Printed Electrodes in Microfluidic Arrays for Cancer Biomarker Protein Detection

Abstract

Medical diagnostics is trending towards a more personalized future approach in which multiple tests can be digitized into patient records. In cancer diagnostics, patients can be tested for individual protein and genomic biomarkers that detect cancers at very early stages and also be used to monitor cancer progression or remission during therapy. These data can then be incorporated into patient records that could be easily accessed on a cell phone by a health care professional or the patients themselves on demand. Data on protein biomarkers have a large potential to be measured in point-of-care devices, particularly diagnostic panels that could provide a continually updated, personalized record of a disease like cancer. Electrochemical immunoassays have been popular among protein detection methods due to their inherent high sensitivity and ease of coupling with screen-printed and inkjet-printed electrodes. Integrated chips featuring these kinds of electrodes can be built at low cost and designed for ease of automation. Enzyme-linked immunosorbent assay (ELISA) features are adopted in most of these ultrasensitive detection systems, with microfluidics allowing easy manipulation and good fluid dynamics to deliver reagents and detect the desired proteins. Several of these ultrasensitive systems have detected biomarker panels ranging from four to eight proteins, which in many cases when a specific cancer is suspected may be sufficient. However, a grand challenge lies in engineering microfluidic-printed electrode devices for the simultaneous detection of larger protein panels (e.g., 50–100) that could be used to test for many types of cancers, as well as other diseases for truly personalized care.

Immunoarray Measurements of Parathyroid Hormone-Related Peptides Combined with Other Biomarkers to Diagnose Aggressive Prostate Cancer

“…25 Although such low LODs were not specifically required for this study, the low LODs allow trading off sensitivity for fast assay times while still minimizing Ab-cross reactivities and NSB by high dilution of samples. 55,56 Good reproducibility is indicated by small error bars. All PTHrP fragments showed excellent sensitivities in linear dynamic ranges from 7.69 to 13.87 μA cm −2 [log C] −1 .…”

“…High sensitivities and S/N ratios and ultralow LODs are due to large signal amplification from (i) optimization reagent concentrations, NSB lowering, flow rates, and incubation times, (ii) the dual catalytic redox cycle where (Figure S4) 400 HRPFe III in poly-HRP are oxidized to HRPFe IV O by H 2 O 2 to be subsequently electrocatalytically reduced via an HQ mediator, and (iii) use of GSH-AuNPs to increase surface area for antibody binding and also enhance electron transfer . The immunoarray reaches ultralow LODs not specifically needed for this study but allows trading sensitivity for assay speed and enables high sample dilution to minimize NSB and antibody cross-reactivity. , Our results are in concert with PTHrPs having a high potential for identifying aggressive prostate cancers. Analysis of PTHrPs in prostate cancer patient sera is the first attempt to evaluate PTHrP fragments as potential biomarkers for aggressive prostate cancer in a large pool of patients, whereas most prior studies focused on PTHrP detection in cell lines and tumor biopsies. ,− …”

Microfluidic systems for the analysis of blood‐derived molecular biomarkers

“…However, one of the main challenges is that during the early stages of the disease, protein biomarkers are present at very low levels [222,273]. The poor sensitivity of conventional analytical techniques makes the detection of low-abundance biomarkers from a complex and heterogenous sample (e.g., serum or plasma) rather challenging [273,274]. Therefore, two strategies have been used to improve the detection of low-abundance proteins.…”

A compact, low-cost, and binary sensing (BiSense) platform for noise-free and self-validated impedimetric detection of COVID-19 infected patients

“…Multiplex electrochemical point-of-care testing (ME-POCT) devices are expected to have four major compartments: 1) reliable and reproducible electrodes created using inkjet or screen printing methods, 2) an accurate biosensing protocol for mediating the electrode surface to create accurate biosensors, 3) microfluidics for automating electrochemical biosensing steps, and 4) and an accurate and low-cost multichannel potentiostat with an easy-to-use interface for data interpretation and wireless data transfer. Despite enormous advances in developing multiplex screen printed electrodes and electrochemical biosensors ( Dhanapala et al, 2020 ; Khetani et al, 2019 ; Kinnamon et al, 2018 ; Noah and Ndangili, 2019 ; Salahandish et al 2019 , 2022a ) as well as the recent progress in self-powered microfluidic devices ( Haghayegh et al 2022a , 2022b ; Nyein et al, 2018 ; Salahandish et al, 2022b ), the realization of ME-POCT requires the development of new hand-held, rapid and remote reading, easy-to-use, noise-free, and cheaper multichannel potentiostat readers ( Alam et al, 2020 ; Bianchi et al, 2021 ).…”