Reverse Electrochemical Sensing of FLT3-ITD Mutations in Acute Myeloid Leukemia Using Gold Sputtered ZnO-Nanorod Configured DNA Biosensors.
Ramesh ThevendranKai Loong FooMohd Hazwan HussinEmmanuel Jairaj MosesMarimuthu CitartanHaarindraprasad Rajintra PrasadSolayappan MaheswaranPublished in: Biosensors (2022)
Detection of genetic mutations leading to hematological malignancies is a key factor in the early diagnosis of acute myeloid leukemia (AML). FLT3-ITD mutations are an alarming gene defect found commonly in AML patients associated with high cases of leukemia and low survival rates. Available diagnostic assessments for FLT3-ITD are incapable of combining cost-effective detection platforms with high analytical performances. To circumvent this, we developed an efficient DNA biosensor for the recognition of AML caused by FLT3-ITD mutation utilizing electrochemical impedance characterization. The system was designed by adhering gold-sputtered zinc oxide (ZnO) nanorods onto interdigitated electrode (IDE) sensor chips. The sensing surface was biointerfaced with capture probes designed to hybridize with unmutated FLT3 sequences instead of the mutated FLT3-ITD gene, establishing a reverse manner of target detection. The developed biosensor demonstrated specific detection of mutated FLT3 genes, with high levels of sensitivity in response to analyte concentrations as low as 1 nM. The sensor also exhibited a stable functional life span of more than five weeks with good reproducibility and high discriminatory properties against FLT3 gene targets. Hence, the developed sensor is a promising tool for rapid and low-cost diagnostic applications relevant to the clinical prognosis of AML stemming from FLT3-ITD mutations.
Keyphrases
- acute myeloid leukemia
- label free
- allogeneic hematopoietic stem cell transplantation
- loop mediated isothermal amplification
- genome wide
- gold nanoparticles
- quantum dots
- copy number
- low cost
- single molecule
- real time pcr
- sensitive detection
- computed tomography
- end stage renal disease
- magnetic resonance imaging
- cell free
- gene expression
- room temperature
- circulating tumor
- ejection fraction
- magnetic resonance
- reduced graphene oxide
- mass spectrometry
- patient reported outcomes
- ionic liquid
- bone marrow
- dna methylation
- small molecule
- transcription factor
- tandem mass spectrometry
- liquid chromatography
- living cells
- circulating tumor cells