IC-processed polymer nano-liquid chromatography system on-a-chip and method of making it

Abstract

Embodiments in accordance with the present invention relate to packed-column nano-liquid chromatography (nano-LC) systems integrated on-chip, and methods for producing and using same. The microfabricated chip includes a column, frits / filters, an injector, and a detector, fabricated in a process compatible with those conventionally utilized to form integrated circuits. The column can be packed with supports for various different stationary phases to allow performance of different forms of nano-LC, including but not limited to reversed-phase, normal-phase, adsorption, size-exclusion, affinity, and ion chromatography. A cross-channel injector injects a nanolitre / picolitre-volume sample plug at the column inlet. An electrochemical / conductivity sensor integrated at the column outlet measures separation signals. A self-aligned channel-strengthening technique increases pressure rating of the microfluidic system, allowing it to withstand the high pressure normally used in high performance liquid chromatography (HPLC). On-chip sample injection, separation, and detection of mixture of anions in water is successfully demonstrated using ion-exchange nano-LC.

Description

BACKGROUND OF THE INVENTION Separation of chemicals is widely and routinely performed in lots of industries and research labs. Liquid Chromatography (LC), and especially High Performance Liquid Chromatography (HPLC), is one of the most powerful and versatile separation techniques. Although LC column is normally made of capillary tubes due to fluidics limitations, the miniaturization of the column can actually improve separation performance. As shown in FIG. 15 where same separation chemistry applies, separated peak width is independent of column ID, while peak heights are larger for smaller columns and / or smaller beads. Conventional LC systems are also typically expensive and bulky. The separation columns, being of utmost importance in LC system, are also expensive and need replacements after a certain times of usage (typically about 100 times). Sample and solvent consumption cost is also very high. A miniaturized LC system could be cheaper, faster, and exhibit minimized sample ...

AI Technical Summary

Benefits of technology

Design and embodiments in accordance with the present invention relate to packed-column nano-liquid chromatography (nano-LC) systems integrated on-chip, and methods for producing and using same. The microfabricated chip includes a column, frits / filters, an injector, and a detector, fabricated in a process compatible with those conventionally utilized to form integrated circuits. The column can be packed with supports for various different stationary phases to allow performance of different forms of LC, including but not limited to reversed-phase, normal-phase, adsorption, size-exclusion, affinity, and ion chromatography. A cross-channel injector injects a nanolitre / picolitre-volume sample plug at the column inlet. An electrochemical / conductivity sensor integrated at the column outlet measures separation signals. A self-aligned channel-strengthening technique increases pressure rating of the microfluidic system, allowing it to withstand the high pressure normally used in nano-high performance liquid chromatography (nano-HPLC). On-chip sample injection, separation, and detection of mixture of anions in water is successfully demonstrated using ion-exchange nano-LC.

Problems solved by technology

Conventional LC systems are also typically expensive and bulky.

The separation columns, being of utmost importance in LC system, are also expensive and need replacements after a certain times of usage (typically about 100 times).

Sample and solvent consumption cost is also very high.

The need / market for miniaturized LC system is huge.

However, comparing to the intense interests in miniaturized electrophoresis system on-a-chip, little is published about miniaturizing LC system onto a single chip.

The main obstacles to miniaturization of LC systems are the lack of (1) a process to integrate various components of an LC system onto a monolithic chip; (2) high-pressure microfluidics needed for pumping liquid through densely-packed beads column; and (3) an approach to easily and reliably pack and seal chromatography supports (micro-beads) into the on-chip column.

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