodologic practice steps of the present invention.
  • Fig. 32 to Fig. 36, inclusive help to describe various aspects of the above-mentioned, illustrative DNA fluid assay, with respect to which a controlled heat field may be employed, and also time sampling may be used, to furnish different axes of assay-result output information obtainable from practice of the present invention.
  • Fig. 1 and Fig. 2 indicated generally at 20 is a fragmentary portion of a precursor, digitally-addressable, pixelated, fluid-assay, active-matrix micro-structure .
  • Micro-structure 20 takes the form herein of a column-and-row array 22 of plural, individually externally addressable pixels, such as those shown at 24 , 26, 28 , 30 , 32 , formed, as will shortly be described, on an appropriate supporting, conventional-material, preferably glass or plastic, substrate 34.
  • substrate 34 will be considered to be a glass substrate.
  • an internal crystalline-structure processing approach may be employed to create certain desired mechanical characteristics, such as the bending characteristics of a cantilever beam like that pictured in Fig. 1 , or the configurations of a collection of material spikes, like that collection which appears in Fig. 8 to Fig. 1 OC, inclusive .
  • Such internal crystalline-structure processing methodology is fully described in U . S . Patent No . 7, 125 ,45 1 B2 , and accordingly, the disclosure content of that patent is hereby incorporated herein by reference in order to provide background information respecting such processing methodology.
  • various non-critical dimensions may be chosen, for example, to define the overall lateral size of a precursor micro-structure, such as micro-structure 20.
  • the number of pixels organized into the relevant, overall row-and-column matrix may readily be chosen by one practicing the present invention.
  • a precursor micro-structure, such as micro-structure 20 might have lateral dimensions lying in a range of about 0.4 x 0.4-inches to about 2 x 2-inches, and might include an equal row-and-column array of pixels including a total pixel count lying in a range of about 100 to about 10 ,000. These size and pixel-count considerations are freely choosable by a practicer of the present invention.
  • a bracket 36 and a double-headed, broad arrow 38 represent an appropriate communication/ addressing connection, or path, between pixels in micro-structure 20 and a suitable digital computer, such as the computer shown in block form in Fig. 1 at 40.
  • a suitable digital computer such as the computer shown in block form in Fig. 1 at 40.
  • Such a path exists and is employed under circumstances where a precursor micro-structure, such as micro-structure 20 , is being (a) functionalized, or (b) "read” after the performance of a fluid-material assay.
  • This inclusion of computer 40 in Fig. 1 has been done to help illustrate and describe the completed precursor-micro-structure utility of the present invention.
  • each of the mentioned precursor pixels is essentially identical to each other pixel, although, as will later be explained herein, this is not a necessary requirement of the present invention.
  • This "not-necessary" statement regarding the characteristics of the present invention is based upon a clear understanding that there are various end-result fluid-assay applications with respect to which appropriately differentiated precursor pixels might be fabricated in a single, precursor micro-structure array.
  • pixel 24 In general terms, and using pixel 24 as an illustration to explain the basic construction of each of the precursor pixels shown in array 22 , included in pixel 24 are several, fully integrated, pixel-specific components, or substructures. These include, as part of more broadly inclusive pixel-specific electronic structure , ( 1 ) thin-film, digitally-addressable electronic switching structure, (2) a non-functionalized, precursor, individually remotely digitally-addressable and accessible assay sensor 24a which hosts a prospective, functionalizable assay site 24a 1 ? and (3) what is referred to herein as a pixel-bathing, ambient environmental, electromagnetic-field-creating structure 24b.
  • Field-creating structure 24b which is also remotely, or externally, individually digitally-addressable and accessible, is constructed to create, when energized, any one or more of three different kinds of assay-site-bathing, pixel-bathing, ambient, environmental electromagnetic fields in the vicinity of sensor 24a, including a light field, a heat field, and a non-uniform electrical field. While structure 24b, as was just mentioned, may be constructed to create one or more of these three different kinds of fields, in the micro-structure pictured in Fig. 1 and Fig. 2, field-creating structure 24b has been designed with three field-creating subcomponents 24b 1 ⁇ 24b2 and 24b3.
  • Subcomponent 24bi is capable of creating a pixel-bathing light field, subcomponent 24b2 a pixel-bathing heat field, and subcomponent 24b3 a pixel-bathing non-uniform electrical field. More will be said about these three different kinds of pixel-bathing, field-creating subcomponents shortly.
  • a bathing electromagnetic field of an appropriate selected character during pixel functionalization operates to create, within a pixel and adjacent an assay site, an ambient environmental condition wherein relevant chemical, biochemical, etc. reactions regarding functionalization flow material can take place , at least at the prepared, sensor-possessed assay site, or sites, to ensure proper functionalization at that site.
  • a "prepared assay site” might typically, i. e. , conventionally, be defined by a sensor borne area of plated gold.
  • each precursor pixel is appropriately prepared with one or more conventional electronic switching device(s) (part of the mentioned electronic switching structure) relevant to accessing and addressing its included sensor and assay site, and to energizing its field-creating structure . Illustrations of such devices are given later herein.
  • Fig. 2 indicated generally at 42 , 44 are two different communication line systems which are suitably created, and operatively connected to the field-creating structures in the illustrated pixels, and to the assay sensors and assay sites shown in these pixels.
  • the upper, fragmented ends of line systems 42 , 44 in Fig. 2 are embraced by a bracket marked with the two reference numerals 36, 38, which bracket represents the previously mentioned "path" of operative connection shown to exist in Fig. 1 between micro-structure 20 and computer 40.
  • Line system 42 is utilized by such a computer to energize pixel-bathing, field-creating subcomponents during a functionalization procedure, and also to energize these same field-creating subcomponents, where appropriate, during reading-out of the results of a performed assay.
  • Line system 44 on a pixel-by-pixel basis, directly couples to computer 40 output responses derived from ultimately functionalized assay sites.
  • Fig. 3 illustrates several different ways in which ultimately functionalized pixels (i. e . , non-precursor pixels) , such as fully functionalized versions of the pixels in array 22 , may, as enabled by the methodology of the invention, be organized and even differentiated in the hands of a user who is provided with a resulting, fully-rendered (i.e . , functionalized) matrix.
  • functionalized pixels i. e . , non-precursor pixels
  • dots which appear throughout in a row-and-column arrangement in Fig. 3, represent the locations of full-matrix, next-adjacent pixels constructed during practice of this invention.
  • One way of visualizing utilization of the full-matrix precursor structure, as represented by the full array of "dots" in Fig. 3, is to recognize that every pixel thus represented by one of the mentioned dots may be commonly functionalized to respond to a single, specific fluid-assay material.
  • marked regions A, B , C in Fig. 3 illustrate three other, representative, possible pixel functionalization patterns (specifically lower-pixel-count, submatrix patterns) that are accommodated by the utility of the present invention.
  • region A which is but a small, or partial, region, or patch, of the overall matrix array 22 of pixels
  • a functionalized submatrix pattern has been created, as illustrated by solid, horizontal and vertical intersecting lines, such as lines 48, 50, respectively, including rows and columns of next-adjacent pixels, which pixels are all commonly functionalized for a particular fluid-material assay.
  • lines 48, 50 intersecting lines
  • next-adjacent pixels which pixels are all commonly functionalized for a particular fluid-material assay.
  • different patches, or fragmentary areas, of next-adjacent pixels may be differently functionalized so that a single matrix array can be used differently with these kinds of patch submatrices to perform, for example, plural, different, fluid-material assays.
  • intersecting, solid, horizontal and vertical lines, such as lines 52 , 54 , respectively, and intersecting, dashed, horizontal and vertical lines, such as lines 56, 58 , respectively, illustrate two, different lower-pixel-count, submatrix functionalization patterns which fit each into the category mentioned earlier herein as a ⁇ bi-alternate" functionalization pattern which effectively creates two, large-area-distribution submatrices within the overall matrix array 22 of pixels.
  • These two pixel submatrices are distributed across the entire area of the overall matrix array, and are characterized by rows and columns of pixels which "sit" two pixel spacings away from one another.
  • Fig. 3 illustrates another lower-pixel-count, submatrix functionalization pattern wherein intersecting, light, solid, horizontal and vertical lines, such as lines 60, 62 , respectively, intersecting dashed, horizontal and vertical lines, such as lines 64 , 66, respectively, and intersecting, thickened, solid, horizontal and vertical lines, such as lines 68, 70, respectively, represent what was referred to herein earlier as a "tri-alternate" functionalization arrangement distributed over the entire matrix array 22 of pixels -- effectively dividing that array into three overlapping submatrices.
  • FIG. 4 and Fig. 5 these two figures illustrate, schematically and fragmentarily, two different kinds of pixel-bathing, light-field-creating subcomponents creatable in the practice of the invention.
  • FIG. 4 shown specifically in Fig. 4 is a fabricated, energizable, optical medium 72 which is energized/ switched directly by the operation of a control transistor (an electronic switching device) shown in block form at 74.
  • This control transistor has an operative connection to previously mentioned line system 42.
  • a sinuous arrow 76 extends from medium 72 toward prospective assay site 24ai which is hosted on sensor 24a. Arrow 76 schematically pictures the creation of a pixel-bathing, field of light in the vicinity of site 24ai .
  • an appropriately constructed optical beam device 78 having a light output port 78a, is switched on and off by means of an optical switching device 80 (an electronic switching device) which is fed light through an appropriately formed optical beam structure 82 which in turn is coupled to an off-pixel source of light.
