Patterning device

Abstract

A novel miniaturized and highly automated method for the controlled printing of large arrays of nano- to femtoliter droplets is presented by actively transporting mother droplets over hydrophilic-in-hydrophobic micropatches. The proposed technology consists of single plate or double-plate devices where mother droplets can be actuated and hydrophilic-in-hydrophobic micropatches on one or both plates of the device where nano- to femtoliter droplets are printed. Due to the selective wettability of the more wettable hydrophilic micropatches in a hydrophobic matrix, large nano- to femtoliter droplet arrays are created when mother droplets are transported over these arrays. The parent droplets can be moved by different droplet actuation principles, for example, by using the principle of electrowetting-on-dielectric droplet actuation. We propose another method that uses two plates that are placed on top of each other while being separated by a spacer. One plate is dedicated to confirming and guiding of parent droplets by using hydrophilic patches in a hydrophobic matrix, while the other plate contains hydrophilic-in-hydrophobic arrays dedicated to the printing of nano- to femtoliter droplets. When the plate dedicated to parent droplet guiding is rotated over the plate dedicated to printing of nano- to femtoliter droplets, nano- to femtoliter droplets are dispensed inside the hydrophilic-in-hydrophobic array due to their selective wettability. All these proposed methods allow the parent droplets to be moved over the hydrophilic-in-hydrophobic arrays many times, providing unique advantages for performing bio-assays or miniaturized materials synthesis in nano- to femtoliter sized droplets. Upon the controlled evaporation of the dispensed droplets of solution, large arrays of the printed material can be generated on an automated way in seconds of time on a very flexible way. The method disclosed herein provides a distinct nano- to femtoliter droplet printing technique for a wide variety of applications such as protein- or cell-based bio-assays or printing of crystalline structures, suspensions of nanoparticles or components for microelectronics.

1 . A method of printing a pattern or an array of nano- to femtoliter volume liquid droplets, characterized in that the method comprises moving or transporting a micro- or mililiter-sized parent droplet over a hydrophilic-in-hydrophobic pattern forming an array of hydrophilic elements in or onto a hydrophobic surface so that the parent droplet is divided into nano- to femtoliter droplets by releasing a divisional nano- to femtoliter droplet per hydrophilic element which the parent droplet touches so creating a printed nano- or femtoliter droplet array or pattern. 
     
     
         2 . The method according to  claim 1 , wherein the parent droplet is electrostatically transported with electrowetting-on-dielectric actuation over an array of conductive elements covered with a hydrophobic insulator. 
     
     
         3 . The method according to  claim 2 , wherein activation/deactivation of the conductive elements leads to transport of the parent droplet to the activated/deactivated conductive elements. 
     
     
         4 . The method according to  claim 1 , wherein the distance between the separate hydrophilic elements of the created array is minimally the length of one element of these features or wherein the distance between the hydrophilic elements is at least the length or diameter of one said hydrophilic element to prevent pinning of the mother droplet to the surface of the device. 
     
     
         5 . The method according to  claim 1 , further comprising moving or transporting parent droplets sandwiched between two, by a spacer separated, plates of which one of these plates contains hydrophilic guidance patches or wells in a hydrophobic matrix for guiding a parent droplet over an hydrophilic-in-hydrophobic pattern to capture or deposit nano- to femtoliter droplets from the parent droplet and wherein the one plate is mechanically or manually rotated over the other plate. 
     
     
         6 . The method according to  claim 1 , wherein the method is a high-throughput method of printing wherein several parent droplets are moved or transported in parallel over several regions containing hydrophilic-in-hydrophobic micropatterns. 
     
     
         7 . The method according to  claim 1 , wherein >1000 parent droplets are moved or transported over a pattern of hydrophilic-in-hydrophobic micropatterns in different sequences printing components or solutions from the parent droplets inside the hydrophilic elements of the array. 
     
     
         8 . The method according to  claim 1 , wherein a larger parent droplet is transported over a hydrophilic-in-hydrophobic micropattern by means of electrowetting-on-dielectric based droplet actuation. 
     
     
         9 . The method according to  claim 1 , wherein suspended particles or elements from a divisional droplet released from the parent droplet are printed inside the hydrophilic elements of the hydrophilic-in-hydrophobic pattern. 
     
