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Microfluidic Electrochemical Sensor System for Simultaneous Multi Biomarker Analyses
Published in Raju Khan, Chetna Dhand, S. K. Sanghi, Shabi Thankaraj Salammal, A. B. P. Mishra, Advanced Microfluidics-Based Point-of-Care Diagnostics, 2022
Mayank Garg, Reetu Rani, Amit L. Sharma, Suman Singh
The same group demonstrated the detection of prostate specific antigen (PSA) and prostate specific membrane antigen by employing a composite of Fe3O4 and graphene oxide with the same setup. This system exhibited an enhanced PSA detection with the limit of detection being in the fg/mL range. In yet another effort by the same research group, an electrode array with 256 sensors was developed for the detection prostate specific antigen, prostate specific membrane antigen, interleukin-6, and platelet factor-4 in the serum wherein 32 electrodes were connected to an eight-port manifold (Tang et al. 2016). This method provided high throughput for the simultaneous detection of various cancer biomarkers. Generally, for microfluidics devices, pumps are required to disperse the liquid in continuous flow manner, but the use of a pumping system increases the complexity of these devices. To overcome this, Kallempudi et al. demonstrated the use of an on-chip actuator system for the flow of the liquid on a lab-on-a-chip developed by them for the detection of human-epidermal growth factor receptor and interleukin-6. The detection limit for both the analytes was in the ng/mL range (Kallempudi et al. 2012). Six biomarkers, potentially involved in the gastric cancer, namely carcinoembryonic antigen, carbohydrate antigen 19-9, Helicobacter pylori CagA protein, P53 oncoprotein, pepsinogen I, and pepsinogen II were simultaneously detected by Xie et al. in their work (Xie et al. 2015). An array of six electrodes, with each working area modified with an antibody selective towards an analyte was used. The study claimed to achieve better sensitivity as compared to the ELISA-based method for the cancer sera that they tested. Figure 15.2 shows the microfluidic device fabricated by them. A DNA-based sensor for the detection of DNA biomarkers for bladder cancer was also reported. A sensor array of 20 electrodes was fabricated by a series of steps involving physical vapor deposition, lithography, and laser cutting. These were shown to detect the three DNA biomarkers chosen by the researcher. The limit of detection for all the biomarkers was 250 fM which is well below the amount one would find in a urine sample. The device was shown to give a reading within 20 minutes (Pursey et al. 2017).
Helicobacter pylori, stomach cancer and its prevention in New Zealand
Published in Journal of the Royal Society of New Zealand, 2020
Virginia Signal, Jason Gurney, Stephen Inns, Melissa McLeod, Dianne Sika-Paotonu, Sam Sowerbutts, Andrea Teng, Diana Sarfati
H. pylori is classed as a group one carcinogen by IARC, with the lifetime risk of stomach cancer amongst those infected with H. pylori estimated at 1%–3% (International Agency for Research on Cancer 1994). Infection of the gastric mucosa with H. pylori most commonly occurs in childhood, and can result in chronic long-lasting inflammation or gastritis. Chronic inflammation can promote gastric carcinogenesis, typically via the Correa cascade of atrophic gastritis, intestinal metaplasia, and dysplasia (Figure 2) (Correa 1996; Moss 2017). H. pylori expresses an array of proteins that interact with receptors in stomach epithelial cells, and signal cellular pathways that change the expression of genes involved in inflammation, cellular proliferation, invasion and metastasis (International Agency for Research on Cancer and World Health Organization 2014). Decades of H. pylori-related inflammation can lead to gene methylation (epigenetic changes), and chronic exposure to reactive oxygen and nitrogen species that cause DNA damage and gene mutations leading to the development of cancer (International Agency for Research on Cancer and World Health Organization 2014). H. pylori virulence factors such as cytotoxin-associated gene A (CagA), vacuolating cytotoxin (VacA), or lipopolysaccharide (LPS) also play a role in carcinogenesis by modulating cellular signalling pathways (International Agency for Research on Cancer and World Health Organization 2014). For example, it is known that CagA positive H. pylori increases the risk of stomach cancer more than the Cag-A negative H. pylori strain (Huang et al. 2003). Additionally, different CagA subtypes carry differing risks of cancer. The Eastern strains prevalent in Asia, and in Māori (Fraser 2004) are more pathogenic than Western strains (Yuan et al. 2017). Ethnic differences in the virulence strains of H. pylori may contribute to the Māori/non-Māori stomach cancer incidence gap, although the current pattern of virulence factors in New Zealand is unknown.