  • Switching of optical switching device 80 is performed by a computer, such as previously mentioned computer 40, and via previously mentioned line system 42.
  • a sinuous arrow 84 represents a path of light flow to create a pixel-bathing field of light in the vicinity of prospective assay site 24ai .
  • optical media In each of the possible optical field-creating structures shown in Fig. 5 and Fig. 6, there are different specific arrangements of optical media, well-known to those skilled in the art, which may be built during practice of the invention and employed herein .
  • one such medium might have a horizontal-style configuration, and another arrangement might be characterized by a vertical- style arrangement.
  • Such arrangements are well-known and understood by those skilled in the relevant art.
  • Fig. 6 and Fig. 7 there are illustrated, schematically, two different, electronically switchable , pixel-bathing, heat-field-creating subcomponents, one of which, namely that one which is pictured in Fig. 6, may be used at the location designated 24b2 in Fig. 1 , and the other of which, namely that one which is shown in Fig. 7 , may be used at the location of an on-sensor-24a site 24d which is shown only in Fig. 7.
  • FIG. 7 As was mentioned earlier herein, entirely conventional and well-known, or recently introduced (see above-referred-to U. S. Patent No. 7, 125,451 B2 with regard to portions of the structure shown in Fig. 7) , specific processes may be employed, in the overall practice of this invention, to produce the switchable heat-field-creating subcomponents illustrated in these two figures.
  • the first-mentioned version of a heat-field-creating subcomponent is shown generally at 86 in Fig. 6.
  • This subcomponent (86) is also labeled 24b2 (in Fig. 6) in order to indicate its relationship to what has already been discussed above regarding the illustrations provided in Fig. 1 and Fig. 2.
  • the heat-field-creating subcomponent version illustrated generally at 88 in Fig. 7 is one which is shown as having been formed directly adjacent prospective assay site 24ai on a portion of assay sensor 24a, and specifically, formed directly on the beam 90a of a cantilever-type micro-deflection device 90 whose basic material body has been formed specifically utilizing the process mentioned above referred to as internal crystalline- structure processing.
  • an electrical signaling structure 92 which may take the form of any suitable electrical device that responds to bending in beam 90a to produce a related electrical output signal which may be coupled from the relevant pixel ultimately to an external computer, such as computer 40.
  • FIG. 8 illustrate various aspects of an electronically switchable, pixel-bathing, non-uniform-electrical- field-creating structure 94 which may be created within a pixel, such as within pixel 24 at the site shown at 24b3 in Fig. 1 and Fig. 2.
  • the mechanical spike structures seen in these figures have been fabricated employing the crystalline-structure-processing methodology described in the above-referred U. S. Patent No. 7, 125,451 B2.
  • the structure suggested herein for the creation of a non-uniform electrical field takes the form of a sub-array of very slender, approximately equal-height micro-spikes, such as those shown at 94a in Fig. 9 , with regard to which electrical energization, as by a computer, such as computer 40 , results in the production of an appropriate pixel-bathing, non-uniform electrical field, shown generally and very schematically in a cloud-like fashion at 96 in Fig. 9.
  • Figs . 1 OA, 1 OB and 1 OC illustrate several, different, representative micro-spike configurations and arrangements which might be used to characterize a non-uniform electrical field-creating subcomponent.
  • Such micro-spikes are simply illustrative of one of various kinds of different, electronically switchable structures which may be created within a field-creating structure in a pixel to develop, when energized, a suitable , non-uniform electrical field.
  • Fig. 1 OA illustrates modified micro-spike structures 94a regarding which distributed micro-spikes may have, either uniformly, or differentially, different heights lying within a user-selectable height range generally indicated at H .
  • Fig. 1 OB illustrates an arrangement wherein micro-spikes 94a are configured like those shown in Fig. 8 and Fig. 9, except for the fact that these Fig. 17B micro-spikes are more densely organized, as indicated by next-adjacent, interspike distance D .
  • Such an interspike distance is freely chooseable by a user, and need not be uniform throughout a full sub-array of micro-spikes.
  • What is illustrated in Fig. 1 OC is an arrangement wherein the pictured micro-spikes 94a may have several differentiating characteristics, such as differentiating heights and sharpnesses (i.e . , pointednesses) .
  • FIG. 1 1 is a modified fragmentary region drawn from the fragmentary illustration of Fig. 1.
  • This figure specifically illustrates a pixel 98, constructed as a part of practice of the present invention, and possessing two assay sensors 98a, 98b, each of which hosts but a single prospective assay site 98ai , 98b i , respectively.
  • the modification illustrated in Fig. 12 shows an arrangement wherein a pixel 100 , also constructed as a part of practice of the present invention, possesses a single sensor 100a which is structured so as to host two, different, potential assay sites 10Oa 1 and 100a2.
  • a precursor pixel-matrix structure which is formed utilizing the above-mentioned low-temperature TFT and Si technology, is provided preferably on a glass or plastic substrate, whereby, ultimately, and completely under the control of a recipient-user's selection, each pixel in that matrix is individually and independently functionalizable to display an affinity for at least one specific fluid-assay material, and following such functionalization, and the subsequent performance of a relevant assay, individually and independently digitally readable to assess assay results.
  • a precursor pixel-matrix structure which is formed utilizing the above-mentioned low-temperature TFT and Si technology, is provided preferably on a glass or plastic substrate, whereby, ultimately, and completely under the control of a recipient-user's selection, each pixel in that matrix is individually and independently functionalizable to display an affinity for at least one specific fluid-assay material, and following such functionalization, and the subsequent performance of a relevant assay, individually and independently digitally readable to assess assay results.
  • the invention thus takes the form of an extremely versatile and relatively low-cost matrix assay precursor structure, also referred to herein interchangeably as a microstructure . It is a precursor structure in the sense that, as has just been mentioned above , it is not yet an assay-material-specific-functionalized assay structure .
  • the structure of this invention is therefore one which is providable, as a singularity, to a user, in a special status which enables that user selectively to functionalize pixels in the structure, with great versatility, to perform one, or even plural different (as will be explained) , type(s) of fluid-material assay(s) .
  • active-matrix refers to a pixelated structure wherein each pixel is controlled by and in relation to some form of digitally-addressable electronic structure, which structure includes digitally-addressable electronic switching structure, defined by one or more electronic switching device(s) , operatively associated, as will be seen, with also-included pixel-specific assay-sensor structure and pixel-bathing electromagnetic field-creating structure -- all formed preferably by low-temperature TFT and Si technology as mentioned above .
  • bi-alternate refers to a possible matrix condition enabled by the present invention, wherein every other pixel in each row and column of pixels may selectively become commonly functionalized for one, specific type of a fluid-material assay. This condition effectively creates, across the entire area of the overall matrix of the invention, two differently functionalizable submatrices of pixels (what can be thought of as a two-assay, single-overall-matrix condition) .
  • tri-alternate refers to a similar condition, but one wherein every third pixel in each row and column may selectively become commonly functionalized for one, specific type of a fluid-material assay. This condition effectively creates, across the entire area of the overall matrix, three , differently functionalizable submatrices of pixels (what can be thought of as a three-assay, single-overall-matrix condition) .
  • submatrices are, of course, possible, and one other type of submatrix arrangement is specifically mentioned hereinbelow.
  • a submatrix functionalization approach regarding an overall matrix made in accordance with the present invention that approach may be employed to enable either (a) several, successive same-assay-material matrix-assay uses with the same overall matrix, or (b) several successive different-assay-material submatrix-assay uses also employing the same overall matrix.
  • assay-site functionalization is in all other respects essentially conventional in practice .
  • Such functionalization is, therefore , insofar as its conventional aspects are concerned, well known to those generally skilled in the relevant art, and not elaborated herein, but for a brief mention later herein noting the probable collaborative use, in many functionalization procedures, of conventional flow-cell assay-sensor-functional processes.
  • Each prepared "precursor" pixel which is an active-matrix pixel as that language is employed herein, includes, as was mentioned, at least one, digitally-addressable assay sensor which is designed to possess, or host, at least one ultimately to-be-functionalized fluid-assay site that will have and display an affinity for a selected, specific fluid-assay material.
  • Each such pixel also includes, as earlier indicated, an ⁇ on-board” , digitally-addressable, assay-site-bathing (also referred to as "pixel-bathing") , electromagnetic-field-creating structure (part of a thin-film electronic switching structure) which, among other things, is controllably energizable, as will be explained, (a) to assist in the functionalization of such an assay site for the performance of a specific kind of fluid-material assay, and (b) to assist (where appropriate) in the output reading of the result of a particular assay.
  • an ⁇ on-board digitally-addressable, assay-site-bathing (also referred to as “pixel-bathing")
  • electromagnetic-field-creating structure part of a thin-film electronic switching structure
  • This field-creating structure is capable, via the inclusion therein of suitable, different, field-creating subcomponents, and in accordance with the present invention, of producing, as an ambient, pixel-bathing field environment within its respective, associated pixel, any one or more of (a) a light field, (b) a heat field, and (c) a non-uniform electrical field.
