Method for Producing an Array of Planar Microparticles with Surface Molecular Multiplexing, Resulting Array and Use Thereof

Abstract

A method for controlled production of an array of planar microparticles with the multiplexing of molecules on the surface thereof, intended to function as molecular sensors and/or actuators and a matrix (array) of microparticles, the surface thereof being printed with all of the molecular components required to provide the surface with functionality. Different molecular elements are multiplexed on the surface of each particle while they are supported on a substrate by means of a structural foot engraved below the particle. These microparticles can be released mechanically from the support on which they are produced using a controlled mechanical rupture method which is not chemically aggressive and therefore does not affect the molecules previously printed on the surface. The array and the particles contained therein offer great versatility in both chemical and/or biological applications.

1 . A method for producing an array of planar microparticles with functionalized surfaces, said method comprising:
 a) preparing a structuration layer of a microparticle starting material on top of a substrate that serves as a support;   b) shaping the microparticles in the structuration layer by using a microelectronic lithography technique that shapes a geometry and lateral dimensions, and an engraving technique with which a thickness of the microparticles is defined;   c) forming a foot in an upper part of the substrate that is found under the structuration layer in order to support each microparticle using engraving techniques; and   d) chemically functionalizing the surface of the microparticles that are supported upon the substrate by the feet using one or more molecular components.   
     
     
         2 . The method according to  claim 1 , wherein the substrate is formed of a single material, said material being a silicon sheet or by two materials, including a second material in the form of a layer that is located in the upper part of the substrate beneath the microparticle structuration layer. 
     
     
         3 . (canceled) 
     
     
         4 . The method according to  claim 1 , wherein the structuration layer of the microparticles is a material selected from the group consisting of polycrystalline silicon, silicon oxide, nitride selected from the group consisting of silicon, gold, platinum, copper, aluminum, nickel, cobalt, chromium, metal oxides; tantalum, iron and aluminum silicates; and silicide selected from the group consisting of tantalum silicide, iron silicide and aluminum silicide, and wherein the starting material of the structuration layer and the upper part of the substrate where the feet are engraved have a relationship between their rupture limits greater than or equal to 1. 
     
     
         5 . (canceled) 
     
     
         6 . The method according to  claim 1 , wherein the preparation of the structuration layer in stage a) is carried out by depositing or by growing said structuration layer on top of the substrate through a microelectronics technique selected from the group consisting of thermal growth, chemical vapor deposition, sputtering, and evaporation. 
     
     
         7 . The method according to  claim 1 , wherein the formation of the foot of each microparticle in stage c) is carried out by partially engraving the upper part of the substrate located beneath the microparticles using a microelectronic technique, with a variable cross-section of the foot having two different parts, where one part is narrower than the other, or with one constant cross-section of the foot that is less than the cross-section of the microparticle. 
     
     
         8 . The method according to  claim 7 , wherein the foot has a constant cross section that is less than or equal to 50% of the cross section of the microparticles. 
     
     
         9 . The method according to  claim 7 , wherein the partial engraving of the foot is carried out via a lateral physical etching or a lateral chemical etching. 
     
     
         10 . The method according to  claim 1 , wherein the microparticles are shaped in stage b) using photo-lithographic techniques. 
     
     
         11 . The method according to  claim 1 , wherein the microparticles are shaped all with the same shape and size or in two or more groups with different shapes and sizes. 
     
     
         12 . (canceled) 
     
     
         13 . The method according to  claim 1 , wherein the functionalization of stage d) is carried out using a molecule-printing technique selected from the group consisting of microcontact printing, dip-pen nanolithography, and polymer-pen lithography technique. 
     
     
         14 . The method according to  claim 1 , wherein the molecular component is a molecule with chemical and/or biological activity, selected from the group consisting of organic compounds, polymers, peptides, proteins, nucleotides, nucleic acids, and any combination thereof. 
     
     
         15 . The method according to  claim 1 , wherein the surface of each microparticle is functionalized in stage d) with more than one different molecular element, or with a single molecular element more than one time. 
     
     
         16 . The method according to  claim 1 , which further comprises:
 e) breaking the feet that support the microparticles by applying mechanical breaking loads in order to separate said microparticles from the substrate and individualize them.   
     
     
         17 . The method according to  claim 16 , wherein the controlled mechanical breaking load of the foot of each microparticle is applied by means of a technique selected from the group consisting of rasping, cutting, cryofracturing, and applying an adhesive material on the already functionalized surface of the microparticles and subsequently pulling it off, and dissolving the adhesive in media that do not affect the molecular functionalization of the microparticle. 
     
     
         18 . The method according to  claim 16 , which further comprises:
 f) gathering the individualized microparticles in a suspension medium.   
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . (canceled) 
     
     
         22 . A planar microparticle with surface molecular multiplexing individualized and released using the method defined in  claim 17 . 
     
     
         23 . A suspension of microparticles with surface molecular multiplexing obtained using the method defined in  claim 18 . 
     
     
         24 . (canceled) 
     
     
         25 . (canceled) 
     
     
         26 . (canceled) 
     
     
         27 . A method for detecting, analyzing and/or acting upon one or more parameters of a sample, the parameters being selected from the group consisting of chemical parameters, biological parameters and a simultaneous mixture thereof, the method comprising:
 adding to the sample one or more microparticles according to  claim 22 , and measuring a signal emitted by at least one of the microparticles.   
     
     
         28 . The method according to  claim 27 , further comprising transporting drugs or reagents incorporated into the microparticle. 
     
     
         29 . A method for detecting, analyzing and/or acting upon one or more parameters of a sample, the parameters being selected from the group consisting of chemical parameters, biological parameters and a simultaneous mixture thereof, the method comprising:
 adding to the sample a microparticle suspension according to  claim 23 , and measuring the signal emitted by at least one of the microparticles.