A 1024-sample serum analyzer chip for cancer diagnostics

Abstract

We present a platform that combines microarrays and microfluidic techniques to measure four protein biomarkers in 1024 serum samples for a total of 4096 assays per device. Detection is based on a surface fluorescence sandwich immunoassay with a limit of detection of~1 pM for most of the proteins measured: PSA, TNF-α, IL-1β, and IL-6. To validate the utility of our platform, we measured these four biomarkers in 20 clinical human serum samples, 10 from prostate cancer patients and 10 female and male controls. We compared the results of our platform to a conventional ELISA and found a good correlation between them. However, compared to a classical ELISA, our device reduces the total cost of reagents by 4 orders of magnitude while increasing throughput by 2 orders of magnitude. Overall, we demonstrate an integrated approach to perform low-cost and rapid quantification of protein biomarkers from over one thousand serum samples. This new high-throughput technology will have a significant impact on disease diagnosis and management.

Rapid, automated, parallel quantitative immunoassays using highly integrated microfluidics and AlphaLISA

“…To address these limitations, different microfluidic immunoassay platforms have been developed in the past with different levels of success for quantitative measurements of protein biomarkers in biological samples showing good correlations and comparable sensitivities to conventional ELISA141516171819202122. However, majority of these microfluidic immunoassay chips still utilize heterogeneous sandwich immunoassays for biodetection, necessitating immobilized capture antibodies on a solid phase and multiple washing, labeling, and signal amplification steps that can increase assay complexity and time and result variation.…”

“…Highly integrated microfluidics has been successfully applied in different chemical and biomedical applications, such as single-cell genomic and proteomic analysis78, stem cell culture91011, and drug screening assays1213. Nonetheless, till now, only a handful of integrated microfluidic platforms have been developed that can achieve automated, multiplex immunoassays entirely on-chip without any off-chip interventions141516171819202122. Majority of these integrated microfluidic immunoassay chips rely on heterogeneous sandwich immunoassays for generating biosensing signals.…”

“…Majority of these integrated microfluidic immunoassay chips rely on heterogeneous sandwich immunoassays for generating biosensing signals. While achieving a limit of detection (LOD) comparable to conventional ELISA, these integrated microfluidic immunoassay chips still require immobilizing capture antibodies on a solid phase and multiple washing, labeling, and signal amplification steps, retaining limitations associated with conventional ELISA in terms of assay complexity and time141516171819202122.…”

Mechanically Induced Trapping of Molecular Interactions and Its Applications

“…The device can detect and measure up to four biomarkers for each sample for a total of 4096 assays on a chip. Reprinted from Garcia-Cordero, 23 by permission of the Royal Society of Chemistry.…”

Creating Isolated Liquid Compartments Using Photopatterned Obstacles in Microfluidics

“…For instance, isolated nanoliter water pockets in a microchannel, much like a multiwell plate system, can be used for applications in diagnostics, drug discovery, and hydrogel synthesis [1][2][3][4][5]. Similarly, entrapped oil pockets can be used to study reaction engineering and to screen chemicals for enhanced oil recovery [6].…”