  • the invention thus offers an extremely flexibly employable , staple-like, pixelated, precursor, fluid-assay, active-matrix structure, or micro-structure, wherein the individual pixels are not initially pre-ordained to function responsively with any specific fluid-assay material, but rather are poised with a readiness to have their respective , associated assay sensors later user-functionalized to respond with specificity to such an assay material.
  • each pixel includes a least one, and may include more than one, assay sensor(s) , with each such assay sensor being ultimately functionalizable to host, or possess, at least one, but optionally and selectively plural, assay-material-specific assay sites that are functionalized appropriately for such materials.
  • subj ect precursor structure of this invention it is entirely possible for a user of the subj ect precursor structure of this invention to create plural, different unified areas (i.e. , unified lower-pixel-count submatrices defined by next-adjacent, side-by-side pixels) within the overall, entire matrix structure which have their respective submatrix pixels functionalized to respond to a specific type of fluid-assay material, with each such different submatrix area being capable of responding to respective , different assay materials.
  • unified areas i.e. , unified lower-pixel-count submatrices defined by next-adjacent, side-by-side pixels
  • pixels in a group included in full matrix, or in a smaller-pixel-count submatrix may be functionalized for assay use utilizing plural different levels, or intensities, of functionalization-assist fields, such as intensity-differentiated heat and/ or non-uniform electrical fields.
  • Such differentiated field-intensity functionalization can yield, following an assay, information regarding how an assay's results are affected by such "field-differentiated" pixel functionalization.
  • assay results may be observed by reading pixel output responses successively under different (changed) ambient field conditions that are then presented as "bathing" fields seriatim to information-outputting pixels.
  • time-axis output data may easily be gathered on a pixel-by-pixel basis via pixel-specific, digital output sampling.
  • a unique, precursor (“blank-slate-style”) , pixelated active matrix, useable ultimately in a fluid-material assay, has been illustrated and described.
  • This matrix has a structure whereby, ultimately, and completely under the control of a matrix-recipient-user's selection, each pixel in that matrix is individually and independently functionalizable to display an affinity for at least one specific fluid-assay material, and following such functionalization, and the subsequent performance of a relevant assay, individually and independently digitally readable to assess assay results.
  • the matrix structure of the invention utilizes a low-cost substrate material, such as glass or plastic, and features the low-temperature fabrication on such a substrate of supported pixel structures, including certain kinds of special internal components or substructures, all formed preferably by low-temperature TFT and Si technology as discussed above .
  • the matrix of the invention has the characteristics of a "staple" in commerce -- a key factor which contributes to its special versatility with respect to how it can freely be functionalized in many ways by a user for employment in a fluid-material assay.
  • Independent digital addressability of each pixel introduces interesting opportunities (not offered by prior art structures) for preparing to conduct, and ultimately conducting, such assays in many new ways, including ways that include examining assay results on kinetic and time-based axes of information.
  • a single matrix may be employed in one-to-many fluid-material assays .
  • a novel fluid-material assay matrix structure also referred to herein as a microstructure, which takes the form of a pixelated, active-matrix, row-and-column, fluid-assay, micro-structure characterized by a selected grouping of individually electronically-digitally-addressable pixels, which pixel, and their contents, are formed preferably on a glass or plastic substrate utilizing the above-mentioned low-temperature TFT and Si technology.
  • the concepts of digital addressability and energizing expressed herein are intended to refer to computer-controlled addressability and energizing.
  • the pixels in this selected grouping which may include either an entire matrix of pixels, or one of a number of possible lower-pixel-count submatrices (later to be described herein) within an overall matrix, have been appropriately prepared on a supporting substrate, with each pixel therein possessing, in addition to appropriate, relevant, computer-accessible electronic switching structure, an included assay sensor which hosts an assay site that has been affinity-functionalized to assist in the performance of a particular kind of fluid-material-specific assay.
  • assay-site functionalization is in all other respects essentially conventional in practice .
  • Such functionalization is, therefore , insofar as its conventional aspects are concerned, well known to those generally skilled in the relevant art, and not elaborated herein, but for a brief mention later herein noting the probable collaborative use, in many functionalization procedures, of conventional flow-cell assay- sensor-functional processes.
  • Each pixel which is an active-matrix pixel as that language is employed herein, also includes, as was mentioned, a special, pixel-specific, digitally and controllably energizable and employable, assay-site-bathing (also referred to as "pixel-bathing”) electromagnetic field-creating structure which may be used, selectively and optionally, as a special assistant in the above-mentioned, "special-information-axis" reading-out of assay results, to generate a selected type of environmentally-pixel-bathing electromagnetic field, such as a light field, a heat field, and a non-uniform electrical field.
  • pixel-by-pixel assay-result output reading may also be accomplished in appropriate circumstances without any use of the field-creating structure.
  • This interesting and unique field-creating feature of the invention coupled with the invention's enablement of pixel-by-pixel, assay-result output reading, are what introduce and promote, among other things, the possibility of deriving assay-result data, including time-based and kinetic assay-reaction data, effectively along the above-suggested, special information axes not enabled by prior art devices.
  • pixels in an appropriately functionalized group of pixels may have been, before matrix delivery to a user, initially functionalized utilizing plural different intensities of functionalization-assist electromagnetic fields, such as intensity-differentiated heat and/ or non-uniform electrical fields.
  • Such differentiated field-intensity functionalization which becomes reflected in a final matrix, and which was performed by pixel-on-board electromagnetic field-creating structures, can, in an assay output-reading situation, yield information regarding how an assay's results are affected by "field-differentiated" prepared-pixel functionalization, also referred to herein as assay-site functionalization .
  • assay results may be observed by reading pixel output responses successively under different ambient field conditions that are then "presented" seriatim as spatial bathing fields to information-outputting pixels.
  • time-axis output data may easily be gathered on a pixel-by-pixel basis via pixel-specific, digital output sampling.
  • the invention thus takes the form of an extremely versatile and relatively low-cost fluid-material assay structure , which, because of its pixel-by-pixel functionalization characteristic, may be constructed, and delivered to an assay-performing user (as will be seen from discussion text presented hereinbelow) in a variety of different pre-assay conditions .
  • a finished, user-delivered matrix structure constructed in accordance with the present invention may be delivered with all of its pixels functionalized to handle a single, specific assay.
  • such a matrix structure may be delivered to a user with different pixels functionalized differently (i.e . , submatrix functionalization) so as to enable a single matrix to be employed in the conducting of plural, different assays.
  • each pixel in that matrix is originally individually and independently functionalizable to display an affinity for at least one specific fluid-assay material, and following such functionalization, and the subsequent performance of a relevant assay, individually and independently digitally readable to assess assay results.
  • Independent digital addressability of each pixel introduces interesting opportunities (not offered by prior art structures) for conducting fluid-material assays in many new ways, including ways that include examining assay results on kinetic and time-based axes of information.
  • a single matrix may be employed in one-to-many fluid-material assays.
  • the matrix structure of the invention preferably utilizes a low-cost substrate material, such as glass or plastic, and features the low-temperature fabrication on such a substrate of supported pixel structures, including certain kinds of special internal components or substructures, all formed preferably by low-temperature TFT and Si technology as discussed above.
  • Fig. 13 to Fig. 18, inclusive and respectively these six figures illustrate the several, key, high-level steps which characterize the preferred and best mode manners of practicing the present invention to produce the precursor micro-structure, and its various unique features, set forth and discussed above. What is shown in these figures, therefore, will be presented now in the context of those key, contributed, methodologic invention steps - recalling that the specifics of these steps' individual implementations may be , and preferably are, carried out in various conventional ways, such as the earlier mentioned, or suggested, micro-structure, photolithographic (and other) patterning and fabrication practices used widely in, for example , the making of all kinds of thin-film, micro-device (e.g. , transistor device) structures.
  • micro-device e.g. , transistor device
  • the invention can be seen to be describable as being a method for producing a precursor, active-matrix, fluid-assay micro-structure including the steps of establishing (or alternatively establishing by way of utilizing low-temperature TFT and Si technology) a matrix array of non-functionalized pixels, and preparing at least one of these pixels for individual, digitally-addressed (a) functionalization, and (b) reading out, ultimately, of completed assay results.
  • the preparing step includes providing each pixel in the established array with a digitally-addressable ( 1 ) non-functionalized assay sensor, and (2) independent, electromagnetic field-creating structure disposed adjacent that pixel.
  • the invention may be seen as utilizing low-temperature TFT and Si technology to implement the providing step on and in relation to a glass or plastic substrate.
  • Fig. 13 which includes blocks, or steps, 102 (PRODUCING) , 104 (ESTABLISHING) and 106 (PREPARING) provides another kind of overview, even somewhat more specific than what was just stated immediately above, of the methodology of the present invention.
