Devices and methods for biochip multiplexing

Abstract

The invention is directed to devices that allow for simultaneous multiple biochip analysis. In particular, the devices are configured to hold multiple cartridges comprising biochips comprising arrays such as nucleic acid arrays, and allow for high throughput analysis of samples.

1 - 14 . (canceled) 
     
     
         15 . A multiplex detection device, comprising:
 a plurality of stations each for housing a biochip and each independently addressable;   a plurality of biochips each in a station and each comprising:
 i) an array of working electrodes at least some of which comprise a capture binding ligand for detecting analyte in an aqueous sample; 
 ii) one or more reference electrodes; 
 iii) one or more auxiliary electrodes; and 
 iv) interconnects for electrical communication with each of said electrodes; 
   
       controls for inputting signal to said electrodes;
 a detector for detecting output signal from said electrodes; 
 one or more pumps for circulating aqueous analyte samples on said biochips; and 
 one or more processors for amplifying analyte signal or filtering background. 
 
     
     
         16 . The device of  claim 15  further comprising one or more of an analog to digital converter and a digital to analog converter. 
     
     
         17 . The device of  claim 15  wherein at least some of said working electrodes comprise a self assembling monolayer. 
     
     
         18 . The device of  claim 17  wherein said self assembling monolayer is a mixed self-assembling monolayer comprising insulators. 
     
     
         19 . The device of  claim 15  comprising different capture binding ligands on different working electrodes. 
     
     
         20 . The device of  claim 15  wherein said biochips further comprise one or more electrochemical detection labels. 
     
     
         21 . The device of  claim 20  comprising a plurality of electrochemical detection labels of different electrochemical potential. 
     
     
         22 . The device of  claim 21  wherein at least some of said electrochemical detection labels of different electrochemical potential are selected from the group consisting of ferrocene and ferrocene derivatives. 
     
     
         23 . The device of  claim 15  wherein at, least one of said capture binding ligands comprises nucleic acids or nucleic acid analogs. 
     
     
         24 . The device of  claim 15  further comprising a plurality of different electrochemical detection labels of different electrochemical potential on each biochip. 
     
     
         25 . The device of  claim 15  comprising a plurality of different nucleic acid capture binding ligands on each biochip. 
     
     
         26 . The device of  claim 15  comprising both nucleic acids and non nucleic acid capture binding ligands. 
     
     
         27 . The device of  claim 15  wherein said biochips further comprise nucleic acid analyte amplification reagents. 
     
     
         28 . A multiplex detection device, comprising:
 a plurality of stations each for housing a biochip and each independently addressable;   a plurality of biochips each in a station and each comprising:
 i) an array of working electrodes at least some of which comprise a capture binding ligand for detecting analyte in an aqueous sample; 
 ii) one or more reference electrodes; 
 iii) one or more auxiliary electrodes; 
 iv) interconnects for electrical communication with each of said electrodes; and 
 v) one or more aqueous buffer or reaction chambers; 
   controls for inputting signal to said electrodes;   a detector for detecting output signal from said electrodes;   one or more pumps for circulating aqueous analyte samples on said biochips; and   one or more processors for amplifying analyte signal or filtering background;   one or more on-chip aqueous buffer or reaction mixture chambers.   
     
     
         29 . A multiplex detection device, comprising:
 a plurality of stations each for housing a biochip and each independently addressable;   a plurality of biochips each in a station and each comprising:
 i) an array of working electrodes at least some of which comprise a capture binding ligand for detecting analyte in an aqueous sample; 
 ii) one or more reference electrodes; 
 iii) one or more auxiliary electrodes; 
 iv) interconnects for electrical communication with each of said electrodes; and 
 v) one or more aqueous buffer or reaction chambers; 
   wherein said plurality of biochips are configured to circulate and recirculate an aqueous analyte sample across said array of working electrodes;   controls for inputting signal to said electrodes;   a detector for detecting output signal from said electrodes;   one or more pumps for circulating aqueous analyte samples on said biochips; and   one or more processors for amplifying analyte signal or filtering background;   one or more on-chip aqueous buffer or reaction mixture chambers.   
     
     
         30 . A multiplex detection device, comprising:
 a plurality of stations each for housing a biochip and each independently addressable;   a plurality of biochips each in a station and each comprising:
 i) an array of working electrodes housed serially in an elongated channel and at least some of which comprise a capture binding ligand for detecting analyte in an aqueous sample; 
 ii) one or more reference electrodes; 
 iii) one or more auxiliary electrodes; 
 iv) interconnects for electrical communication with each of said electrodes; and 
 v) one or more aqueous buffer or reaction chambers; 
   wherein said plurality of biochips are configured to circulate and recirculate an aqueous analyte sample across said array of working electrodes;   controls for inputting signal to said electrodes;   a detector for detecting output signal from said electrodes;   one or more pumps for circulating aqueous analyte samples on said biochips; and   one or more processors for amplifying analyte signal or filtering background;   
     
     
         31 . A multiplex detection device, comprising:
 a plurality of stations each for housing a biochip and each independently addressable;   a plurality of biochips each in a station and each comprising:
 i) an array of working electrodes at least some of which comprise a capture binding ligand for detecting analyte in an aqueous sample; 
 ii) one or more reference electrodes; 
 iii) one or more auxiliary electrodes; and 
 iv) interconnects for electrical communication with each of said electrodes; 
   controls for inputting signal to said electrodes;   a detector for detecting output signal from said electrodes;   one or more pumps for circulating aqueous analyte samples on said biochips;   one or more processors for amplifying analyte signal or filtering background; and   thermocontrols for controlling the temperature of said biochips.   
     
     
         32 . The device of  claim 15  wherein at least one of said analytes or capture binding ligands is associated with a genetic or infectious disease. 
     
     
         33 . The device of  claim 23  wherein said nucleic acid analog has a positively charged backbone. 
     
     
         34 . The device of  claim 15  wherein said biochips further comprise nucleic acid signal probes bearing electrochemical detection labels. 
     
     
         35 . The device of  claim 15  wherein each of said plurality of biochips further comprises a memory chip or barcode and wherein said device further comprises a memory chip or barcode reader. 
     
     
         36 . The device of  claim 15  wherein said plurality of biochips are configured to receive and process an aqueous sample selected from the group consisting of blood, tissue, sputum and saliva. 
     
     
         37 . The device of  claim 15  wherein said analyte or analytes is present in the form of an aqueous sample and wherein said device further comprises mixing means selected from the group consisting of piezoelectric mixing, thermal gradients, bubble pump mixer, and acoustic streaming to facilitate distribution of said analyte or analytes to said working electrodes. 
     
     
         38 . The device of  claim 15  further comprising digital lock-in means and a program for performing one or more of a Fourier transform and joint time-frequency transformation to analyze detection results. 
     
     
         39 . The device of  claim 15  further comprising means for measuring one or more of a frequency, amplitude, phase shift, DC offset voltage, and faradaic impedance response.