US4141687A — Automatic apparatus and method for the assay of f…

Claim 1

Independent Claim 133 words

Analysis apparatus, which comprises: means for flowing reaction mixtures, in turn, along a conduit and on a discrete basis, each of said reaction mixutures comprising a liquid phase including a fluid sample containing a constituent of interest and a solid phase comprising a first reagent bound to magnetically attractable particulate material, reaction taking place in the said mixture to form a reaction product, at least, on said particulate material; means along a portion of said conduit for magnetically trapping said particulate material in each of said reaction mixtures, so as to hold said solid phase against flow and separate said solid phase from the flowing liquid phase; and, downstream of said trapping means, means for determining said constituent of interest by selective analysis of said separated solid phase and/or said separated liquid phase.

Claim 2

Dependent Claim 133 words

Analysis apparatus, which comprises: means for flowing reaction mixtures, in turn, along a conduit and on a discrete basis, each of said reaction mixutures comprising a liquid phase including a fluid sample containing a constituent of interest and a solid phase comprising a first reagent bound to magnetically attractable particulate material, reaction taking place in the said mixture to form a reaction product, at least, on said particulate material; means along a portion of said conduit for magnetically trapping said particulate material in each of said reaction mixtures, so as to hold said solid phase against flow and separate said solid phase from the flowing liquid phase; and, downstream of said trapping means, means for determining said constituent of interest by selective analysis of said separated solid phase and/or said separated liquid phase.

Claim 3

Dependent Claim 24 words

Apparatus according to claim 1, which further includes: means for introducing said particulate material into admixture with each fluid sample flowing along said conduit.

Claim 4

Dependent Claim 34 words

Apparatus according to claim 1, wherein said trapping means comprises first magnetic means to provide a magnetic field in said portion of said conduit and substantially transverse of the direction of reaction mixture flow.

Claim 5

Dependent Claim 39 words

Apparatus according to claim 1, wherein said trapping means comprises first and second magnetic means to provide spaced magnetic fields in said portion of said conduit, said second magnetic means being downstream with respect to said first magnetic means.

Claim 6

Dependent Claim 18 words

Apparatus according to claim 4, which further includes: means for independently actuating said first and second magnetic means.

Claim 7

Dependent Claim 26 words

Apparatus according to claim 1, which further includes: means for passing wash liquid, at least, along said portion of said conduit intermediate said successive reaction mixtures.

Claim 8

Dependent Claim 63 words

Apparatus according to claim 3, which further includes: means for passing wash liquid, at least, along said portion of said conduit intermediate said successive reaction mixtures, and means for actuating said first magnetic means to hold said particulate material for washing by said wash liquid and, subsequently, de-actuating said first magnetic means to release said particulate material into suspension in said wash liquid.

Claim 9

Dependent Claim 84 words

Apparatus according to claim 5, which further includes: means for passing wash liquid, at least, along said portion of said conduit and intermediate said successive reaction mixtures, and wherein said actuating means includes means for actuating said first and second magnetic means concurrently to hold said particulate material for washing by said wash liquid and, subsequently, for selectively de-actuating said first magnetic means to release said particulate material held thereby into suspension in said wash liquid and be carried to said second magnetic means.

Claim 10

Dependent Claim 31 words

Apparatus according to claim 4, wherein each of said first and second magnetic means, when actuated, provide magnetic fields substantially transverse of the direction of reaction mixture flow in said conduit.

Claim 11

Dependent Claim 15 words

Apparatus according to claim 4, wherein each said first and second magnetic means is electromagnetic.

Claim 12

Dependent Claim 19 words

Apparatus according to claim 10, which further includes: means for degaussing each of said first and second magnetic means.

Claim 13

Dependent Claim 38 words

Apparatus according to claim 1, which further includes: means for successively flowing said reaction mixtures along said conduit, and means for introducing an occluding inert fluid segment intermediate successive reaction mixtures to maintain said successive reaction mixtures discrete.

Claim 14

Dependent Claim 26 words

Apparatus according to claim 12, which further includes: means for introducing additional occluding inert fluid segments into said conduit to sub-divide each of said reaction mixtures.

Claim 15

Dependent Claim 43 words

Apparatus according to claim 12, which further includes: means for providing a wash liquid segment between successive reaction mixtures flowing in said conduit, each of said reaction mixtures being separated from adjacent wash liquid segments by at least an occluding inert fluid segment.

Claim 16

Dependent Claim 31 words

Apparatus according to claim 1, which further includes: means for passing successive fluid samples along said conduit, and means for introducing said particulate material into said conduit on an intermittent basis.

Claim 17

Dependent Claim 45 words

Apparatus according to claim 15, which further includes: a source of said particulate material, and wherein said intermittent introducing means includes means for continuously pumping said particulate material from said source and for returning to said source said particulate material not admitted to said conduit.