  • blocks(steps) 104 , 106 are shown to be functionally included within block(step) 102 , and interconnected therein by a sequence-indicating arrow 108.
  • the invention can be expressed verbally as a method for PRODUCING (step 102) a remotely digitally-addressable, pixelated, precursor, active-matrix, fluid-assay micro-structure , including the steps of (a) ESTABLISHING (step 104) , on a supporting substrate, an array of plural, non-assay-functionalized pixels, and then (b) PREPARING (step 106) each established pixel with electronically digitally-addressable electronic structure designed to effect, for and with respect to that pixel, and under the selection and control of a user, at least one of (a) selective, independent, fluid-assay-material-specific functionalization, and (b) assay-result output reading, utilizing, at least in part, communicative, electronic interaction between that pixel and a digital computer.
  • Fig. 14 further pictures the step of electronic-switching-structure PREPARING, i.e. , block 106. More specifically, this electronic-switching-structure PREPARING step is shown to include the companion, but not necessarily sequential, blocks, or steps, 1 10 (PROVIDING) and 1 12 (FORMING) .
  • Fig. 14 effectively describes the invention as taking the form of what is expressed in and by Fig. 13 , wherein, further, the PREPARING step, block 106, includes (a) PROVIDING (step 1 10) each pixel with at least one electronically, digitally-addressable assay sensor operatively connected to also provided electronically digitally-addressable electronic switching structure, and constructed to host at least one electronically, digitally-addressable, ultimately functionalizable assay site, and (b) FORMING (step 1 12) within each pixel an electronically, digitally-addressable electromagnetic field-creating structure also operatively connected to the also provided electronic switching structure, and which is selectively energizable by the mentioned computer to participate in at least one of ( 1) pixel functionalization, and (2) assay-result output reading with regard to a functionalized pixel.
  • PROVIDING step 1 10
  • each pixel with at least one electronically, digitally-addressable assay sensor operatively connected to also provided electronically digitally-
  • Fig. 15 relates to Fig. 14 in somewhat, though not completely, the same manner that Fig. 14 relates to Fig. 13 , in the sense that Fig. 15 further characterizes the methodology of the invention expressed in Fig. 14 by describing something more about the included functional content of one of the blocks/ steps pictured in Fig. 14.
  • Fig. 15 further characterizes the invention by elaborating the functional content of the step of PROVIDING, i. e. , block 1 10 - indicating that the PROVIDING step includes, as will be more fully set forth below, the step of FABRICATING (block 1 14) , and additionally includes the further step of
  • PRODUCING (block 1 16) .
  • a connecting line 1 18 indicates the just-mentioned "further step" relationship between blocks 1 14, 1 16.
  • FIG. 15 illustrates that, with respect to the invention as pictured in Fig. 14, the
  • PROVIDING of each pixel with the mentioned at least one electronically digitally-addressable assay sensor includes FABRICATING that sensor within the pixel as a micro-deflection device.
  • Fig. 15 also illustrates that the step of PROVIDING further includes the step of PRODUCING, on the fabricated micro-deflection device, a remotely, electronically, digitally-addressable electrical signaling structure which is operable to generate an electrical signal related to deflection of the micro-deflection device .
  • Fig. 16, in pictured blocks/ steps 1 14, 120 illustrates that the step of FABRICATING (block 1 14) the mentioned micro-deflection device takes the form of CREATING (block 120) a cantilever structure.
  • Fig. 17 employs blocks/ steps 1 12 (FORMING) and 122 (CONSTRUCTING) , along with "produced-precursor-structure" blocks 124, 126, 128 (still to be described) , to elaborate, somewhat, the functional content of the step of FORMING within each pixel an electronically, digitally-addressable electromagnetic field-creating structure.
  • Fig. 17 describes the functional condition that the step of
  • FORMING a field-creating structure includes CONSTRUCTING, within each pixel, at least one of (a) a light-field-creating (L) subcomponent (block 124) , (b) a heat-field-creating (H) subcomponent (block 126) , and (c) a non-uniform-electrical-field-creating (E) subcomponent(block
  • Fig. 18 further characterizes the CONSTRUCTING (L) step (blocks 122 , 124) of the invention by pointing out that it can take two different forms of a step referred to as MAKING (block 130) .
  • the step of CONSTRUCTING (L) (blocks 122 , 124) of a light-field-creating subcomponent involves the MAKING either of a pixel on-board light (POB) source, block 132, or of a pixel-communicative, on-substrate, optical beam structure (OBS), block 134, adapted for optical coupling to an off-pixel light source.
  • POB pixel on-board light
  • OBS optical beam structure
  • a precursor pixel-matrix structure which is formed utilizing the above-mentioned low-temperature TFT and Si technology, is created and provided preferably on a glass or plastic substrate, whereby, ultimately, and completely under the control of a recipient-user's selection, each pixel in that created matrix is individually and independently functionalizable to display an affinity for at least one specific fluid-assay material, and following such functionalization, and the subsequent performance of a relevant assay, individually and independently digitally readable to assess assay results.
  • the invention thus takes the form of a method for creating an extremely versatile and relatively low-cost assay precursor structure .
  • the precursor structure, also referred to herein interchangeably as a micro-structure, resulting from this method is a precursor structure in the sense , as has just been mentioned above, that it is not yet an assay-material-specific-functionalized assay structure.
  • the structure created by the methodology of this invention is one which is providable, as a singularity, to a user, in a special status which enables that user selectively to functionalize assay sites in its pixels with great versatility, to perform one, or even plural different (as will be explained) , type(s) of fluid-material assay(s) .
  • the methodology which is contributed to the state of the relevant sensor assay art by the present invention is a very high-level methodology.
  • it consists of a unique, high-level organization of steps which are cooperatively linked to produce a unique fluid-assay precursor structure.
  • Detailed features of the several high-level steps involved in the practice of this invention are , or may be, drawn from well-known and conventional practices aimed at producing various micro-structure devices and features, such as semiconductor matrixes, or arrays .
  • the invention does not reside in, or include, any of these feature details. Rather, it resides in the overall arrangement of steps that are capable of leading to the fabrication of the desired, end-result assay precursor micro-structure mentioned above .
  • assay-site functionalization is in all other respects essentially conventional in practice.
  • Such functionalization is, therefore, insofar as its conventional aspects are concerned, well known to those generally skilled in the relevant art, and not elaborated herein, but for a brief mention later herein noting the probable collaborative use , in many functionalization procedures, of conventional flow-cell assay- sensor-functional processes.
  • the subject end-result product takes the form of a micro-structure pixelated array, or matrix, of active pixels which are designed to be individually, i.e . , pixel-specifically, addressed and accessed, for at least two important purposes, by a digital computer.
  • the first of these purposes is to enable user-selectable functionalization of assay sites in pixels to become responsive to particular fluid-assay materials.
  • the second involves implementing user-selectable access to assay-site-functionalized pixels to obtain output readings of responses generated by those pixels regarding the result(s) of a performed fluid-material assay.
  • the end-result structure generally created by the methodology of this invention acts importantly as a kind of blank slate useable by a user to characterize an entire matrix array, or even simply portions of such an array, for the performance of a specific, or plural specific (different or same) , user-chosen fluid-material assay(s) .
  • active-matrix refers to a pixelated structure wherein each pixel is controlled by and in relation to some form of digitally-addressable electronic structure, which structure includes digitally-addressable electronic switching structure, defined by one or more electronic switching device(s) , operatively associated, as will be seen, with also-included pixel-specific assay-sensor structure and pixel-bathing electromagnetic field-creating structure-- all formed preferably by low-temperature TFT and Si technology as mentioned above .
  • bi-alternate refers to a possible , user-selectable matrix condition enabled by practice of the present invention, wherein every other pixel in each row and column of pixels may selectively become commonly functionalized for one, specific type of fluid-material assay.
  • This condition effectively creates, across the entire area of an overall matrix made by practice of the invention, two differently and/ or separately functionalizable , lower-pixel-count submatrices of pixels (what can be thought of as a two-assay, single-overall-matrix condition) .
  • tri-alternate refers to a similar condition, but one wherein every third pixel in each row and column may selectively become commonly functionalized for one, specific type of a fluid-material assay. This condition effectively creates, across the entire area of an overall matrix, three, differently and/ or separately functionalizable, lower-pixel-count submatrices of pixels (what can be thought of as a three-assay, single-overall-matrix condition) .
  • submatrix functionalization approach regarding an overall matrix made in accordance with the present invention
  • that approach may be employed to enable either (a) several, successive same-assay-material matrix-assay uses with the same overall matrix, or (b) several successive different-assay-material submatrix-assay uses, also employing the same overall matrix.
  • the use of a submatrix functionalization approach with respect to the precursor matrix structure produced by practice of the present invention enables a user to elect to perform selected assays at different pixel-distribution "granularities".
  • Each prepared "precursor" pixel which is an active-matrix pixel as that language is employed herein, includes, as was mentioned, at least one, electronically, digitally-addressable assay sensor which is designed to possess, or host, at least one ultimately functionalized, electronically digitally-addressable fluid-assay site that will have and display an affinity for a selected, specific fluid-assay material.
