Rapid and label-free nanomechanical detection of biomarker transcripts in human RNA.
The availability of entire genome sequences has triggered the development of microarrays for clinical diagnostics that measure the expression levels of specific genes. Methods that involve labelling can achieve picomolar detection sensitivity, but they are costly, labour-intensive and time-consuming. Moreover, target amplification or biochemical labelling can influence the original signal. We have improved the biosensitivity of label-free cantilever-array sensors by orders of magnitude to detect mRNA biomarker candidates in total cellular RNA. Differential gene expression of the gene 1-8U, a potential marker for cancer progression or viral infections, has been observed in a complex background. The measurements provide results within minutes at the picomolar level without target amplification, and are sensitive to base mismatches. This qualifies the technology as a rapid method to validate biomarkers that reveal disease risk, disease progression or therapy response. We foresee cantilever arrays being used as a tool to evaluate treatment response efficacy for personalized medical diagnostics.
Zhang
J
J
NCCR Nanoscale Science, Institute of Physics, University of Basel, Klingelbergstrasse 82, CH-4056 Basel, Switzerland.
Lang
H P
HP
Huber
F
F
Bietsch
A
A
Grange
W
W
Certa
U
U
McKendry
R
R
Güntherodt
H-J
HJ
Hegner
M
M
Gerber
Ch
Ch
D015415:Biomarkers / Q000032:analysis; D004867:Equipment Design; D019544:Equipment Failure Analysis; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D019563:Mechanics; D036103:Nanotechnology / Q000295:instrumentation*; D020411:Oligonucleotide Array Sequence Analysis / Q000295:instrumentation*; D012313:RNA / Q000235:genetics*; D013194:Staining and Labeling; D014157:Transcription Factors / Q000235:genetics*; D014159:Transducers
D015415:Biomarkers; D005819:Genetic Markers; D014157:Transcription Factors; D012313:RNA