Claim 18

Dependent Claim 32 words

Apparatus according to claim 15, which further includes: means for introducing buffer solution into said conduit alternately with said particulate material, so as to maintain the flow along said conduit substantially constant.

Claim 19

Dependent Claim 51 words

Apparatus according to claim 3, which further includes: means upstream of said portion of said conduit for detecting the passage of each of said reaction mixtures along said conduit, and means responsive to said detecting means for actuating said magnetic means to trap said particulate material in each said reaction mixture.

Claim 20

Dependent Claim 20 words

Apparatus according to claim 1, which further includes: means for providing a second reagent in each of said reaction mixtures.

Claim 21

Dependent Claim 25 words

Apparatus according to claim 1, which further includes: means for introducing a second reagent into admixture with each said reaction mixture flowing along said conduit.

Claim 22

Dependent Claim 33 words

Apparatus according to claim 1, further including, downstream of said trapping means, valving means in said conduit for selectively directing said separated solid phase or said separated liquid phase to said determining means.

Claim 23

Dependent Claim 18 words

Apparatus according to claim 1, wherein said determining means includes means for measuring radioactively, color, fluorescence or luminescence.

Claim 24

Independent Claim 156 words

A method of analyzing a plurality of fluid samples for particulate constituents of interest, which comprises the steps of: (a) forming a reaction mixture of each of said fluid samples, each reaction mixture comprising a liquid phase and a solid phase, said solid phase comprising a first reagent bound to magnetically attractable particulate material and reactive with the particular constituent to be analyzed in each said fluid sample to form a reaction product, at least on said particulate material; (b) flowing each said reaction mixture in turn and on a discrete basis along a conduit; (c) magnetically trapping said particulate material in each said reaction mixture during flow along a first portion of said conduit, so as to hold said particulate material and thereby separate said solid phase from said liquid phase; and (d) determining the constituent of interest in each said sample by selective analysis of said separated solid phase and/or said separated liquid phase.

Claim 25

Independent Claim 156 words

A method of analyzing a plurality of fluid samples for particulate constituents of interest, which comprises the steps of: (a) forming a reaction mixture of each of said fluid samples, each reaction mixture comprising a liquid phase and a solid phase, said solid phase comprising a first reagent bound to magnetically attractable particulate material and reactive with the particular constituent to be analyzed in each said fluid sample to form a reaction product, at least on said particulate material; (b) flowing each said reaction mixture in turn and on a discrete basis along a conduit; (c) magnetically trapping said particulate material in each said reaction mixture during flow along a first portion of said conduit, so as to hold said particulate material and thereby separate said solid phase from said liquid phase; and (d) determining the constituent of interest in each said sample by selective analysis of said separated solid phase and/or said separated liquid phase.

Claim 26

Dependent Claim 25 words

A method according to claim 23, further comprising the step of: introducing said solid phase along said conduit into admixture with each said fluid sample.

Claim 27

Dependent Claim 28 words

A method according to claim 23, further comprising the step of passing wash liquid along, at least, said first portion of said conduit while trapping said particulate material.

Claim 28

Dependent Claim 20 words

A method according to claim 25, further comprising the step of: re-suspending said trapped particulate material into said wash liquid.

Claim 29

Dependent Claim 68 words

A method according to claim 26 wherein, said re-suspended particulate material is carried to a second portion of said conduit downstream of said first portion, and further comprising the steps of: magnetically trapping said particulate material at said second portion of said conduit, passing wash liquid along said second portion of said conduit while trapping said particulate material, and re-suspending said trapped particulate matter into said wash liquid.

Claim 30

Dependent Claim 23 words

A method according to claim 23, further comprising the steps of: releasing said trapped particulate material, and separately collecting said released particulate matter.

Claim 31

Dependent Claim 37 words

A method according to claim 23, wherein said particulate material is trapped using at least one or more electromagnetic means, and comprising the further step of: degaussing said electromagnetic means upon release of said trapped particulate material.

Claim 32

Dependent Claim 41 words

A method according to claim 23, comprising the further step of: passing said reaction mixtures successively along said conduit, and introducing at least an occluding inert fluid segment intermediate successive reaction mixtures, so as to maintain said successive reaction mixtures discrete.

Claim 33

Dependent Claim 32 words

A method according to claim 30, comprising the further step of: introducing additional occluding inert fluid segments into said conduit to split each of said reaction mixtures into two or more segments.

Claim 34

Dependent Claim 41 words

A method according to claim 30, comprising the further step of: providing a wash liquid segment between successive reaction mixtures in said conduit, each said reaction mixture being separated from adjacent was liquid segments by at least an inert fluid segment.

Claim 35

Dependent Claim 29 words

A method according to claim 30, comprising the further step of: introducing said particulate material into said conduit on an intermittent basis to merge with said successive fluid samples.

