Fully integrated miniaturized planar liquid sample handling and analysis device

Abstract

A miniaturized total analysis system ("μ-TAS") comprising a miniaturized planar column device is described for use in liquid phase analysis. The μ-TAS comprises microstructures fabricated by laser ablation in a variety of novel support substrates. The μ-TAS includes associated laser-ablated features required for integrated sample analysis, such as analyte detection means and fluid communication means. μ-TAS constructed according to the invention is useful in any analysis system for detecting and analyzing small and/or macromolecular solutes in the liquid phase and may employ chromatographic separation means, electrophoretic separation means, electrochromatographic separation means, or combinations thereof.

We claim: 
     
       1. A miniaturized total analysis system (μ-TAS) comprising a miniaturized column device comprising: (a) a substrate having first and second substantially planar opposing surfaces wherein said substrate is comprised of a material other than silicon or silicon dioxide, said substrate having a first microchannel laser-ablated in the first planar surface, wherein said first microchannel comprises more than one sample handling region;   (b) a cover plate arranged over the first planar surface, said cover plate in combination with the first microchannel forming a first sample processing compartment, wherein the sample handling regions define a sample flow component in fluid communication with a sample treatment component; and   (c) at least one inlet port and at least one outlet port communicating with the first sample processing compartment, said inlet and outlet ports enabling the passage of fluid from an external source through the sample processing compartment.   
     
     
       2. The μ-TAS of claim 1, wherein said first sample processing compartment comprises a serial arrangement of sample handling regions which define a serial arrangement of alternating sample flow components and sample treatment components. 
     
     
       3. The μ-TAS of claim 2, further comprising detection means laser ablated in the substrate, wherein said detection means is in communication with the first sample processing compartment thereby enabling the detection of a sample passing through the sample processing compartment. 
     
     
       4. The μ-TAS of claim 3, further comprising detection means laser ablated in the substrate, wherein said detection means is in communication with the sample flow component thereby enabling the detection of a sample passing through the sample processing compartment. 
     
     
       5. The μ-TAS of claim 3, further comprising access ports in fluid communication of the sample flow component, thereby enabling the passage of fluid between an external source and the sample flow component. 
     
     
       6. The μ-TAS of claim 2, further comprising access ports in fluid communication with the sample flow component, thereby enabling the passage of fluid between an external source and the sample flow component. 
     
     
       7. The μ-TAS of claim 2, further comprising: (a) a reservoir microstructure laser-ablated in the first planar surface, wherein the cover plate in combination with said microstructure define a reservoir compartment having an inlet means and an outlet means;   (b) a conducting microchannel laser-ablated in the first planar surface, wherein the cover plate in combination with said conducting microchannel defines a sample flow component having first and second ends respectively in fluid communication with the sample processing compartment and the reservoir compartment outlet means;   (c) an orifice in divertable fluid communication with the reservoir compartment inlet means, said orifice enabling the passage of fluid from an external source into the reservoir compartment; and   (d) a motive means enabling the displacement of a fluid from the reservoir compartment through the sample flow component and into the first sample processing compartment.   
     
     
       8. The μ-TAS of claim 7, further comprising: (a) a sample delivery means in fluid communication with the first sample processing compartment outlet port, said sample delivery means comprising a mixing chamber in fluid communication and in axial alignment with a fluid communication means and an outlet nozzle;   (b) a fluid source in divertable fluid communication with the fluid communication means; and   (c) a post-column collection device comprising a sample receiving means positioned relative to the outlet nozzle to receive eluent from the nozzle means.   
     
     
       9. The μ-TAS of claim 2, further comprising: (a) a sample delivery means in fluid communication with the first sample processing compartment outlet port, said sample delivery means comprising a mixing chamber in fluid communication and in axial alignment with a fluid communication means and an outlet nozzle;   (b) a fluid source in divertable fluid communication with the fluid communication means; and   (c) a post-column collection device comprising a sample receiving means positioned relative to the outlet nozzle to receive eluent from the nozzle means.   
     
     
       10. The μ-TAS of claim 2, further comprising: (a) a second microchannel having an inlet port and an outlet port laser ablated in the second planar surface;   (b) a second cover plate disposed over the second planar surface, said cover plate in combination with the second microchannel defining a second sample processing compartment;   (c) conduit means for communicating the outlet port of the first sample processing compartment and the inlet port of the second sample processing compartment with each other thereby forming a single continuous sample processing compartment, said conduit means comprising a laser-ablated aperture in the substrate, said aperture having an axis which is orthogonal to the planar surfaces.   
     
     
       11. The μ-TAS of claim 10, further comprising detection means comprising apertures laser-ablated respectively in the first and second cover plates and arranged in co-axial communication with the conduit means. 
     
     
       12. The μ-TAS of claim 11, further comprising access ports in fluid communication of the sample flow component, thereby enabling the passage of fluid between an external source and the sample flow component. 
     
     
       13. The μ-TAS of claim 10, further comprising access ports in fluid communication with the sample flow component, thereby enabling the passage of fluid between an external source and the sample flow component. 
     
