title: Biodosimetry on small blood volume using gene expression assay.
abstract: This paper reports the development of a biodosimetry device suitable for rapidly measuring expression levels of a low-density gene set that can define radiation exposure, dose and injury in a public health emergency. The platform comprises a set of 14 genes selected on the basis of their abundance and differential expression level in response to radiation from an expression profiling series measuring 41,000 transcripts. Gene expression is analyzed through direct signal amplification using a quantitative Nuclease Protection Assay (qNPA). This assay can be configured as either a high-throughput microplate assay or as a handheld detection device for individual point-of-care assays. Recently, we were able to successfully develop the qNPA platform to measure gene expression levels directly from human whole blood samples. The assay can be performed with volumes as small as 30 microL of whole blood, which is compatible with collection from a fingerstick. We analyzed in vitro irradiated blood samples with qNPA. The results revealed statistically significant discrimination between irradiated and non-irradiated samples. These results indicate that the qNPA platform combined with a gene profile based on a small number of genes is a valid test to measure biological radiation exposure. The scalability characteristics of the assay make it appropriate for population triage. This biodosimetry platform could also be used for personalized monitoring of radiotherapy treatments received by patients.
authors.affiliation: Applied NanoBioscience Center and Medicine, University of Arizona, Phoenix, AZ 85004-2157, USA. mbrengues@email.arizona.edu
authors.forename: Muriel
authors.initials: M
authors.lastname: Brengues
authors.forename: Brigitte
authors.initials: B
authors.lastname: Paap
authors.forename: Michael
authors.initials: M
authors.lastname: Bittner
authors.forename: Sally
authors.initials: S
authors.lastname: Amundson
authors.forename: Bruce
authors.initials: B
authors.lastname: Seligmann
authors.forename: Ronald
authors.initials: R
authors.lastname: Korn
authors.forename: Ralf
authors.initials: R
authors.lastname: Lenigk
authors.forename: Frederic
authors.initials: F
authors.lastname: Zenhausern
mesh_terms: D001681:Biological Assay / Q000295:instrumentation* / Q000379:methods; D015415:Biomarkers / Q000097:blood; D001774:Blood Chemical Analysis / Q000295:instrumentation* / Q000379:methods; D001798:Blood Proteins / Q000032:analysis*; D004867:Equipment Design; D019544:Equipment Failure Analysis; D020869:Gene Expression Profiling / Q000295:instrumentation* / Q000379:methods; D006801:Humans; D008832:Microchemistry / Q000295:instrumentation / Q000379:methods; D040081:Protein Array Analysis / Q000295:instrumentation*; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000097:blood* / Q000175:diagnosis*; D011874:Radiometry / Q000295:instrumentation*
chemical_list: D015415:Biomarkers; D001798:Blood Proteins