Multiplexed Electrochemical Cancer Diagnostics With Automated Microfluidics

Abstract

Microfluidic platforms can lead to miniaturisation, increased throughput and reduced reagent consumption, particularly when the processes are automated. Here, a programmable microcontroller is used for automation of a microfluidic platform configured to electrochemically determine the levels of 8 proteins simultaneously in complex liquid samples. The platform system is composed of a programmable Arduino microcontroller that controls inexpensive valve actuators, pump, magnetic stirrer and electronic display. The programmable microcontroller results in repeatable timing for each step in a complex assay protocol, such as sandwich immunoassays. Application of the platform is demonstrated using a multiplexed electrochemical immunoassay based on capture at the electrode surface of magnetic particles labelled with horseradish peroxidase and detection antibody. The multiplexed assay protocol is completed in less than 30 mins and results in detection of eight proteins associated with prostate cancer. The approach presented can be used to automate and simplify high‐throughput screening campaigns, such as detection of multiple biomarkers in patient samples.

Printed Electrodes in Microfluidic Arrays for Cancer Biomarker Protein Detection

“…Later, collaborations with Munge et al synthesized MBs with about 50,000 HRP enzymes, pushing LODs down to 1 fg mL −1 for interleukin 8 (IL-8) detection [ 94 ]. These studies were then extended for ultrasensitive single and multiplexed detection of cancer biomarker proteins on both SPEs and inkjet-printed electrodes coupled in microfluidic devices [ 31 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 ] ( Figure 6 ).…”

“…Their findings indicate larger surface areas hinder reaching ultrasensitive measurements and suppression of the background signal can easily be achieved by minimal surface area [ 139 ]. We have already presented many examples of signal amplification by surface modification of SPE’s by nanoparticles [ 17 , 79 , 90 , 91 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 109 , 110 , 111 ]. A few more examples are included in this section.…”

Microfluidics as an Enabling Technology for Personalized Cancer Therapy

“…For any new system to be applied in the clinic, automation of the desired protocol is highly desirable to obtain more reproducible results and to circumvent the need for highly trained staff, or prohibitively high man‐hour requirements in the running of the protocol. With this in mind, a completely automated, multiplexed electrochemical immunoassay‐based microfluidics device has been recently developed . This functions much like a traditional sandwich ELISA, except that electrochemical rather than colorimetric signal is detected when a molecule of interest binds to both the primary and secondary antibodies.…”

“…With this in mind, a completely automated, multiplexed electrochemical immunoassay-based microfluidics device has been recently developed. [71] This functions much like a traditional sandwich ELISA, except that electrochemical rather than colorimetric signal is detected when a molecule of interest binds to both the primary and secondary antibodies. This tests simultaneously for 8 proteins whose presence in blood serum is indicative of prostate cancer status.…”

Electrochemical biosensors for detection of cancer biomarkers

“…This problem can be addressed by employing multiplexed electrochemical immunoassays. 2 Multiple working electrodes or single electrode with multi-labeling of antibodies can be used. Microfluidic chips or platforms are being investigated to electrochemically determine multiple biomarkers using electrochemical detection methods.…”