Methods of fabrication of cartridges for biological analysis
Methods to fabricate reaction cartridges for biological sample preparation and analysis are disclosed. A cartridge may have a reaction chamber and openings to allow fluids to enter the chamber. The cartridge may also have handles to facilitate its use. Such cartridges may be used for polymerase chain reaction.
1. A method to fabricate a reaction cartridge, the method comprising
fabricating a top transparent layer, the top transparent layer having at least one handle, a top surface and a bottom surface, and wherein the top transparent layer comprises a prism structure and at least one opening;
fabricating a central layer on the bottom surface of the top transparent layer, the central layer comprising an enclosed space accessible to the at least one opening and having a bottom surface;
providing a metal back plate, the metal back plate having a top surface and a bottom surface, the bottom surface having a perimeter portion substantially distinct from a central portion;
depositing an adhesive layer on the perimeter portion of the top surface of the metal back plate;
aligning the adhesive layer to the bottom surface of the central layer;
pressing together the metal back plate, the top transparent layer and the central layer; and
irradiating the adhesive layer through the top transparent layer and the central layer, thereby curing the adhesive layer.
2. The method of claim 1 , further comprising:
depositing reagents on a central portion of the top surface of the metal back plate before the aligning the adhesive layer, thereby obtaining a reagent area;
aligning a mask layer over the top transparent layer, the mask layer having an area substantially corresponding to the reagent area in shape and size, thereby allowing irradiation of the adhesive layer but not allowing irradiation of the reagent area; and
irradiating the adhesive layer through the top transparent layer and the central layer, thereby curing the adhesive layer.
3. The method of claim 1 , wherein the fabricating the top transparent or central layer comprises injection molding, compression molding, 3D printing, embossing, nanostamping or rapid prototyping.
4. The method of claim 1 , wherein the central layer is fabricated by etching or molding the top transparent layer, thereby obtaining an enclosed space in the top transparent layer.
5. The method of claim 1 , wherein the central layer is fabricated by etching or cutting the metal back plate, thereby obtaining an enclosed space in the metal back plate.
6. The method of claim 1 , further comprising:
depositing reagents on a central portion of the bottom surface the top transparent layer before the aligning the adhesive layer, thereby obtaining a reagent area;
aligning a mask layer over the top transparent layer, the mask layer area substantially corresponding to the reagent area in shape and size, thereby allowing irradiation of the adhesive layer but not allowing irradiation of the reagent area; and
irradiating the adhesive layer through the top transparent layer and the central layer, thereby curing the adhesive.
7. The method of claim 2 , wherein the reagents are lyophilized or freeze dried.
8. The method of claim 6 , wherein the reagents are lyophilized or freeze dried.
9. The method of claim 1 , wherein the depositing an adhesive layer comprises depositing regularly spaced dots of adhesive by a robotic nozzle dispenser, and wherein the pressing together further comprises regulating pressure through a robot.
10. The method of claim 1 , wherein the depositing the adhesive layer comprises depositing a uniform line of adhesive by a robotic nozzle dispenser, and wherein the pressing together further comprises regulating pressure through a robot.
11. The method of claim 1 , wherein the depositing the adhesive layer comprises stamping a uniform line of adhesive by a robot dispenser, and wherein the pressing together further comprises regulating pressure through a robot.
12. The method of claim 1 , wherein the metal back plate is made of aluminum.
13. The method of claim 1 , wherein the top transparent layer is made of a material selected from the group consisting of cyclic olefin copolymer, cyclic olefin polymer, thermoplastic materials, metal, glass and elastomers.
14. The method of claim 1 , further comprising attaching a capillary to the at least one opening.
15. The method of claim 1 , further comprising attaching a pipette plug to the at least one opening.