     
       14. The μ-TAS of claim 10, further comprising: (a) a reservoir microstructure laser-ablated in the first planar surface, wherein the cover plate in combination with said microstructure define a reservoir compartment having an inlet means and an outlet means;   (b) a conducting microchannel laser-ablated in the first planar surface, wherein the cover plate in combination with said conducting microchannel defines a sample flow component having first and second ends respectively in fluid communication with the sample processing compartment and the reservoir compartment outlet means;   (c) an orifice in divertable fluid communication with the reservoir compartment inlet means, said orifice enabling the passage of fluid from an external source into the reservoir compartment; and   (d) a motive means enabling the displacement of a fluid from the reservoir compartment through the sample flow component and into the first sample processing compartment.   
     
     
       15. The μ-TAS of claim 14, further comprising: (a) a sample delivery means in fluid communication with the first sample processing compartment outlet port, said sample delivery means comprising a mixing chamber in fluid communication and in axial alignment with a fluid communication means and an outlet nozzle;   (b) a fluid source in divertable fluid communication with the fluid communication means; and   (c) a post-column collection device comprising a sample receiving means positioned relative to the outlet nozzle to receive eluent from the nozzle means.   
     
     
       16. The μ-TAS of claim 10, further comprising: (a) a sample delivery means in fluid communication with the first sample processing compartment outlet port, said sample delivery means comprising a mixing chamber in fluid communication and in axial alignment with a fluid communication means and an outlet nozzle;   (b) a fluid source in divertable fluid communication with the fluid communication means; and   (c) a post-column collection device comprising a sample receiving means positioned relative to the outlet nozzle to receive eluent from the nozzle means.   
     
     
       17. A μ-TAS device comprising: (a) a support body formed from a substrate comprised of a material other than silicon or silicon dioxide, said support body having first and second component halves each having substantially planar interior surfaces;   (b) a first microchannel laser-ablated in the interior surface of the first support body half and a second microchannel laser-ablated in the interior surface of the second support body half, wherein said first and second microchannels are arranged so as to provide the mirror image of the other;   (c) a sample processing compartment formed by aligning the interior surfaces of the support body halves in facing abutment with each other whereby the microchannels define said sample processing compartment and wherein said sample processing compartment comprises sample handling regions which define a sample flow component in fluid communication with a sample treatment component; and   (d) at least one inlet port and at least one outlet port communicating with the sample processing compartment, said ports enabling the passage of fluid from an external source through the sample processing compartment.   
     
     
       18. The μ-TAS of claim 17, wherein said sample processing compartment comprises a serial arrangement of sample handling regions which define a serial arrangement of alternating sample flow components and sample treatment components. 
     
     
       19. The μ-TAS of claim 18, further comprising detection means laser ablated in the substrate, wherein said detection means is in communication with the sample processing compartment thereby enabling the detection of a sample passing through the sample processing compartment. 
     
     
       20. The μ-TAS of claim 19, further comprising detection means laser ablated in the substrate, wherein said detection means is in communication with the sample flow component thereby enabling the detection of a sample passing through the sample processing compartment. 
     
     
       21. The μ-TAS of claim 19, further comprising access ports in fluid communication of the sample flow component, thereby enabling the passage of fluid between an external source and the sample flow component. 
     
     
       22. The μ-TAS of claim 18, further comprising access ports in fluid communication with the sample flow component, thereby enabling the passage of fluid between an external source and the sample flow component. 
     
     
       23. The μ-TAS of claim 18, further comprising: (a) a reservoir microstructure laser-ablated in the first planar surface, wherein the cover plate in combination with said microstructure define a reservoir compartment having an inlet means and an outlet means;   (b) a conducting microchannel laser-ablated in the first planar surface, wherein the cover plate in combination with said conducting microchannel defines a sample flow component having first and second ends respectively in fluid communication with the sample processing compartment and the reservoir compartment outlet means;   (c) an orifice in divertable fluid communication with the reservoir compartment inlet means, said orifice enabling the passage of fluid from an external source into the reservoir compartment; and   (d) a motive means enabling the displacement of a fluid from the reservoir compartment through the sample flow component and into the sample processing compartment.   
     
     
       24. The μ-TAS of claim 23, further comprising: (a) a sample delivery means in fluid communication with the sample processing compartment outlet port, said sample delivery means comprising a mixing chamber in fluid communication and in axial alignment with a fluid communication means and an outlet nozzle;   (b) a fluid source in divertable fluid communication with the fluid communication means; and   (c) a post-column collection device comprising a sample receiving means positioned relative to the outlet nozzle to receive eluent from the nozzle means.   
     
     
       25. The μ-TAS of claim 18, further comprising: (a) a sample delivery means in fluid communication with the first sample processing compartment outlet port, said sample delivery means comprising a mixing chamber in fluid communication and in axial alignment with a fluid communication means and an outlet nozzle;   (b) a fluid source in divertable fluid communication with the fluid communication means; and   (c) a post-column collection device comprising a sample receiving means positioned relative to the outlet nozzle to receive eluent from the nozzle means. .Iadd.   
     