  • Each such pixel also includes, as earlier indicated, an "on-board”, digitally-addressable, assay-site-bathing (also referred to as “pixel-bathing”) , preferably thin-film, electromagnetic-field-creating structure which, among other things, is controllably energizable, as will be explained, (a) to assist in the functionalization of such a site for the performance of a specific kind of fluid-material assay, and (b) to assist (where appropriate) in the output reading of the result of a particular assay.
  • an "on-board”, digitally-addressable, assay-site-bathing also referred to as “pixel-bathing”
  • thin-film, electromagnetic-field-creating structure which, among other things, is controllably energizable, as will be explained, (a) to assist in the functionalization of such a site for the performance of a specific kind of fluid-material assay, and (b) to assist (where appropriate) in the output reading of the
  • This pixel-bathing, field-creating structure is capable, via the inclusion therein (by • way of practice of the present invention) of suitable, different, field-creating subcomponents, and in accordance with aspects of the present invention, of producing, as a pixel-bathing, ambient field environment within its respective, associated pixel, any one or more of (a) an ambient light field, (b) an ambient heat field, and (c) an ambient non-uniform electrical field.
  • the invention thus offers a methodology for producing an extremely flexibly employable , blank-slate, staple-like, pixelated, precursor, fluid-assay, active-matrix structure, or micro-structure, wherein the individual pixels are not initially pre-ordained to function responsively with any specific fluid-assay material, but rather are poised with a readiness to have their respective, associated assay sensors later user-functionalized to respond with specificity to such an assay material.
  • each pixel includes a least one, and may include more than one, assay sensor(s) , with each such assay sensor being ultimately functionalizable to host, or possess, at least one, but selectively plural, assay-material-specific assay sites that are functionalized appropriately for such materials.
  • a precursor micro-structure user to create (i.e. , functionalize) plural, different, internally unified (all internally alike) subareas (i. e. , unified lower-pixel-count submatrices defined by next-adj acent, side-by-side pixels) within an overall, entire matrix, and to functionalize such pixels to respond to one specific type of fluid-assay material, with each such different, internally unified area being functionalized to respond to respective, different assay materials.
  • pixels in a group of pixels contained in a full matrix, or in a lower-pixel-count submatrix may be functionalized utilizing plural different levels, or intensities, of functionalization-assist fields, such as intensity-differentiated heat and / or non-uniform electrical fields.
  • Such differentiated field-intensity functionalization can yield assay-result output information regarding how an assay's results are affected by "field-differentiated" pixel functionalization.
  • assay results may be observed by reading pixel output responses successively under different, pixel-bathing ambient electromagnetic field conditions that are then presented seriatim to information-outputting pixels .
  • time-axis output data may easily be gathered on a pixel-by-pixel basis via pixel-specific, digital output sampling.
  • the precursor matrix structure made by practice of the methodology of the invention utilizes, preferably, a low-cost substrate material, such as glass or plastic, and features, also preferably, the low-temperature fabrication on such a substrate of supported pixel structures, including certain kinds of special internal components or substructures, all formed preferably by TFT and Si technology as discussed above .
  • a low-cost substrate material such as glass or plastic
  • TFT and Si technology preferably, silicon on glass or plastic technology.
  • the unique matrix which is created by practice of the methodology of the present invention has the characteristics of a "staple" in commerce -- a key factor which contributes to its special, end-result versatility with respect to how it can freely be functionalized in many ways by a user for employment in a fluid-material assay.
  • a single matrix may be user-employed in "one-to-many" fluid-material assays.
  • TIRD EMBODIMENT The following will explain another embodiment of the present invention in reference to Figs 1 to 12 , and Figs 19 to 26.
  • the same reference numerals are given, and explanations thereof are omitted here.
  • micro-device e.g. , transistor-device
  • the ESTABLISHING step may be expressed in the context of utilizing low-temperature TFT and Si technology in relation to forming devices preferably on a glass or plastic substrate.
  • a selected pixel includes individually and controllably BATHING (block 206)
  • Fig. 2 1 which includes blocks, or steps, 202 (PRODUCING) , 204 (ESTABLISHING) and 2 10
  • blocks 210, 2 12 , 2 14, 216 are shown to be functionally included within block 202 , and interconnected therein by sequence-indicating arrows 2 18 , 220, 222 , 224.
  • the invention can be expressed verbally as a method for PRODUCING (block 202) a remotely digitally-addressable, pixelated, active-matrix, fluid-assay micro- structure, including the steps of (a) ESTABLISHING (block 204) , on a supporting substrate, an array of plural pixels, (b) PREPARING (block 2 10) each established pixel with digitally-addressable electronic structure designed to effect, for and with respect to that pixel, and under the control of an appropriately operatively connected digital computer, at least one of ( 1) selective, independent, fluid-assay-material-specific functionalization, and (2) assay-result output reading, (c) operatively CONNECTING (block 2 12) such a computer to the electronic structure which is associated with at least one of the established and prepared pixels, (d) employing the operatively connected computer, digital
  • Fig. 22 further pictures the step of PREPARING (block 2 10) . More specifically, this PREPARING step (block 2 10) is shown to include the companion, but not necessarily sequential, 226 (PROVIDING) and 228 (FORMING) steps. In the language of words, Fig. 22 therefore effectively describes the invention as taking the form of what is expressed in and by Fig.
  • the PREPARING step includes (a) PROVIDING (block 226) each pixel with at least one electronically, digitally-addressable assay sensor operatively connected to also provided electronically digitally-addressable electronic switching structure, and constructed to host at least one electronically, digitally-addressable, ultimately functionalizable assay site , and (b) FORMING (block 228) within each pixel an electronically, digitally-addressable electromagnetic field-creating structure also operatively connected to the also provided electronic switching structure, and which is selectively energizable by the mentioned computer to participate in at least one of ( 1 ) pixel functionalization, and
  • Fig. 23 relates to Fig. 22 in somewhat, though not completely, the same manner that Fig. 22 relates to Fig. 2 1 , in the sense that Fig. 23 further characterizes the methodology of the invention expressed in Fig. 22 by describing something more about the included functional content of one of the blocks/ steps pictured in Fig. 22. In particular, Fig. 23 further characterizes the invention by elaborating the functional content of the step of PROVIDING,
  • the PROVIDING (block 226) step includes, as will be more fully set forth below, the step of FABRICATING (block 230) , and additionally includes the further step of PRODUCING (block 232) .
  • a connecting line 234 indicates the just-mentioned "further step" relationship between blocks 230 , 232.
  • Fig. 23 illustrates that, with respect to the invention as pictured in Fig. 22 , the PROVIDING (block 226) of each pixel with the mentioned at least one electronically digitally-addressable assay sensor includes
  • FABRICATING (block 230) that sensor within the pixel as a micro-deflection device.
  • Fig. 23 also illustrates that the step of PROVIDING (block 226) further includes the step of PRODUCING (block 232) , on the fabricated micro-deflection device, a remotely, electronically, digitally-addressable electrical signaling structure which is operable to generate an electrical signal related to deflection of the micro-deflection device .
  • Fig. 24 in pictured blocks/ steps 230 , 236 illustrates that the step of FABRICATING (block 230) the mentioned micro-deflection device takes the form of CREATING (block 236) a cantilever structure.
  • Fig. 25 employs blocks/ steps 228 (FORMING) and 238 (CONSTRUCTING) , along with "produced -structure" blocks 240, 242 , 244 (still to be described) , to elaborate, somewhat, the functional content of the step of FORMING (block 228) within each pixel an electronically, digitally-addressable electromagnetic field-creating structure .
  • Fig. 25 employs blocks/ steps 228 (FORMING) and 238 (CONSTRUCTING) , along with "produced -structure" blocks 240, 242 , 244 (still to be described) , to elaborate, somewhat, the functional content of the step of FORMING (block 228) within each pixel an electronically, digitally-addressable electromagnetic field-creating structure .
  • Fig. 25 employs/ steps 228 (FORMING) and 238 (CONSTRUCTING) , along with "produced -structure" blocks 240, 242 , 244 (still to be described) , to elaborate, somewhat, the functional content of the step of
  • a field-creating structure includes CONSTRUCTING (block 238) , within each pixel, at least one of (a) a light-field-creating (L) subcomponent (block 240) , (b) a heat-field-creating (H) subcomponent (block 242) , and (c) a non-uniform-electrical-field-creating (E) subcomponent(block 244) .
  • Fig. 26 further characterizes the CONSTRUCTING (L) step (blocks 238, 240) of the invention by pointing out that it can take two different forms of a step referred to as MAKING (block 246) .
  • the step of CONSTRUCTING (L) (blocks 238 , 240) of a light-field-creating subcomponent involves the MAKING (block 246) either of a pixel on-board light (POB) source (block 248) , or of a pixel-communicative, on-substrate, optical beam structure (OBS) (block 250) , adapted for optical coupling to an off-pixel light source.
  • POB pixel on-board light
  • OBS optical beam structure
  • pixel functionalization may be performed under circumstances wherein it is aided by the presence and use , in each pixel, of the included pixel-bathing electromagnetic field-creating structure which is, when so used, remotely and controllably energized under the management of an appropriate digital computer, to bathe the pixel-associated assay sensor and its possessed assay site(s) with such a field (light, heat and / or non-uniform electrical) .
  • electromagnetic field-creating structure which is, when so used, remotely and controllably energized under the management of an appropriate digital computer, to bathe the pixel-associated assay sensor and its possessed assay site(s) with such a field (light, heat and / or non-uniform electrical) .
