Reverse Electrochemical Sensing of FLT3-ITD Mutations in Acute Myeloid Leukemia Using Gold Sputtered ZnO-Nanorod Configured DNA Biosensors

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 diagnost...

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Main Authors: Ramesh Thevendran, Kai Loong Foo, Mohd Hazwan Hussin, Emmanuel Jairaj Moses, Marimuthu Citartan, Haarindraprasad Rajintra Prasad, Solayappan Maheswaran
Format: Article
Language:English
Published: MDPI AG 2022-03-01
Series:Biosensors
Subjects:
Online Access:https://www.mdpi.com/2079-6374/12/3/170
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author Ramesh Thevendran
Kai Loong Foo
Mohd Hazwan Hussin
Emmanuel Jairaj Moses
Marimuthu Citartan
Haarindraprasad Rajintra Prasad
Solayappan Maheswaran
author_facet Ramesh Thevendran
Kai Loong Foo
Mohd Hazwan Hussin
Emmanuel Jairaj Moses
Marimuthu Citartan
Haarindraprasad Rajintra Prasad
Solayappan Maheswaran
author_sort Ramesh Thevendran
collection DOAJ
description 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.
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spelling doaj.art-6c76a06286de49da94dbd62034306da02023-11-24T00:36:36ZengMDPI AGBiosensors2079-63742022-03-0112317010.3390/bios12030170Reverse Electrochemical Sensing of FLT3-ITD Mutations in Acute Myeloid Leukemia Using Gold Sputtered ZnO-Nanorod Configured DNA BiosensorsRamesh Thevendran0Kai Loong Foo1Mohd Hazwan Hussin2Emmanuel Jairaj Moses3Marimuthu Citartan4Haarindraprasad Rajintra Prasad5Solayappan Maheswaran6Infectomics Cluster, Advanced Medical & Dental Institute, Universiti Sains Malaysia, Bertam, Kepala Batas 13200, MalaysiaNano Biochip Research Group, Institute of Nano Electronic Engineering, Universiti Malaysia Perlis, Kangar 01000, MalaysiaMaterials Technology Research Group (MaTReC), School of Chemical Sciences, Universiti Sains Malaysia, Minden 11800, MalaysiaRegenerative Medicine Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, Kepala Batas 13200, MalaysiaInfectomics Cluster, Advanced Medical & Dental Institute, Universiti Sains Malaysia, Bertam, Kepala Batas 13200, MalaysiaFaculty of Engineering and Computer Technology, AIMST University, Semeling 08100, MalaysiaRegenerative Medicine Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, Kepala Batas 13200, MalaysiaDetection 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.https://www.mdpi.com/2079-6374/12/3/170acute myeloid leukemiaDNA biosensorFLT3-ITDAu sputtered-ZnO nanorodselectrochemical impedance spectroscopy
spellingShingle Ramesh Thevendran
Kai Loong Foo
Mohd Hazwan Hussin
Emmanuel Jairaj Moses
Marimuthu Citartan
Haarindraprasad Rajintra Prasad
Solayappan Maheswaran
Reverse Electrochemical Sensing of FLT3-ITD Mutations in Acute Myeloid Leukemia Using Gold Sputtered ZnO-Nanorod Configured DNA Biosensors
Biosensors
acute myeloid leukemia
DNA biosensor
FLT3-ITD
Au sputtered-ZnO nanorods
electrochemical impedance spectroscopy
title Reverse Electrochemical Sensing of FLT3-ITD Mutations in Acute Myeloid Leukemia Using Gold Sputtered ZnO-Nanorod Configured DNA Biosensors
title_full Reverse Electrochemical Sensing of FLT3-ITD Mutations in Acute Myeloid Leukemia Using Gold Sputtered ZnO-Nanorod Configured DNA Biosensors
title_fullStr Reverse Electrochemical Sensing of FLT3-ITD Mutations in Acute Myeloid Leukemia Using Gold Sputtered ZnO-Nanorod Configured DNA Biosensors
title_full_unstemmed Reverse Electrochemical Sensing of FLT3-ITD Mutations in Acute Myeloid Leukemia Using Gold Sputtered ZnO-Nanorod Configured DNA Biosensors
title_short Reverse Electrochemical Sensing of FLT3-ITD Mutations in Acute Myeloid Leukemia Using Gold Sputtered ZnO-Nanorod Configured DNA Biosensors
title_sort reverse electrochemical sensing of flt3 itd mutations in acute myeloid leukemia using gold sputtered zno nanorod configured dna biosensors
topic acute myeloid leukemia
DNA biosensor
FLT3-ITD
Au sputtered-ZnO nanorods
electrochemical impedance spectroscopy
url https://www.mdpi.com/2079-6374/12/3/170
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