Highly Sensitive and Quick Detection of Acute Myocardial Infarction Biomarkers Using In₂O₃ Nanoribbon Biosensors Fabricated Using Shadow Masks

Abstract

We demonstrate a scalable and facile lithography-free method for fabricating highly uniform and sensitive InO nanoribbon biosensor arrays. Fabrication with shadow masks as the patterning method instead of conventional lithography provides low-cost, time-efficient, and high-throughput InO nanoribbon biosensors without photoresist contamination. Combined with electronic enzyme-linked immunosorbent assay for signal amplification, the InO nanoribbon biosensor arrays are optimized for early, quick, and quantitative detection of cardiac biomarkers in diagnosis of acute myocardial infarction (AMI). Cardiac troponin I (cTnI), creatine kinase MB (CK-MB), and B-type natriuretic peptide (BNP) are commonly associated with heart attack and heart failure and have been selected as the target biomarkers here. Our approach can detect label-free biomarkers for concentrations down to 1 pg/mL (cTnI), 0.1 ng/mL (CK-MB), and 10 pg/mL (BNP), all of which are much lower than clinically relevant cutoff concentrations. The sample collection to result time is only 45 min, and we have further demonstrated the reusability of the sensors. With the demonstrated sensitivity, quick turnaround time, and reusability, the InO nanoribbon biosensors have shown great potential toward clinical tests for early and quick diagnosis of AMI.

Nanomaterials‐based Electrochemical Sensing of Cardiac Biomarkers for Acute Myocardial Infarction: Recent Progress

“…Cardiac TnC is not used for the diagnosis of AMI because it is not specific for heart [4]. TnI and TnT are absent in the blood of healthy people because they are released into the bloodstream due to death of the myocardial cells and this makes them important biomarkers for AMI diagnosis [6]. The cTnT is one of the well-known cardiac protein markers and is released rapidly of the contractile apparatus in cardiac muscle within 2-4 h after AMI symptoms appearance and can be kept elevated for up to 14 days, thus it is regarded as a specific and sensitive biomarker for myocardial injury diagnosis [2,48].…”

“…Creatine kinase-MB (CK-MB) is one of the biomarkers used for AMI diagnosis. CK-MB is an intracellular enzyme present in human muscles and compared to other biomarkers, its concentration in blood is relatively high [6]. As the concentration of CK-MB immediately increases after AMI and becomes unusual after 4 to 6 h, CK-MB sensing can facilitate early diagnosis of AMI [18].…”

“…Another challenge is that the electrocardiogram, the method currently used to diagnose the cardiac injuries at the emergency department, has low sensitivity and limitations [5]. The alternate strategy is the use of cardiac biomarkers because of their effectiveness to indicate pathogenic processes from different diseases [5,6].…”

High performance indium oxide nanoribbon FETs: mitigating devices signal variation from batch fabrication

“…Nanostructured FET based sensors have attracted extensive attention in chemical and biological sensing because of their direct signal transduction, exquisite sensitivity, and point-ofcare integration capability. [1][2][3][4] Preferred materials for nano FET sensors construction include silicon (Si), [5][6][7][8] oxide semiconductors, [9][10][11][12] III-V materials, [13][14][15] and carbon based materials. [16][17][18] While Si-based nanoFETs (e.g.…”

“…nanowires and nanoribbons) have been studied extensively, 6,7,[19][20][21][22] signicant recent research has focussed on semiconducting metal oxides towards better device performance and more scalable fabrication. [9][10][11][12][23][24][25][26] Of the studied oxides, In 2 O 3 displays excellent features for sensing applications. For instance, excellent sensing performance for nanoscale In 2 O 3 based FET sensors has been demonstrated for different bio/chemical/gas sensing applications.…”