  • this same field-creating structure has later utility, where appropriate, in relation to participating selectively in the reading-out of ultimately achieved, completed-assay results. More will be said about this invention-enabled later utility shortly.
  • Digitally addressed, pixel-by-pixel functionalization allows for the production of highly specialized and individualized fluid-material assays.
  • Such functionalization performed in the context of also employing, as an aid, the mentioned electromagnetic field-creating structure, enables a very high, selective versatility to be associated with finally functionalized pixels.
  • this same, per-pixel, digitally-addressable electromagnetic field-creating structure opens the door to permitting a number of highly specialized assay-result output reading practices.
  • the present invention utilizing the above-mentioned low-temperature TFT and "Si on glass or plastic substrate” technology, thus takes the form of a method for creating an extremely versatile and relatively low-cost digitally-addressable assay structure, also referred to herein interchangeably as a micro-structure .
  • the structure created by the methodology of this invention is one which is providable, as a singularity, to a user, in a status which enables that user to perform one, or even plural different (as will be explained) , type(s) of fluid-material assay(s) . It is also a structure which enables the useful reading out of completed assay results completely on a precision, pixel-by-pixel basis.
  • the methodology which is contributed to the state of the relevant sensor assay art by the present invention is a very high-level methodology.
  • it consists of a unique, high-level organization of steps which are cooperatively linked to produce a unique fluid-assay structure.
  • Detailed features of the several high-level steps involved in the practice of this invention are, or may be, drawn from well-known and conventional practices aimed at producing various micro-structure devices and features, such as semiconductor matrices, or arrays.
  • the invention does not reside in, or include , any of these feature details. Rather, it resides in the overall arrangement of steps that are capable of leading to the fabrication of the desired, end-result assay micro-structure mentioned above.
  • assay-site functionalization is in all other respects essentially conventional in practice .
  • Such functionalization is, therefore , insofar as its conventional aspects are concerned, well known to those generally skilled in the relevant art, and not elaborated herein, but for a brief mention later herein noting the probable collaborative use, in many functionalization procedures, of conventional flow-cell assay- sensor-functional processes.
  • the subject end-result product takes the form of a micro-structure pixelated array, or matrix, of active pixels which are designed to be individually, i.e. , pixel-specifically, addressed and accessed, for at least two important purposes, by a digital computer.
  • the first of these purposes is to enable selective functionalization of assay sites in pixels to become responsive to particular fluid-assay materials.
  • the second involves enabling user-selectable access to functionalized pixels to obtain output readings of responses generated by those pixels regarding the result(s) of a performed fluid-material assay.
  • the structure generally created by the methodology of this invention allows for selective characterization of an entire matrix array, or even simply portions of such an array, for the performance of a specific, or plural specific (different or same) , user-chosen fluid-material assay(s) .
  • active-matrix refers to a pixelated structure wherein each pixel is controlled by and in relation to some form of digitally-addressable electronic structure, which structure includes digitally-addressable electronic switching structure, defined by one or more electronic switching device(s) , operatively associated, as will be seen, with also-included pixel-specific assay-sensor structure and pixel-bathing electromagnetic field-creating structure-- all formed preferably by low-temperature TFT and Si technology as mentioned above.
  • bi-alternate refers to a possible , selectable matrix condition enabled by practice of the present invention, wherein every other pixel in each row and column of pixels is selectively commonly functionalized for one, specific type of fluid-material assay.
  • This condition effectively creates, across the entire area of an overall matrix made by practice of the invention, two differently and/ or separately functionalized, lower-pixel-count submatrices of pixels (what can be thought of as a two-assay, single-overall-matrix condition) .
  • tri-alternate refers to a similar condition, but one wherein every third pixel in each row and column is selectively commonly functionalized for one, specific type of a fluid-material assay. This condition effectively creates, across the entire area of an overall matrix, three, differently and/ or separately functionalized, lower-pixel-count submatrices of pixels (what can be thought of as a three-assay, single-overall-matrix condition) .
  • Each prepared "precursor" pixel which is an active-matrix pixel as that language is employed herein, includes, as was mentioned, at least one, electronically, digitally-addressable assay sensor which is designed to possess, or host, at least one functionalized, electronically digitally-addressable fluid-assay site that will have and display an affinity for a selected, specific fluid-assay material.
  • Each such pixel also includes, as earlier indicated, an "on-board” , digitally-addressable, assay-site-bathing (also referred to as “pixel-bathing”) , preferably thin-film, electromagnetic-field-creating structure which, among other things, is controllably energizable, as will be explained, (a) to assist in the functionalization of such a site for the performance of a specific kind of fluid-material assay, and (b) to assist (where appropriate) in the later output reading of the result of a particular assay.
  • This pixel-bathing, electronic, field-creating structure is capable, via the inclusion therein (by way of practice of the present invention) of suitable, different, field-creating subcomponents, and in accordance with aspects of the present invention, of producing, as a pixel-bathing, ambient field environment within its respective , associated pixel, any one or more of (a) an ambient light field, (b) an ambient heat field, and (c) an ambient non-uniform electrical field.
  • each pixel includes a least one , and may include more than one, assay sensor(s) , with each such assay sensor being ultimately functionalized to host, or possess, at least one, but selectively plural, assay-material-specific assay sites that are functionalized appropriately for such materials.
  • submatrices it is possible to create (i.e. , to functionalize) plural, different, internally unified (all internally alike) subareas (i. e . , unified lower-pixel-count submatrices defined by next-adj acent, side-by-side pixels) within an overall, entire matrix, and to functionalize such pixels to respond to one specific type of fluid-assay material, with each such different, internally unified area being functionalized to respond to respective, different assay materials.
  • plural, different, internally unified (all internally alike) subareas i. e . , unified lower-pixel-count submatrices defined by next-adj acent, side-by-side pixels
  • pixels in a group of pixels contained in a full matrix, or in a lower-pixel-count submatrix may be functionalized utilizing plural different levels, or intensities, of functionalization-assist fields, such as intensity-differentiated heat and/ or non-uniform electrical fields.
  • Such differentiated field-intensity functionalization can yield assay-result output information regarding how an assay's results are affected by "field-differentiated" pixel functionalization.
  • assay results may be observed by reading pixel output responses successively under different, pixel-bathing ambient electromagnetic field conditions that are then presented seriatim to information-outputting pixels.
  • time-axis output data may easily be gathered on a pixel-by-pixel basis via pixel-specific, digital output sampling.
  • Pixel- specific, digitally-addressable, electromagnetic field-creating structures enable widely-varied, controlled pixel functionalization under different kinds of ambient field conditions, and also enable, ultimately, a rich range (time-sampling-based, and on additional, uniquely permitted information axes, such as field-intensity varying axes) of assay-result output reading possibilities, some of which have been specifically mentioned above .
  • the matrix structure made by practice of the methodology of the invention utilizes, preferably, a low-cost substrate material, such as glass or plastic, and features, also preferably, the low-temperature fabrication on such a substrate of supported pixel structures, including certain kinds of special internal components or substructures , all formed preferably by TFT and Si technology as discussed above.
  • FIG. 27 Fig. 27 to Fig. 3 1 , inclusive, and recognizing that assay performance in accordance with practice of the present invention is based upon use of a suitably provided, i. e. , made-available, device like micro-structure 20 shown in Fig. 1 and Fig. 2 , these five drawing figures illustrate the basic high-level methodology of the invention which is practiceable in conjunction with such a device .
  • a device like micro-structure 20 with appropriately functionalized pixels, sensors and assay sites is provided for use, and is placed in an assay-fluid environment, such as within a conventional flow-cell.
  • a computer like computer 40, is appropriately linked to the sensors, assay sites and field-creating structures in the device's pixels via communication/ addressing path structure 36, 38 shown in Fig. 1 and Fig. 2, and the device's pixels are then appropriately exposed to assay-fluid in the assay environment.
  • the pixels are digitally addressed/ accessed to request from their respective sensors and assay sites assay-reaction output results/ information so as to obtain, collect and store if desired, and report on, that information.
  • This pixel-by-pixel digital addressing may also be accompanied very effectively by simultaneous accessing and energizing of pixel-specific field-creating subcomponents to produce one or more kind(s) of field(s) , such as light, heat and electrical potential (or electrical gradient) fields, in the vicinities of addressed sensor assay sites in order to enhance assay-result information output.
  • field(s) such as light, heat and electrical potential (or electrical gradient) fields
  • output readings may be acquired at different, computer-controlled, static, or varying, electromagnetic field conditions, such as varying field-intensity conditions, and this may also be done in a sampling fashion on a time base, thus to open opportunities for gaining multiple "axes" of assay-result output information.
  • Fig. 27 which includes three blocks 300 , 302 , 304 , illustrates one specific way of visualizing the practice of the invention.
