FISH and chips: chromosomal analysis on microfluidic platforms.
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.
Sieben
V J
VJ
University of Alberta, Department of Electrical and Computer Engineering, CanadaCross Cancer Institute, Edmonton, Canada.
Debes Marun
C S
CS
Pilarski
P M
PM
Kaigala
G V
GV
Pilarski
L M
LM
Backhouse
C J
CJ
D020732:Cytogenetic Analysis / Q000295:instrumentation* / Q000379:methods; D004273:DNA, Neoplasm / Q000235:genetics*; D004867:Equipment Design; D019544:Equipment Failure Analysis; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000295:instrumentation* / Q000379:methods; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation* / Q000379:methods; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000235:genetics*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm