Apparatus for assay, synthesis and storage, and methods of manufacture, use, and manipulation thereof
The invention features methods of making devices, or “platens”, having a high-density array of through-holes, as well as methods of cleaning and refurbishing the surfaces of the platens. The invention further features methods of making high-density arrays of chemical, biochemical, and biological compounds, having many advantages over conventional, lower-density arrays. The invention includes methods by which many physical, chemical or biological transformations can be implemented in serial or in parallel within each addressable through-hole of the devices. Additionally, the invention includes methods of analyzing the contents of the array, including assaying of physical properties of the samples.
1. A method of creating a chemical array, the method comprising:
a) providing a platen having a plurality of through-holes and two opposing surfaces;
b) applying a mask to one or both surfaces of the platen to block at least some of the through-holes, while leaving other through-holes open;
c) exposing a surface of the platen to a reagent so that the reagent enters at least one of the open through-holes; and
d) repeating steps b) and c) with at least one different mask and at least one different reagent to create a chemical array;
loading at least some of the through-holes with a liquid sample comprising a biological compound;
performing a polymerase chain reaction on at least some of the biological compounds.
2. The method of claim 1 , wherein the mask is made of a polymer, an elastomer, paper, glass, or a semiconductor material.
3. The method of claim 1 , wherein the mask comprises mechanical valves, pin arrays, or gas jets.
4. The method of claim 1 , wherein the applying step forms a hermetic seal between the mask and the platen.
5. The method of claim 1 , wherein the reagent is a liquid, a gas, a solid, a powder, a gel, a solution, a suspension, a cell culture, a virus preparation, or electromagnetic radiation.
6. The method of claim 1 , wherein the mask is translated to expose different through-holes.
7. The method of claim 1 , wherein the mask has co-registration pins and holes such that alignment of pins and holes in the mask register with the throughholes in the platen.
8. The method of claim 1 , wherein multiple masks are part of a flexible tape, and the multiple masks are registered with the through-holes of the platen by advancing the tape.
9. A device for filling an array of wells in a platen, the device comprising:
a platen comprising an array of wells, the plurality of wells configured to receive a reagent each;
a holder adapted to accept the platen;
a nozzle comprising an aperture configured to inject a sample comprising a biological compound into at least some of wells; and
a valve that controls a flow of a sample through the nozzle, wherein the holder and nozzle can move with respect to each other.
10. The device of claim 9 , wherein at least some of the wells are characterized by a diameter of 10-300 micrometers.