Bioelectronic sensor technology for detection of cystic fibrosis and hereditary hemochromatosis mutations.
BACKGROUND
Bioelectronic sensors, which combine microchip and biological components, are an emerging technology in clinical diagnostic testing. An electronic detection platform using DNA biochip technology (eSensor) is under development for molecular diagnostic applications. Owing to the novelty of these devices, demonstrations of their successful use in practical diagnostic applications are limited.


OBJECTIVE
To assess the performance of the eSensor bioelectronic method in the validation of 6 Epstein-Barr virus-transformed blood lymphocyte cell lines with clinically important mutations for use as sources of genetic material for positive controls in clinical molecular genetic testing. Two cell lines carry mutations in the CFTR gene (cystic fibrosis), and 4 carry mutations in the HFE gene (hereditary hemochromatosis).


METHODS
Samples from each cell line were sent for genotype determination to 6 different molecular genetic testing facilities, including the laboratory developing the DNA biochips. In addition to the bioelectronic method, at least 3 different molecular diagnostic methods were used in the analysis of each cell line. Detailed data were collected from the DNA biochip output, and the genetic results were compared with those obtained using the more established methods.


RESULTS
We report the successful use of 2 applications of the bioelectronic platform, one for detection of CFTR mutations and the other for detection of HFE mutations. In all cases, the results obtained with the DNA biochip were in concordance with those reported for the other methods. Electronic signal output from the DNA biochips clearly differentiated between mutated and wild-type alleles. This is the first report of the use of the cystic fibrosis detection platform.


CONCLUSIONS
Bioelectronic sensors for the detection of disease-causing mutations performed well when used in a "real-life" situation, in this case, a validation study of positive control blood lymphocyte cell lines with mutations of public health importance. This study illustrates the practical potential of emerging bioelectronic DNA detection technologies for use in current molecular diagnostic applications.
Bernacki
Susan H
SH
Department of Pathology, Duke University Medical Center, Durham, NC, USA.
Farkas
Daniel H
DH
Shi
Wenmei
W
Chan
Vivian
V
Liu
Yenbou
Y
Beck
Jeanne C
JC
Bailey
Karen Snow
KS
Pratt
Victoria M
VM
Monaghan
Kristin G
KG
Matteson
Karla J
KJ
Schaefer
Frederick V
FV
Friez
Michael
M
Shrimpton
Antony E
AE
Stenzel
Timothy T
TT
D001483:Base Sequence; D015374:Biosensing Techniques / Q000379:methods*; D001709:Biotechnology / Q000379:methods; D002461:Cell Line, Transformed; D003550:Cystic Fibrosis / Q000175:diagnosis*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods*; D004581:Electronics; D005838:Genotype; D006432:Hemochromatosis / Q000175:diagnosis* / Q000235:genetics; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis
C505032:CFTR protein, human; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator