Apparatus and methods for carrying out electrochemiluminescence test measurements

Abstract

Apparatus for the conduct of electrochemiluminescence measurements includes an ECL chamber having a transparent window defining one wall of the chamber and a photodetector mounted closely adjacent thereto. An assay fluid is subject to a magnetic field and is electrically energized. Electrochemiluminescence induced in the fluid is measured by the photodetector.

What is claimed is:  
     
         1 . An apparatus for the conduct of electrochemiluminescence measurements comprising: 
 a cell having at least one cell wall which includes a transparent portion adjacent to an ECL chamber defined within said cell;    a working electrode abutting said ECL chamber and in optical registration with said transparent portion;    a counter electrode abutting said ECL chamber; and    an electrically-shielded window adjacent to and in optical registration with said transparent portion.    
     
     
         2 . The apparatus according to  claim 1  further comprising a photodetector.  
     
     
         3 . The apparatus according to  claim 1  further comprising a photodetector in optical registration with said electrically-shielded window, said transparent portion and said working electrode.  
     
     
         4 . The apparatus according to  claim 3  wherein no air gap exists between any of said photodetector, said electrically-shielded window, and said transparent portion.  
     
     
         5 . The apparatus according to  claim 3  wherein said electrically-shielded window and said transparent portion each has a refractive index of between 1.3 and 1.6.  
     
     
         6 . The apparatus according to  claim 3  wherein more than 40% of any electrochemiluminescence generated within said ECL chamber is incident upon said photodetector.  
     
     
         7 . An apparatus for the conduct of electrochemiluminescence measurements comprising: 
 a cell having at least one cell wall which includes a transparent portion adjacent to an ECL chamber defined within said cell;    a working electrode abutting said ECL chamber and in optical registration with said transparent portion;    a counter electrode abutting said ECL chamber;    a photodiode in optical registration with said transparent portion; and    an optical filter adjacent to and in optical registration with said transparent portion.    
     
     
         8 . The apparatus according to  claim 7  further comprising a shortpass optical filter adjacent to and in optical registration with said transparent portion, for passing light having a wavelength of less than 750 nm  
     
     
         9 . The apparatus according to  claim 7  wherein said optical filter comprises an IR-suppressing filter.  
     
     
         10 . The apparatus according to  claim 7  wherein said optical filter comprises a filter having a first transmittance of 600 nm light and a second transmittance of 1000 nm light, wherein said first transmittance is at least four times greater than said second transmittance.  
     
     
         11 . An apparatus for the conduct of electrochemiluminescence measurements comprising: 
 a cell having at least one cell wall which includes a transparent portion adjacent to an ECL chamber defined within said cell;    a working electrode abutting said ECL chamber and in optical registration with said transparent portion; and    a counter electrode abutting said ECL chamber and having an aperture in optical registration with said transparent portion.    
     
     
         12 . The apparatus according to  claim 11  further comprising a photodetector.  
     
     
         13 . An apparatus for the conduct of electrochemiluminescence measurements comprising: 
 a cell having at least one cell wall which includes a transparent portion adjacent to an ECL chamber defined within said cell;    a working electrode abutting said ECL chamber and in optical registration with said transparent portion; and    a counter electrode abutting said ECL chamber;    wherein said working electrode is removably fitted within said cell and has a planar electrode surface abutting said ECL chamber.    
     
     
         14 . The apparatus according to  claim 13  further comprising a photodetector.  
     
     
         15 . The apparatus according to  claim 13  further comprising a gasket interposed between said working electrode and said counter electrode, said gasket abutting said ECL chamber, said working electrode, and said counter electrode.  
     
     
         16 . An apparatus for the conduct of electrochemiluminescence measurements comprising: 
 a cell having at least one cell wall which includes a transparent portion adjacent to an ECL chamber defined within said cell;    a working electrode having a planar electrode surface abutting said ECL chamber and in optical registration with said transparent portion of said cell wall, said working electrode being positioned within the cell such that no seam between said working electrode and said cell abuts said ECL chamber; and    a counter electrode abutting said ECL chamber.    
     
     
         17 . The apparatus according to  claim 16  further comprising a photodetector.  
     
     
         18 . The apparatus according to  claim 16  further comprising a gasket interposed between said working electrode and said counter electrode, said gasket abutting said ECL chamber, said working electrode, and said counter electrode.  
     