Claim 36

Dependent Claim 30 words

A method according to claim 33, comprising the further step of: introducing buffer solution into said conduit alternately with said particulate material to maintain flow along said conduit substantially constant.

Claim 37

Dependent Claim 20 words

A method according to claim 30, comprising the further step of: providing a second reagent into each said reaction mixture.

Claim 38

Dependent Claim 27 words

A method according to claim 35, further including the step of: introducing said second reagent into admixture with each of said fluid samples flowing along the conduit.

Claim 39

Dependent Claim 14 words

Apparatus according to claim 1, wherein the fluid samples are human or animal samples.

Claim 40

Dependent Claim 17 words

Apparatus according to claim 37, wherein the constituent of interest is an antigen, antibody, or antigen:antibody complex.

Claim 41

Dependent Claim 41 words

Apparatus according to claim 19, wherein said constituent of interest is an antigen, said first reagent is an antibody to said antigen, and said second reagent is an antigen which can bind with the antibody and which carries an indentifying label.

Claim 42

Dependent Claim 46 words

Apparatus according to claim 19, wherein said constituent of interest is an antibody, said first reagent is an antigen capable of binding with said antibody, and said second reagent is an antibody which is capable of binding with said antigen and which carries an identifying label.

Claim 43

Dependent Claim 24 words

Apparatus according to claim 39, wherein the said label is a radioactive atom, a fluorescent group, an enzyme or co-enzyme, or a chemiluminescent material.

Claim 44

Dependent Claim 43 words

Apparatus according to claim 19, wherein said second reagent comprises a predetermined amount of substance which reacts with said constituent of interest to form therewith a complex, and wherein said first reagent binds with the said complex or with excess unreacted second reagent.

Claim 45

Dependent Claim 13 words

Apparatus according to claim 19, wherein said second reagent carries a radioactive label.

Claim 46

Dependent Claim 20 words

Apparatus according to claim 1, wherein said first reagent bound to said particulate material is a virus or an immunoglobulin.

Claim 47

Dependent Claim 14 words

Apparatus according to claim 1, wherein said particulate material is of a composite structure.

Claim 48

Dependent Claim 16 words

Apparatus according to claim 45, wherein said particulate material comprises a matrix containing magnetically attractable material.

Claim 49

Dependent Claim 19 words

Apparatus according to claim 46, wherein said matrix comprises an organic material capable of binding to said first reagent.

Claim 50

Dependent Claim 20 words

Apparatus according to claim 1, wherein said particulate material has a specific gravity close to that of said reaction mixture.

Claim 51

Dependent Claim 22 words

Apparatus according to claim 48, wherein the specific gravity of said particulate material is substantially in the range of 1.4 to 3.2.

Claim 52

Dependent Claim 24 words

Apparatus according to claim 40, wherein the said label is a radioactive atom, a fluorescent group, an enzyme or co-enzyme, or a chemiluminescent material.

Claim 53

Independent Claim 132 words

A method of analyzing a plurality of fluid samples for particular constituents of interest, which comprises the steps of: (a) forming a reaction mixture of each of said fluid samples, said reaction mixture comprising magnetically attractable particulate material and a reagent reactive with a particular constituent to be analyzed to form a reaction product, at least a portion of said reaction product being bound to said particulate material; (b) flowing each said reaction mixture in turn and on a discrete basis along a conduit; (c) magnetically trapping said particulate material in each said reaction mixture along a portion of said conduit, so as to separate said particulate material from said reaction mixture; and (d) determining said constituent of interest by selective analysis of said separated particulate material and/or said separated reaction mixture.

Claim 54

Independent Claim 132 words

A method of analyzing a plurality of fluid samples for particular constituents of interest, which comprises the steps of: (a) forming a reaction mixture of each of said fluid samples, said reaction mixture comprising magnetically attractable particulate material and a reagent reactive with a particular constituent to be analyzed to form a reaction product, at least a portion of said reaction product being bound to said particulate material; (b) flowing each said reaction mixture in turn and on a discrete basis along a conduit; (c) magnetically trapping said particulate material in each said reaction mixture along a portion of said conduit, so as to separate said particulate material from said reaction mixture; and (d) determining said constituent of interest by selective analysis of said separated particulate material and/or said separated reaction mixture.

Claim 55

Dependent Claim 65 words

A method as defined in claim 51, including the further steps of: passing said fluid samples along said conduit on a successive basis, separating successive fluid samples by at least an inert fluid segment, so as to maintain said fluid samples discrete, and introducing said reagent and said particulate material on an intermittent basis to merge with said fluid samples to form said reaction mixtures.

Claim 56

Dependent Claim 29 words

A method as defined in claim 51, comprising the further step of: forming said particulate material to have a specific gravity substantially equal to that of said reaction mixture.

