Abstract

The detection of myoglobin (Myo), cardiac troponin I (cTnI), creatine kinase-MB (CK-MB), and b-type natriuretic peptide (BNP) plays a vital role in diagnosing cardiovascular diseases. Here we present single site-specific polyaniline (PANI) nanowire biosensors that can detect cardiac biomarkers such as Myo, cTnI, CK-MB, and BNP with ultra-high sensitivity and good specificity. Using single PANI nanowire-based biosensors integrated with microfluidic channels, very low concentrations of Myo (100 pg/mL), cTnI (250 fg/mL), CK-MB (150 fg/mL), and BNP (50 fg/mL) were detected. The single PANI nanowire-based biosensors displayed linear sensing profiles for concentrations ranging from hundreds (fg/mL) to tens (ng/mL). In addition, devices showed a fast (few minutes) response satisfying respective reference conditions for Myo, cTnI, CK-MB, and BNP diagnosis of heart failure and for determining the stage of the disease. This single PANI nanowire-based biosensor demonstrated superior biosensing reliability with the feasibility of label free detection and improved processing cost efficiency due to good biocompatibility of PANI to monoclonal antibodies (mAbs). Therefore, this development of single PANI nanowire-based biosensors can be applied to other biosensors for cancer or other diseases.

Highlights

  • The incidence of myocardial infarction, which has one of the highest mortality rates in the US and Europe, increases in elderly people [1,2]

  • Nanowire biosensor to detect cardiac biomarkers. (a) The experimental setup; the microfluidic channel is adhered on the nanowire biosensor and the nanowire biosensor chip is mounted on a probe station connected to the semiconductor analyzer and syringe pump with inlet and outlet; (b) The conductance change in the single PANI nanowire-based biosensor is monitored

  • The same single PANI nanowires were compared by scanning electron microscopy (SEM) before and after the surface immobilization of monoclonal antibodies (mAbs) to observe the change of nanowire surfaces as shown in

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Summary

Introduction

The incidence of myocardial infarction, which has one of the highest mortality rates in the US and Europe, increases in elderly people [1,2]. For the detection of myocardial infarction, myoglobin (Myo), cardiac troponin I (cTnI), creatine kinase-MB (CK-MB), and b-type natriuretic peptide (BNP) have been selected as biomarkers for the diagnosis [1,3,4]. They have relatively lower sensitivity and specificity than nanomaterial-based biosensors such as nanoparticles, carbon nanotubes (CNTs), and nanowires [16,17,18] Those nanomaterials provide outstanding physical properties such as tunable conductivity by doping and synthesis methods, and high carrier mobility to realize real-time sensing in 0- or 1-dimensional structure [19,20]. We report the development of single PANI nanowire-based biosensors for detecting four cardiac biomarkers: Myo, cTnI, CK-MB, or BNP. Integration of microfluidic channels on the nanowire biosensors allows more accurate sensing and slow flow of sample solution only through the active area of the PANI nanowire [38]

Materials
Fabrication of Single PANI Nanowire
Functionalization of Single PANI Nanowire
Preparation of Microfluidic Channel
Detection of Target Proteins on the Nanowire Biosensor
Functionalization of Single PANI Nanowires with mAbs
Detection of Cardiac Biomarkers
Effect of Net Surface Charge on the Single PANI Nanowire Biosensor
Conclusions

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