  • the invention can be expressed as being a method of performing a fluid-material assay utilizing a device including at least one active pixel having a sensor with an assay site functionalized for selected fluid-assay material, including the steps, following providing of the mentioned device, of (a) exposing the pixel's sensor assay site to such material (block 300) , and in conjunction with such exposing, and (b) employing the active nature of the pixel
  • Fig. 29 shows, in four blocks 308, 3 10 , 3 12 , 3 14 , several other ways of visualizing the practice of the assay performance methodology of the present invention.
  • the invention can be expressed as being a method for performing a fluid-material assay utilizing a pixelated assay matrix wherein each pixel possesses an assay sensor with a functionalized assay site, and is individually and remotely digitally addressable via the presence in the pixel of an active, selectively energizable electronic switching structure which is operatively connected to the sensor and its assay site.
  • the method steps from this viewpoint include , following providing of mentioned matrix device, (a) subjecting the matrix to an environment containing assay fluid in order to effect pixel-sensor assay-site reactions (block 308) , in connection with this subjecting step, (b) remotely, digitally and individually addressing selected pixel's included electronic switching structure (block 3 10) , and (c) , by that addressing step, requesting from the sensors' assay sites in the addressed pixels pixel-specific assay-result output information (block 312) .
  • this additional block (3 14) illustrates the additional step, which is a consequence of the requesting step, of obtaining from each of the selected pixels' sensors' assay sitess a result-output reading of any reaction associated with that pixel's included assay-sensor assay site .
  • Fig. 30 in the drawings illustrates, at least partially by blocks 3 10, 316, 3 18, a further description of the invention methodology which is based upon use of an assay support device wherein each pixel further includes individually remotely and digitally accessible and energizable electromagnetic field-creating structure that is both associated with the pixel's assay sensor, and also operatively connected to the pixel's included electronic switching structure.
  • This figure describes the methodology, as expressed above in relation to Fig. 29 in an augmented fashion by stating that the addressing step (block 3 10) further includes remotely, digitally and individually accessing and energizing a selected pixel's field-creating structure
  • Fig. 31 illustrates with a block 320 that, from an additional perspective the just-described "creating" step includes the step of providing at least one of (a) a singular, stable, and (b) a staged, time-variant, electromagnetic field environment of the type generally mentioned in relation to the description of Fig. 30. It is also the case that this producing (block 320) step includes the selectable practice of providing different pixel-specific electromagnetic field environments with respect to different pixels.
  • the illustration now to be described relates to the performance of a DNA fluid-material assay utilizing a matrix constructed in accordance with the above-described features of micro- structure 20 , and with the pixels in this micro-structure more specifically constructed in accordance with a sensor structure of the cantilever style which is illustrated in Fig. 35 in the drawings.
  • a DNA assay is performed utilizing a provided, pixelated matrix including appropriately functionalized sensors possessing predetermined (and not necessarily all the same) oligonucleotide probes.
  • This matrix is placed in a suitable fluid-assay environment, such as within a conventional flow-cell, and fluid-assay material is introduced into that environment.
  • a computer which is suitably connected operatively to the matrix's active pixels is employed, as desired, to request assay-result output information on a pixel-by-pixel basis, and also to access and energize the associated, pixel-specific heat-field-creating structures on a time-stable or time-varying basis to add interesting and highly informative output information.
  • a major issue relating to conventional DNA-assay arrays is so-called background signal associated with non-specific binding of labeled targets.
  • Such binding can be caused by cross-hybridization of targets with similar heterologous probes, and by random non-specific attachment of targets to probes distributed over a matrix array surface.
  • Cross-hybridization to heterologous probes depends on hybridization temperature, and can be decreased by precise temperature adjustment in the vicinity of probes.
  • non-specific binding differs from ' specific target-probe hybridization in terms of temperature dependence, and these two processes can be clearly distinguished by utilizing the "additional information axis" capability of the present invention, thereby obtaining a temperature-to-binding dependence category of output information.
  • a detected binding signal that does not match a profile for the specific, intended interaction can be considered to be a false positive signal.
  • the ability, thus, to perform hybridization of a target DNA or RNA molecule with multiple identical probes at different temperatures allows one to characterize the temperature dependence of target hybridization.
  • This dependence can be used as a fingerprint approach for specific target-probe interactions, and it can be used to discriminate false positive signals on a matrix array.
  • SNP Single Nucleotide Polymorphism
  • DNA assay applications in basic research and clinical diagnostics The ability to distinguish the so-called wild-type DNA target molecule from one that has a single sequence mismatch is based on different target-to-probe binding behaviors at different temperatures. For example,
  • Fig. 32 shows the typical expected temperature dependence of target-to-probe binding for a wild-type DNA (Owt) , and for three, corresponding mismatches OAt, OAc, and OAg.
  • Fig. 33 which illustrates this, shows representative temperature-to-binding-dependence curves, or plots, that would be obtained typically by using an array of numerous oligonucleotide assay probes for such a set of targets where different probes in this array are designed for, and are hybridized at, different temperatures.
  • Temperature variation in this setting will typically be performed independently for groups of assay sites (probes) that have been commonly functionalized to possess replicates of the same probe.
  • Fig. 33 indicates that the measurement (and plotting) of temperature-to-binding dependence will permit discrimination between the wild type and mismatching sequences as well as among different mismatches.
  • Assay-site-specific sets of heating elements will contribute to a way to perform hybridizations at different temperatures for individual probes within one pixelated matrix array, and will result in accommodating the obtaining of temperature-to-binding profiles, like those pictured in Fig. 33 , in a single test assay.
  • Fig. 34A shows a typical, expected hybridization signal for two different target and probe pairs at a constant temperature.
  • Saturation of the signal corresponds to the stage where hybridization equilibrium is achieved. If the two, pictured target-probe pairs I and II have a closely similar sequence (for example, in the case of an SNP assay) , the plots obtained for pairs I and II are difficult to distinguish. If, however, hybridization is performed at time-varying temperatures (Fig. 34B) , the resultant signal-to-time dependence plots have more complicated and perceivably different patterns. Such temperature variations
  • target-to-probe hybridization will cause an increase in a detected binding signal.
  • hybridization temperature exceeds the melting point for the subject target-probe pair, hybrids start to denature, causing a corresponding decrease in signal (see generally the right-side portion of Fig. 33) .
  • real-time detection of hybridization signals at time-varying temperatures can provide unique and readily distinguishable individual characteristics for each target-probe pair.
  • the upper "turn points" of plots I and II in Fig. 34B can be used to distinguish highly similar target sequences .
  • Temperature time varying can also be performed independently for several sensing elements (assay sites) that contain (have been functionalized to contain) replicates of the same probe.
  • DNA assay they also illustrate that characteristic of the present invention which enables the obtaining of assay-result output information on a time-based axis, as by sampling on such an axis.
  • a relevant cantilever "transducer signal" is associated with detection of a cantilever deflection that is caused by a surface-tension change due to bio-interactions occurring on the cantilever surface at the location of a functionalized assay site.
  • the ability, offered during practice of the present invention, to vary, over time, the temperature in the cantilever vicinity allows for generation of a changing cantilever deflection.
  • a "temperature oscillation” results in a related, basic oscillation of cantilever response (see the darker, upper solid line in Fig.
  • the present invention may be described as a method of performing a fluid-material assay employing an appropriately provided (i.e . , made available) computer-accessible device (note the discussion above) -- preferably a pixelated matrix device, including at least one active digitally-addressable pixel having a sensor with a digitally-addressable assay site functionalized for selected fluid-assay material, with the key steps of this method including, following, of course, providing such a device, exposing the pixel's sensor assay site to such material, and in conjunction with such exposing, and employing the computer-accessible, active nature of the provided device's pixel, remotely and digitally requesting from the pixel's sensor assay site an assay-result output report.
  • an appropriately provided (i.e . , made available) computer-accessible device note the discussion above) -- preferably a pixelated matrix device, including at least one active digitally-addressable pixel having a sensor with a digitally-addressable
  • the basic methodology further includes, in relation to the mentioned employing step, creating, relative to the sensor's assay site in the at least one pixel, a predetermined, pixel-specific electromagnetic field environment.
  • the creation of such an environment is enabled by the type of matrix structure of this invention, and is specifically enabled by the presence in the described matrix pixels of one or several digitally accessible and energizable electromagnetic field-creating structure(s) .
  • the embodiments and concrete examples of implementation discussed in the foregoing detailed explanation serve solely to illustrate the technical details of the present invention, which should not be narrowly interpreted within the limits of such embodiments and concrete examples, but rather may be applied in many variations within the spirit of the present invention, provided such variations do not exceed the scope of the patent claims set forth below.