Claim 57

Dependent Claim 41 words

A method according to claim 51, comprising the further steps of: passing said reaction mixtures successively along said conduit, and introducing, at least, an occluding inert fluid segment intermediate successive reaction mixtures, so as to maintain said successive reaction mixtures discrete.

Claim 58

Dependent Claim 40 words

A method according to claim 51, comprising the further step of: providing a wash liquid segment between said successive reaction mixtures, each of said reaction mixtures being separated from adjacent wash liquid segments by at least an inert fluid segment.

Claim 59

Dependent Claim 33 words

A method according to claim 51, comprising the further step of: maintaining said particulate material magnetically trapped during passages of at least a portion of said wash liquid segment along said conduit portion.

Claim 60

Dependent Claim 86 words

A particulate material for use in the analysis of a liquid sample of known specific gravity, said particulate material comprising a reagent and one or more magnetic particles in a matrix of binding material, said particulate material having a controlled specific gravity approaching that of said liquid sample so as to retard separation of said particulate material when mixed with said liquid sample, said binding material being selected from a group consisting of: cellulose or a cellulose derivative, a polymer or synthetic polymeric material, and agarose.

Claim 61

Dependent Claim 86 words

A particulate material for use in the analysis of a liquid sample of known specific gravity, said particulate material comprising a reagent and one or more magnetic particles in a matrix of binding material, said particulate material having a controlled specific gravity approaching that of said liquid sample so as to retard separation of said particulate material when mixed with said liquid sample, said binding material being selected from a group consisting of: cellulose or a cellulose derivative, a polymer or synthetic polymeric material, and agarose.

Claim 62

Dependent Claim 19 words

The particulate material of claim 57, wherein said specific gravity of said particulate material is approximately equal to 1.4.

Claim 63

Dependent Claim 26 words

The particulate material of claim 57, wherein the magnetic particles are selected from a group consisting of iron, magnetic iron oxides, nickel, cobalt or chromium oxide.

Claim 64

Dependent Claim 23 words

The particulate material of claim 57, wherein said reagent is selected from a group consisting of an antigen, an antibody or biological substance.

Claim 65

Dependent Claim 24 words

The particulate material of claim 57, wherein said reagent is an antigen and said liquid sample comprises an antibody for reaction with said antigen.

Claim 66

Dependent Claim 24 words

The particulate material of claim 57, wherein said reagent is an antibody and said liquid sample comprises an antigen for reaction with said antibody.

Claim 67

Independent Claim 111 words

A method of immunoassaying a sample, comprising the steps of: mixing: (a) a sample defining a liquid phase, and (b) a reagent combined with a magnetically attractable particulate defining a solid phase, forming said solid phase to have a specific gravity so as to tend to be suspended within said liquid phase upon mixing of said phases, such that separation of the two phases is retarded and reactivity of the sample with said reagent is enhanced, magnetically separating said liquid and said solid phases following reaction of said sample with said reagent, and measuring a reaction product of said sample and said reagent in said separated solid and/or said liquid phase.

Claim 68

Independent Claim 111 words

A method of immunoassaying a sample, comprising the steps of: mixing: (a) a sample defining a liquid phase, and (b) a reagent combined with a magnetically attractable particulate defining a solid phase, forming said solid phase to have a specific gravity so as to tend to be suspended within said liquid phase upon mixing of said phases, such that separation of the two phases is retarded and reactivity of the sample with said reagent is enhanced, magnetically separating said liquid and said solid phases following reaction of said sample with said reagent, and measuring a reaction product of said sample and said reagent in said separated solid and/or said liquid phase.

Claim 69

Dependent Claim 29 words

The method of claim 63, comprising the further step of forming said solid phase to have a specific gravity approximately equal to the specific gravity of said liquid phase.

Claim 70

Dependent Claim 23 words

The method of claim 63, comprising the further step of forming said solid phase to have a specific gravity approximately equal to 1.4.

Claim 71

Dependent Claim 27 words

The method of claim 63, wherein said reagent is an antigen, and comprising the step of combining an antibody with said particulate to define said solid phase.

Claim 72

Dependent Claim 28 words

The method of claim 63, wherein said reagent is an antibody, and comprising the further step of combining an antigen with said particulate to define said solid phase.

Annuity Stage	Window Opens	Payment Deadline	Surcharge Period Until	Estimated Fee	Status
3.5 Years (Year 4)	1982-02-26	1982-08-28	1983-02-27	$2000.00	Window Closed / Lapsed
7.5 Years (Year 8)	1986-02-26	1986-08-28	1987-02-27	$3760.00	Window Closed / Lapsed
11.5 Years (Year 12)	1990-02-26	1990-08-28	1991-02-27	$7700.00	Window Closed / Lapsed

Automatic apparatus and method for the assay of fluid samples

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