     
         19 . An apparatus for the conduct of electrochemiluminescence measurements comprising: 
 a cell having at least one cell wall which includes a transparent portion adjacent to an ECL chamber defined within said cell;    a working electrode abutting said ECL chamber and in optical registration with said transparent portion;    a counter electrode abutting said ECL chamber;    a photodiode adjacent to and in optical registration with said transparent portion; and    a magnetic field generating device operable to apply a magnetic field at said working electrode.    
     
     
         20 . The apparatus according to  claim 19  wherein said magnetic field generating device applies said magnetic field while electrochemiluminescence is induced in an assay fluid in said ECL chamber.  
     
     
         21 . The apparatus according to  claim 19  wherein said magnetic field generating device applies said magnetic field while electrochemiluminescence is induced in an assay fluid flowing through said ECL chamber.  
     
     
         22 . An apparatus for the conduct of electrochemiluminescence measurements comprising: 
 a cell having at least one cell wall which includes a transparent portion adjacent to an ECL chamber defined within said cell;    a working electrode abutting said ECL chamber and in optical registration with said transparent portion;    a counter electrode abutting said ECL chamber; and    a photodiode adjacent to and in optical registration with said transparent portion, said photodiode having a detection sensitivity substantially limited to light having a wavelength in a range of 400 nm to 900 nm.    
     
     
         23 . An apparatus for the conduct of electrochemiluminescence measurements comprising: 
 a cell having at least one cell wall which includes a transparent portion adjacent to an ECL chamber defined within said cell;    a working electrode abutting said ECL chamber and in optical registration with said transparent portion;    a counter electrode abutting said ECL chamber and having an aperture in optical registration with said transparent portion;    a photodetector adjacent to and in optical registration with said transparent portion; and,    a magnetic field generating device in registration with said aperture, operable to apply a magnetic field to said working electrode.    
     
     
         24 . The apparatus according to  claim 23  wherein said photodetector comprises a photodiode.  
     
     
         25 . An apparatus for the conduct of electrochemiluminescence measurements comprising: 
 a cell having at least one cell wall which includes a transparent portion adjacent to an ECL chamber defined within said cell;    a working electrode abutting said ECL chamber and in optical registration with said transparent portion;    a counter electrode abutting said ECL chamber;    a photodiode adjacent to and in optical registration with said transparent portion;    a magnetic field generating device operable to apply a magnetic field to said working electrode; and    a magnetic field detector in registration with said magnetic field generating device.    
     
     
         26 . The apparatus according to  claim 25  wherein said magnetic field generating device further comprises an actuator operable to move said magnetic field generating device so as to selectably apply said magnetic field to said working electrode; and 
 wherein said magnetic field detector determines a position of said movable magnet device means by detecting said magnetic field.  
 
     
     
         27 . An apparatus for the conduct of electrochemiluminescence measurements comprising: 
 a cell having at least one cell wall which includes a transparent portion adjacent to an ECL chamber defined within said cell;    a working electrode abutting said ECL chamber and in optical registration with said transparent portion;    a counter electrode abutting said ECL chamber;    a photodiode, adjacent to and in optical registration with said transparent portion, for detecting electrochemiluminescence induced in an assay fluid in said ECL chamber and for producing an ECL signal representative of an intensity of said electrochemiluminescence;    a storage device, coupled to said photodiode, in which a calibration signal representative of a calibration electrochemiluminescence may be stored; and    a processor coupled to said photodiode and to said storage device operable to calculate a corrected signal as a function of said ECL signal and said calibration signal.    
     
     
         28 . A cell for the conduct of electrochemiluminescence measurements comprising: 
 a first base having a first interior surface;    a planar working electrode positioned on said first interior surface;    a second base having a second interior surface and having a transparent portion therein to allow light to pass therethrough;    a planar counter electrode positioned on said second interior surface, said counter electrode having at least one opening therein to allow said light to pass therethrough in registration with said working electrode and said transparent portion of said second base;    a gasket positioned between said working electrode and said counter electrode to define therebetween a cell volume, said volume communicating with the opening in said counter electrode; and    a retaining device, coupled to the bases; wherein the interior surfaces of the bases are in opposing relationship to form said cell; and    wherein said second base includes a conduit through which fluid may be introduced into and removed from said cell volume.    
     
     
         29 . A cell for the conduct of electrochemiluminescence including cell structural elements, a working electrode and a counter electrode, at least one of said structural elements having a transparent portion therein, wherein said working electrode is mounted on an interior surface of a said structural element, a portion of said working electrode and the transparent portion of said at least one structural element defining, at least in part, a chamber for the conduct of electrochemiluminescence, the working electrode comprising the entirety of a continuous planar surface of said chamber and said portion of said working electrode and the transparent portion of said structural element being optically in registration with one another.  
     
