FISH and chips: chromosomal analysis on microfluidic platforms

Abstract

Interphase fluorescence in situ hybridisation (FISH) is a sensitive diagnostic tool used for the detection of alterations in the genome on cell-by-cell basis. However, the cost-per-test and the technical complexity of current FISH protocols have slowed its widespread utilisation in clinical settings. For many cancers, the lack of a cost-effective and informative diagnostic method has compromised the quality of life for patients. We present the first demonstration of a microchip-based FISH protocol, coupled with a novel method to immobilise peripheral blood mononuclear cells inside microfluidic channels. These first on-chip implementations of FISH allow several chromosomal abnormalities associated with multiple myeloma to be detected with a ten-fold higher throughput and 1/10-th the reagent consumption of the traditional slide-based method. Moreover, the chip test is performed within hours whereas the conventional protocol required days. In addition, two on-chip methods to enhance the hybridisation aspects of FISH have been examined: mechanical and electrokinetic pumping. Similar agitation methods have led to significant improvements in hybridisation efficiency with DNA microarray work, but with this cell-based method the benefits were moderate. On-chip FISH technology holds promise for sophisticated and cost-effective screening of cancer patients at every clinic visit.