     
       26.  The μ-TAS device of claim 17, wherein the support body further comprises a fold means separating said first and second component halves..Iaddend..Iadd.27. The μ-TAS device of claim 18, wherein the support body further comprises a fold means separating said first and second component halves..Iaddend..Iadd.28. The μ-TAS device of claim 23, wherein the support body further comprises a fold means separating said first and second component halves..Iaddend..Iadd.29. The μ-TAS device of claim 25, wherein the support body further comprises a fold means separating said first and second component halves..Iaddend..Iadd.30. The μ-TAS device of claim 26, wherein said first and second component halves further comprise micro-alignment means..Iaddend..Iadd.31. The μ-TAS device of claim 27, wherein said first and second component halves further comprise micro-alignment means..Iaddend..Iadd.32. The μ-TAS device of claim 28, wherein said first and second component halves further comprise micro-alignment means..Iaddend..Iadd.33. The μ-TAS device of claim 29, wherein said first and second component halves further comprise micro-alignment means..Iaddend..Iadd.34. The μ-TAS device of claim 30, wherein said micro-alignment means comprises a plurality of holes laser-ablated in said component halves, wherein the holes are arranged such that alignment of corresponding holes in said first and second component halves enables the precise alignment of said first and second microchannels to form said sample processing compartment..Iaddend..Iadd.35. The μ-TAS device of claim 31, wherein said micro-alignment means comprises a plurality of holes laser-ablated in said component halves, wherein the holes are arranged such that alignment of corresponding holes in said first and second component halves enables the precise alignment of said first and second microchannels to form said sample processing compartment..Iaddend..Iadd.36. The μ-TAS device of claim 32, wherein said micro-alignment means comprises a plurality of holes laser-ablated in said component halves, wherein the holes are arranged such that alignment of corresponding holes in said first and second component halves enables the precise alignment of said first and second microchannels to form said sample processing compartment..Iaddend..Iadd.37. The μ-TAS device of claim 33, wherein said micro-alignment means comprises a plurality of holes laser-ablated in said component halves, wherein the holes are arranged such that alignment of corresponding holes in said first and second component halves enables the precise alignment of said first and second microchannels to form said sample processing compartment..Iaddend..Iadd.38. The μ-TAS device of claim 30, wherein said micro-alignment means comprises corresponding structures formed in said component halves, said structures comprising a plurality of depressions arranged on one of said component halves and a plurality of projections arranged on the other of said component halves, said projections configured to mate with said depressions such that alignment of the corresponding structures enables the precise alignment of said first and second microchannels to form said sample processing 
     
     
        compartment..Iaddend..Iadd.39.  The μ-TAS device of claim 31, wherein said micro-alignment means comprises corresponding structures formed in said component halves, said structures comprising a plurality of depressions arranged on one of said component halves and a plurality of projections arranged on the other of said component halves, said projections configured to mate with said depressions such that alignment of the corresponding structures enables the precise alignment of said first and second microchannels to form said sample processing compartment..Iaddend..Iadd.40. The μ-TAS device of claim 32, wherein said micro-alignment means comprises corresponding structures formed in said component halves, said structures comprising a plurality of depressions arranged on one of said component halves and a plurality of projections arranged on the other of said component halves, said projections configured to mate with said depressions such that alignment of the corresponding structures enables the precise alignment of said first and second microchannels to form said sample processing compartment..Iaddend..Iadd.41. The μ-TAS device of claim 33, wherein said micro-alignment means comprises corresponding structures formed in said component halves, said structures comprising a plurality of depressions arranged on one of said component halves and a plurality of projections arranged on the other of said component halves, said projections configured to mate with said depressions such that alignment of the corresponding structures enables the precise alignment of said first and second microchannels to form said sample processing compartment..Iaddend..Iadd.42. The μ-TAS device comprising: (a) a substrate formed from a substrate comprised of a material other than silicon or silicon dioxide, said substrate having a column portion and first and second cover plate portions, said column portion having first and second substantially planar opposing surfaces,   said first and second cover plate portions each having at least one substantially planar surface,   said first cover plate portion separated from said column portion by at least one fold means such that said planar surface of said first cover plate portion can be folded to overlie said first planar surface of said column portion,   said second cover plate portion separated from said column portion by at least one fold means such that said planar surface of said second cover plate portion can be folded to overlie said second planar surface of said column portion;     (b) a first microchannel laser-ablated in said first surface of said column portion and a second microchannel laser-ablated in said second surface of said column portion;   (c) a conduit means laser ablated through said column portion communicating with a distal portion of said first microchannel and a first portion of said second microchannel;   (d) a separation compartment formed by aligning said planar surface of said first cover plate portion with said first surface of said column portion by folding said first fold means, and by further aligning said planar surface of said second cover plate portion with said second surface of said column portion by folding said second fold means; and   (e) a first aperture laser ablated in said first cover plate portion allowing fluid communication with said first microchannel and a second aperture laser ablated in said second cover plate portion allowing fluid communication with said second microchannel..Iaddend.