     
         10 . The method according to  claim 9 , wherein suspended particles or elements are captured and bound inside the hydrophilic elements of the hydrophilic-in-hydrophobic array and wherein the parent droplet that contains the suspended particles or elements is moved or transported over the hydrophilic-in-hydrophobic pattern at least 1 time to fill all hydrophilic elements with one or multiple particles from the parent droplet. 
     
     
         11 . The method according to  claim 9 , wherein the hydrophilic element comprises a microwell, i.e. a well with diameter or length and depth of 1 μm-1000 μm, or a micropatch with a depth of maximal 1 μm and a maximal length or diameter of 1000 μm. 
     
     
         12 . The method according to  claim 1 , wherein the suspended particles in the parent droplet are micro- or nanoparticles with a diameter of 1 nm to 1000 μm that are deposited inside the hydrophilic elements. 
     
     
         13 . The method according to  claim 1 , wherein the suspended micro- and nanoparticles are magnetic and their movement towards and inside of the hydrophilic elements is facilitated by placing a magnet underneath the hydrophilic elements and thereby accelerates trapping of magnetic particles in the hydrophilic elements and facilitating trapping of the magnetic particles in the hydrophilic elements. 
     
     
         14 . The method according to  claim 1 , wherein all movement of parent droplets of deposition of nano- to femtoliter droplets is executed in an oil instead of an air environment such that the evaporation of parent droplets and the deposited nano- to femtoliter droplets is prevented. 
     
     
         15 . The method according to  claim 1 , wherein the hydrophilic element is a microwell, a slide, a chip or a membrane. 
     
     
         16 . The method according to  claim 1 , wherein the fluid comprises biomolecules or other materials for the printing of solid-state materials. 
     
     
         17 . The method according to  claim 1 , wherein the larger parent droplet has a microliter volume. 
     
     
         18 . The method according to  claim 1 , wherein the larger parent droplet is divided into smaller nanoliter divisional droplets. 
     
     
         19 . The method according to  claim 1 , wherein the larger parent droplet is divided into smaller pico- or femtoliter divisional droplets. 
     
     
         20 . The method according to  claim 1 , wherein the liquid is an aqueous solution. 
     
     
         21 . The method according to  claim 1 , wherein the liquid is an organic solvent. 
     
     
         22 . The method according to  claim 1 , wherein the liquid is a solution comprising organic and inorganic building blocks. 
     
     
         23 . The method according to  claim 1 , wherein the liquid is a suspension of micro- or nanoparticles and biological samples. 
     
     
         24 . The method according to  claim 1 , wherein the shape and size of the printed divisional droplet is defined by the shape and size of the hydrophilic element. 
     
     
         25 . The method according to  claim 24 , wherein the hydrophilic element is a microwell. 
     
     
         26 . The method according to  claim 9 , wherein the loading efficiency of single or multiple particles are maximized to 98% or more by moving a droplet of particle suspension multiple times over the array until all hydrophilic elements comprise particles or until all microwells are filled with particles. 
     
     
         27 . The method according to  claim 7 , wherein droplets of particle suspensions are transported over the array of hydrophilic-in-hydrophobic microwells in an oil matrix, thereby preventing evaporation of the printed femtoliter droplets and the liquid surrounding the beads when being patterned in the microwells. 
     
     
         28 . The method according to  claim 1 , wherein a parent droplet comprising a solute is divided into divisional nano- to femtoliter droplets and whereby the nano- to femtoliter droplet solutes are crystallized to their respective hydrophilic-in-hydrophobic elements and results in deposited single or multiple crystals originating from the solution in the parent droplet. 
     
     
         29 . The method according to  claim 14 , wherein a bio-assay is performed in the printed nano- to femtoliter droplets in which fluorophores are generated in the bio-assay and confined to the nano- to femtoliter droplets when the droplet printing was performed in oil and wherein the generated fluorescent signal is detectable with fluorescence microscopy. 
     
     
         30 . The method according to  claim 28 , wherein this is so as to perform an enzyme-linked immunosorbent assay or polymerase chain reaction inside the printed nano- to femtoliter droplets. 
     
     
         31 . The method according to  claim 29 , wherein the bio-assays are performed on a printed particle from a parent droplet suspension or a parent droplet solute.