A non-invasive tool for early detection of acute leukemia in children using a paper-based optoelectronic nose based on an array of metallic nanoparticles

Abstract

Volatile organic compounds (VOCs) in blood samples can be used as useful biomarkers to diagnose various human diseases. This study describes the potential of a paper-based sensor array for detecting leukemia using blood VOCs. Blood samples were collected from 59 new leukemia cases and 47 healthy cases as a control group. Each blood sample was divided into two parts; one for a laboratory test and the other was used in our study. Samples were mixed with heparin and then transferred to a sterile container, and a sensor was stacked on its cap. This sensor array contains 16 nanoparticles deposited on a sheet of hydrophobic paper in a 4 × 4 array format. Containers were stored in an oven at 60 °C for 4.5 h. Then, the image of sensors was recorded by a scanner and compared to the image before exposing the blood vapor. The sensor responses were subjected to different multivariate statistical methods to develop models that discriminate between control and leukemia samples. The interaction of nanoparticles with the volatile metabolome of blood caused aggregation and consequently changing in the color of nanoparticles. The color changes resulted in a specific pattern for blood samples with leukemia, which is different from those obtained from healthy specimens. The discrimination analysis was approved by pattern recognition methods such as principal component analysis with 97% accuracy. Among 59 patients, the mean age was 6.02 ± 4.55 years (range 1–16 y). The mean total response was 652.83 ± 117.02. The rock curve showed an accuracy of 96% for classifying patients from the control group. The logistic regression model showed that 93.6% of healthy and 93.2% of patients were classified correctly by using this method. These statistics agree with the classification results obtained by principal component analysis. For every 5000-unit increase in platelet count, the chance of leukemia decreased by 9%. Additionally, the chance of being categorized as a patient decreased by 10% for every 20-unit increase in total response. The electronic nose using VOC’s of blood is a non-invasive and inexpensive tool for detecting new cases of leukemia with high sensitivity and specificity. Platelet count is an essential para-clinical parameter determining the total response of the sensors. Follow up studies with a larger sample size are warranted to elucidate its clinical applicability.