     
         30 . A method for conducting an ECL measurement comprising the steps of: 
 introducing an assay sample into an ECL chamber within a flow cell;    simultaneously applying an electric field and a magnetic field to said assay sample in said ECL chamber; and    measuring, through an electrically-shielded window defining a wall of said ECL chamber, electrochemiluminescence induced in said assay fluid in said ECL chamber while said electric field and said magnetic field are applied.    
     
     
         31 . The method according to  claim 30  wherein said electric field and said magnetic field are applied, and electrochemiluminescence is measured, while said assay sample flows through said ECL chamber.  
     
     
         32 . The method according to  claim 30  wherein said magnetic field collects at a working electrode within said flow cell a plurality of magnetic particles from said assay sample fluid.  
     
     
         33 . A method for conducting an ECL measurement comprising the steps of: 
 introducing an assay sample into an ECL chamber within a flow cell;    simultaneously applying an electric field and a magnetic field to said assay sample in said ECL chamber; and    measuring with a semiconductor photodetector electrochemiluminescence induced in said assay fluid in said ECL chamber while said electric field and said magnetic field are applied.    
     
     
         34 . The method according to  claim 33  wherein said step of measuring further comprises the step of measuring electrochemiluminescence through an electrically-conductive material interposed between said semiconductor photodetector and said ECL chamber.  
     
     
         35 . The method according to  claim 33  wherein said electric field and said magnetic field are applied, and electrochemiluminescence is measured, while said assay sample flows through said ECL chamber.  
     
     
         36 . The method according to  claim 33  wherein said magnetic field collects at a working electrode within said flow cell a plurality of magnetic particles from said assay sample fluid.  
     
     
         37 . A method for normalizing a plurality of ECL modules comprising the steps of: 
 conducting an ECL measurement with a reference ECL module upon a reference sample to produce a reference ECL signal;    conducting an ECL measurement with a test, ECL module upon said reference sample to produce a test ECL signal; and    calculating a correction transform function as a function of said reference ECL signal and said test ECL signal.    
     
     
         38 . The method according to  claim 37  further comprising the step of applying said correction transform function to another ECL signal produced by said test ECL measurement instrument.  
     
     
         39 . The method according to  claim 37  further comprising the step of adjusting an operation of said test ECL module as a function of said correction transform function.  
     
     
         40 . The method according to  claim 37  further comprising the step of storing said correction transform function.  
     
     
         41 . An apparatus for the conduct of assay measurements comprising: 
 a cell having at least one cell wall which includes a transparent portion adjacent to an ECL chamber defined within said cell;    a working electrode abutting said ECL chamber and in optical registration with said transparent portion;    a counter electrode abutting said ECL chamber;    a first light detector, optically coupled to said ECL chamber and in optical registration with said transparent portion, for detecting electrochemiluminescence induced within said ECL chamber; and    a light source, optically coupled to said ECL chamber, for providing light to said ECL chamber.    
     
     
         42 . The apparatus according to  claim 41  further comprising a second light detector optically coupled to said ECL chamber and operable to detect light from said light source.  
     
     
         43 . The apparatus according to  claim 41  further comprising a second light detector optically coupled to said ECL chamber and operable to detect a luminescence generated within said cell.  
     
     
         44 . The apparatus according to  claim 41  further comprising a wavelength selection device, coupled to said light source, for selecting the wavelength of light provided to said ECL chamber.  
     
     
         45 . An assay system comprising: 
 a plurality of ECL modules; and    a controller coupled to each of said plurality of ECL modules and operable to control an operation of each of said plurality of ECL modules.    
     
     
         46 . The apparatus according to  claim 45  wherein said controller comprises a microcontroller.  
     
     
         47 . The apparatus according to  claim 45  further comprising a user interface coupled to said controller.  
     
     
         48 . An assay system comprising: 
 a plurality of ECL modules; and    a power supply coupled to each of said plurality of ECL modules and operable to supply electrical power to each of said plurality of ECL modules.    
     
     
         49 . An assay system comprising: 
 a plurality of ECL modules; and    a sample introduction device coupled to each of said plurality of ECL modules and operable to supply a sample to each of said plurality of ECL modules.    
     
     
         50 . The apparatus according to  claim 49  wherein each of said plurality of ECL modules receives a different sample from said sample introduction device.  
     
