Arrays of microparticles and methods of preparation thereof

Abstract

This invention provides high unit density arrays of microparticles and methods of assembling such arrays. The microparticles in the arrays may be functionalized with chemical or biological entities specific to a given target analyte. The high unit density arrays of this invention are formed on chips which may be combined to form multichip arrays according to the methods described herein. The chips and/or multichip arrays of this invention are useful for chemical and biological assays.

We claim: 
     
         1 . A system for performing bioassays, said system comprising at least one biochip, wherein at least one biochip comprises a patterned chip and a plurality of bio-functionalized, optically encoded beads affixed thereto. 
     
     
         2 . A method for producing biochips comprising patterning a substrate to form a plurality of chip regions, partially scribing between the chip regions, assembling at least one bead array comprising bio-functionalized, optically encoded beads on a surface of the wafer in at least one chip region; and singulating the wafer to form individual biochips. 
     
     
         3 . A method of performing bioassays comprising contacting a plurality of biochips bonded to a carrier with a solution comprising at least one target analyte, and detecting the target analyte. 
     
     
         4 . The method according to  claim 3 , wherein the plurality of biochips comprises at least two subpopulations of biochips with differently biofunctionalized arrays. 
     
     
         5 . The method according to  claim 3 , wherein the plurality of biochips comprises at least two subpopulations of biochips, wherein the biochips of the different sub-populations are different sizes. 
     
     
         6 . The method according to  claim 3 , wherein the plurality of biochips comprises at least two subpopulations of biochips with different bead array geometries. 
     
     
         7 . The method according to  claim 3 , wherein the plurality of biochips comprises at least two subpopulations with at least two characteristics taken from the group of characteristics consisting of differently biofunctionalized arrays, different sizes, and different bead array geometries. 
     
     
         8 . A bead array comprising a removable coating for protecting said bead array on a biochip, said bead array comprising a plurality of beads with surfaces to which molecular probes are attached, and said coating having the property of being non-reactive towards the molecular probes on the surfaces of the beads. 
     
     
         9 . The method according to  claim 3 , wherein the biochips comprise a semiconductor substrate with a patterned dielectric film on at least one surface of said semiconductor substrate, and wherein the pattern of the dielectric film comprises a star-shape, and wherein detecting the analyte comprises the step of using LEAPS. 
     
     
         10 . A process for directly depositing beads on a surface of a semiconductor substrate to form a bead array, said process comprising adding a solution of beads to the surface of a patterned semiconductor substrate containing structures for restraining the beads and mechanically agitating the solution to induce the beads to settle in the structures. 
     
     
         11 . A method of making an assay device comprising a plurality of biofunctionalized molecular probes, said method comprising affixing molecular probes specific for a target analyte from a probe library to a plurality of beads to form a bead sub-population, affixing at least one bead sub-population to a major surface of a wafer comprised of chip regions that possess a decodable tag that identifies the wafer of origin, singulating the wafer to produce a plurality of biochips, repeating the process with at least one other bead sub-population molecular probes specific for a different target analyte, and assembling the biochips to form a said assay device comprising a biochip array. 
     
     
         12 . The assay device produced according to the method of  claim 11 . 
     
     
         13 . A method of performing an assay using the assay device according to  claim 11  comprising contacting the biochip array to a solution containing at least one target analyte and detecting the reaction products. 
     
     
         14 . A method for fabricating a carrier for biochips comprising covering a solid substrate that has at least one hydrophilic major surface with a patterned hydrophobic layer, said patterned hydrophobic layer spatially defining an array of biochips. 
     
     
         15 . A method for quality control during fabrication of a biochip, said method comprising optically encoding bio-functionalized beads, exposing a patterned substrate containing recesses for restraining beads to a solution containing said beads, and optically imaging the beads to ensure that the recesses are substantially occupied. 
     
     
         16 . A method for recesses holes in a substrate surface, said holes having re-entrant sidewall profiles, comprising etching the substrate to form a recesses with substantially vertical sidewalls and subsequently depositing a layer of material that adheres to the sidewalls to produce re-entrant sidewall profiles. 
     
     
         17 . A method of retaining a population of charged beads in recesses in a surface of a semiconductor comprising depositing a first charged polymer on the surface of the semiconductor, said first charged polymer having a charge of opposite sign to the charged beads, depositing the beads onto the surface of the semiconductor, and depositing a second charged polymer on the surface of the semiconductor, said second charged polymer having a charge of opposite sign to the first charged polymer. 
     
     
         18 . A chip comprising partitions wherein said partitions define a plurality of regions for one or more functionalized beads. 
     
     
         19 . The chip according to  claim 18 , wherein said functionalized beads are optically encoded and biofunctionalized to form a biochip. 
     
     
         20 . A bioarray comprising a plurality of chips, said chips comprising functionalized beads. 
     
     
         21 . The bio-array according to  claim 20 , wherein the functionalized beads are comprised of at least two differently functionalized beads. 
     
     
         22 . A wafer comprising a plurality of chip regions for restraining one or more functionalized beads, said plurality of regions further comprising fractionation regions located on said wafer so as to enable fractionation of said bead restraining regions into subunits, wherein each subunit comprises one or more bead restraining regions. 
     
     
         23 . The wafer according to  claim 22 , wherein the wafer is fractionated at fractionation regions to produce a plurality of chip.