Abstract

Selon l'invention, une micro-structure à matrice active, de dosage de liquide, précurseur, pixélisée, adressable numériquement, pixel par pixel comprend plusieurs pixels formés de préférence sur un substrat en verre ou en plastique. Chaque pixel formé au moyen d'une technique TFT et Si à basse température comprend (a) au moins un détecteur de dosage adressable numériquement, non fonctionnalisé et (b) une structure de création de champ électromagnétique énergisable et adressable numériquement disposée fonctionnellement à proximité de ce détecteur, cette structure étant énergisable sélectivement de manière à créer dans le voisinage d'au moins un détecteur de dosage, un environnement de champ électromagnétique ambiant structuré pour faciliter la fonctionnalisation, en tant qu'élément appartenant audit détecteur, d'au moins un site de dosage adressable numériquement qui affichera une affinité pour un matériau de dosage de liquide sélectionné.
PCT/JP2007/070021 2006-10-06 2007-10-05 Structure micro-pixélisée de dosage de liquide, structure précurseur micro-pixélisée de dosage de liquide, et procédés liés à la fabrication et à la réalisation WO2008044779A1 (fr)

Applications Claiming Priority (12)

Application Number Priority Date Filing Date Title
US84987506P 2006-10-06 2006-10-06
US60/849,875 2006-10-06
US11/827,335 2007-07-10
US11/827,176 US8232108B2 (en) 2006-10-06 2007-07-10 Method of making micro-pixelated fluid-assay structure
US11/827,176 2007-07-10
US11/827,335 US8236245B2 (en) 2006-10-06 2007-07-10 Micro-pixelated fluid-assay precursor structure
US11/827,175 US8236571B2 (en) 2006-10-06 2007-07-10 Method of making micro-pixelated fluid-assay precursor structure
US11/827,174 2007-07-10
US11/827,174 US8231831B2 (en) 2006-10-06 2007-07-10 Micro-pixelated fluid-assay structure
US11/827,175 2007-07-10
US11/888,491 2007-07-31
US11/888,491 US8232109B2 (en) 2006-10-06 2007-07-31 Micro-pixelated active-matrix fluid-assay performance

Publications (1)

Publication Number Publication Date
WO2008044779A1 true WO2008044779A1 (fr) 2008-04-17

Family

ID=39282964

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2007/070021 WO2008044779A1 (fr) 2006-10-06 2007-10-05 Structure micro-pixélisée de dosage de liquide, structure précurseur micro-pixélisée de dosage de liquide, et procédés liés à la fabrication et à la réalisation

Country Status (1)

Country Link
WO (1) WO2008044779A1 (fr)

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH11127900A (ja) * 1997-07-11 1999-05-18 Commiss Energ Atom 部分的加熱手段を備えた電極からなるチップベースの分析装置
JPH11344437A (ja) * 1998-05-29 1999-12-14 Canon Inc 面発光レーザーを用いた表面プラズモン共鳴センサ装置
JP2001235469A (ja) * 1999-12-15 2001-08-31 Hitachi Ltd 生化学反応検出チップ用基板およびその製造方法、生化学反応検出チップ、生化学反応を行うための装置および方法、ならびに記録媒体
JP2003004697A (ja) * 2000-12-22 2003-01-08 Seiko Epson Corp センサ・セル
JP2004001208A (ja) * 2002-04-23 2004-01-08 Sharp Corp 結晶化処理された、モノリシック一体化型機械デバイス、機械デバイスと電子デバイスとの組み合わせ、ならびにその製造方法およびシステム
JP2005077287A (ja) * 2003-09-01 2005-03-24 Seiko Epson Corp バイオセンサ及びバイオセンサの製造方法
WO2005029042A2 (fr) * 2003-09-23 2005-03-31 Massachusetts Institute Of Technology Fabrication et emballage de detecteurs de microcanaux suspendus
WO2005029059A1 (fr) * 2003-09-19 2005-03-31 Cambridge University Technical Services Limited Detection d'interactions moleculaires au moyen d'un transistor a effet de champ
JP2006170642A (ja) * 2004-12-13 2006-06-29 Hitachi Cable Ltd バイオセンサアレイ及びその製造方法
JP2006258469A (ja) * 2005-03-15 2006-09-28 Sharp Corp 核酸プローブ形成用基板

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH11127900A (ja) * 1997-07-11 1999-05-18 Commiss Energ Atom 部分的加熱手段を備えた電極からなるチップベースの分析装置
JPH11344437A (ja) * 1998-05-29 1999-12-14 Canon Inc 面発光レーザーを用いた表面プラズモン共鳴センサ装置
JP2001235469A (ja) * 1999-12-15 2001-08-31 Hitachi Ltd 生化学反応検出チップ用基板およびその製造方法、生化学反応検出チップ、生化学反応を行うための装置および方法、ならびに記録媒体
JP2003004697A (ja) * 2000-12-22 2003-01-08 Seiko Epson Corp センサ・セル
JP2004001208A (ja) * 2002-04-23 2004-01-08 Sharp Corp 結晶化処理された、モノリシック一体化型機械デバイス、機械デバイスと電子デバイスとの組み合わせ、ならびにその製造方法およびシステム
JP2005077287A (ja) * 2003-09-01 2005-03-24 Seiko Epson Corp バイオセンサ及びバイオセンサの製造方法
WO2005029059A1 (fr) * 2003-09-19 2005-03-31 Cambridge University Technical Services Limited Detection d'interactions moleculaires au moyen d'un transistor a effet de champ
WO2005029042A2 (fr) * 2003-09-23 2005-03-31 Massachusetts Institute Of Technology Fabrication et emballage de detecteurs de microcanaux suspendus
JP2006170642A (ja) * 2004-12-13 2006-06-29 Hitachi Cable Ltd バイオセンサアレイ及びその製造方法
JP2006258469A (ja) * 2005-03-15 2006-09-28 Sharp Corp 核酸プローブ形成用基板

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
BISWAL S.L. ET AL.: "Nanomechanical Detection of DNA Melting on Microcantilever Surfaces", ANAL. CHEM., vol. 78, 20 September 2006 (2006-09-20), pages 7104 - 7109, XP003022198 *
ESTRELA P. ET AL.: "Field effect of detection of biomolecular interactions", ELECTROCHIMICA ACTA, vol. 50, 1 July 2005 (2005-07-01), pages 4995 - 5000, XP005051383 *
LANG H.P. ET AL.: "Cantileverl array sensors", MATERIALSTODAY, vol. 8, no. 4, April 2005 (2005-04-01), pages 30 - 36, XP004797366 *
MIN YUE ET AL.: "A 2-D Microcantilever Array for Multiplexed Biomolecular Analysis", JOURNAL OF MICROELECTROCHEMICAL SYSTEMS, IEEE, vol. 13, no. 2, April 2004 (2004-04-01), pages 290 - 299, XP001200248 *

Similar Documents

Publication Publication Date Title
US8231831B2 (en) Micro-pixelated fluid-assay structure
US20120245049A1 (en) System and Method for Pixelated Fluid Assay
US8247196B2 (en) Real-time PCR of targets on a micro-array
JP5026978B2 (ja) マイクロアレイ上での複数標的のリアルタイム定量化
DE112006000374B4 (de) Verfahren zum Bilden eines biologischen Sensors
JP2009540290A (ja) Ｄｎａ検出用ミクロ電子工学センサ装置
JP2003107083A (ja) 棒状担体およびこれを具備するシリンダー反応容器
WO2012116385A1 (fr) Réseau de biocapteurs formé par des jonctions d'électrodes fonctionnalisées
Lai et al. Detection of DNA targets hybridized to solid surfaces using optical images of liquid crystals
DE102004056735A1 (de) Vorrichtung für die Durchführung und Analyse von Mikroarray-Experimenten
US20080079663A1 (en) Micro-pixelated fluid-assay precursor structure
CA2417889A1 (fr) Appareil servant a produire un gradient de temperature et procedes d'utilisation du gradient pour caracteriser des interactions moleculaires
CN100350249C (zh) 相互作用检测方法、生物测定装置以及用于生物测定的基板
TWI221523B (en) Bioassay method, bioassay device, and bioassay substrate
WO2008044779A1 (fr) Structure micro-pixélisée de dosage de liquide, structure précurseur micro-pixélisée de dosage de liquide, et procédés liés à la fabrication et à la réalisation
JP4200801B2 (ja) バイオアッセイ用基板
Treasurer et al. How Surfaces Affect Hybridization Kinetics
US8232108B2 (en) Method of making micro-pixelated fluid-assay structure
JP2004512514A (ja) 再スポット機能を有する高精度知能型バイオチップアレイヤー
US8236245B2 (en) Micro-pixelated fluid-assay precursor structure
US8236571B2 (en) Method of making micro-pixelated fluid-assay precursor structure
KR100298415B1 (ko) 패턴 형성장치 및 그를 이용한 패턴 형성방법
JP4218257B2 (ja) バイオアッセイ方法及びバイオアッセイ装置
US8236244B2 (en) Micro-pixelated fluid-assay structure with on-board addressable, pixel-specific functionalization
KR101162365B1 (ko) 바이오 어세이 방법, 바이오 어세이 장치 및 바이오어세이 기판

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 07829756

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 07829756

Country of ref document: EP

Kind code of ref document: A1