     
         51 . The apparatus according to  claim 49  wherein said sample introduction device comprises at least one valve.  
     
     
         52 . The apparatus according to  claim 49  wherein said sample introduction device comprises at least one reagent container.  
     
     
         53 . The apparatus according to  claim 49  wherein said sample introduction device comprises a cartridge port coupled to each of said plurality of ECL modules.  
     
     
         54 . The apparatus according to  claim 53  wherein said sample introduction device further comprises an assay sample cartridge adapted for removable coupling with said cartridge port.  
     
     
         55 . An assay system comprising: 
 a plurality of ECL modules; and    a waste handling device coupled to each of said plurality of ECL modules and operable to receive waste from each of said plurality of ECL modules.    
     
     
         56 . The apparatus according to  claim 55  wherein said waste handling device comprises at least one valve.  
     
     
         57 . An assay system comprising: 
 a temperature-controlled enclosure; and    a plurality of ECL modules positioned within said temperature-controlled enclosure.    
     
     
         58 . An assay system comprising: 
 an ECL module having an assay fluid outlet; and    an assay module having an assay fluid inlet coupled to said assay fluid outlet.    
     
     
         59 . An assay system comprising: 
 an assay module having an assay fluid outlet; and    an ECL module having an assay fluid inlet coupled to said assay fluid outlet.    
     
     
         60 . An assay system comprising: 
 an ECL module having a first assay fluid inlet and a first waste fluid outlet; and    an assay module having a second assay fluid inlet coupled to said first assay fluid inlet and having a second waste fluid outlet coupled to said first waste fluid outlet.    
     
     
         61 . A modular ECL assay subsystem adapted for connection to and use with a power supply, a controller, and a fluid exchange system common to a plurality of said modular ECL subsystems comprising: 
 a cell having at least one cell wall which includes a transparent portion adjacent to an ECL chamber defined within said cell;    a working electrode abutting said ECL chamber and in optical registration with said transparent portion;    a counter electrode abutting said ECL chamber;    a light detector, optically coupled to said ECL chamber, for detecting electrochemiluminescence induced within said ECL chamber;    a waveform generator coupled to at least one of said working electrode and said counter electrode and operable to generate an electric signal;    a subsystem controller coupled to said waveform generator and operable to for control an operation of said waveform generator; and    an interface to said cell, coupled to each of the subsystem controller said power supply, said controller, and said fluid exchange system, said controller being operable to control said subsystem controller said power supply being operable to supply electrical power to said subsystem controller and said fluid exchange system being operable to provide an assay fluid to said cell and to receive a waste fluid from said cell.    
     
     
         62 . An integrated ECL assay system comprising: 
 a plurality of ECL modules wherein each of the modules comprises a flow cell, a magnet controller, a main controller, and a main interface;    a system controller, coupled to each of said plurality of ECL modules via a respective main interface; and    a chassis, removably coupled to each of said plurality of ECL modules and to said system controller.    
     
     
         63 . The integrated ECL assay system according to  claim 62  wherein at least one of said plurality of ECL modules further comprises a heater and a temperature controller.  
     
     
         64 . The integrated ECL assay system according to  claim 62  wherein at least one of said plurality of ECL modules further comprises a magnet detector.  
     
     
         65 . The integrated ECL assay system according to  claim 62  wherein at least one of said plurality of ECL modules further comprises an amplifier.  
     
     
         66 . An assay system comprising: 
 an ECL module;    an assay module; and    a sample introduction device coupled to each of said ECL and assay modules and operable to supply a sample to each of said ECL and assay modules.    
     
     
         67 . The assay system of  claim 72  wherein said assay module is selected from the group consisting of a blood gasses module, a blood electrolytes module, a binding assay module, enzymatic assay module, fluorescence assay module, colorometric assay module, chemiluminescence assay module, biosensor module, hematocrit module; hematology module, coagulation module and electrochemical assay module.  
     
     
         68 . The apparatus according to claim  73  wherein each of said ECL and assay modules receives a different sample from said sample introduction device.  
     
     
         69 . The apparatus according to claim  73  wherein said sample introduction device comprises at least one valve.  
     
     
         70 . The apparatus according to claim  73  wherein said sample introduction device comprises at least one reagent container.  
     
     
         71 . The apparatus according to claim  73  wherein said sample introduction device comprises a cartridge port coupled to each of said ECL and assay modules.  
     
     
         72 . The apparatus according to claim  77  wherein said sample introduction device further comprises an assay sample cartridge adapted for removable coupling with said cartridge port.