One-Shot Full-Range Quantification of Multi-Biomarkers With Different Abundance by a Tandem Giant Magnetoresistance Assay

In this study, we reported a tandem giant magnetoresistance (GMR) assay that realized the one-shot quantification of multi-biomarkers of infection, C-reactive protein (CRP) with procalcitonin (PCT), and neutrophil gelatinase-associated lipocalin (NGAL), all of which could cover their clinically relevant concentration ranges under a different principle. In the presence of co-determined assay, we quantified these three biomarkers in undiluted human blood serum in a single test. The tandem principle, based on which quantification of CRP occurs, combines a sandwich assay and an indirect competitive assay, which allows for the discrimination of the concentration values resulting from the multivalued dose-response curve (\u27Hook\u27 effect), which characterizes the one-step sandwich assay at high CRP concentrations. However, the entire diagnostically dynamic range, in the quantification of PCT and NGAL, was achieved by differential coating of two identical GMR sensors operated in tandem and by combining two standard curves. The sensor quantified low detection limits and a broader dynamic range for the detection of infection biomarkers. The noticeable features of the assay are its dynamic range and small sample volume requirement (50 mu L), and the need for a short measurement time of 15 min. These figures of merit render it a prospective candidate for practical use in point-of-care analysis

A tandem giant magnetoresistance assay for one-shot quantification of clinically relevant concentrations of N-terminal pro-B-type natriuretic peptide in human blood

We report a microfluidic sandwich immunoassay constructed around a dual-giant magnetoresistance (GMR) sensor array to quantify the heart failure biomarker NT-proBNP in human plasma at the clinically relevant concentration levels between 15\ua0pg/mL and 40\ua0ng/mL. The broad dynamic range was achieved by differential coating of two identical GMR sensors operated in tandem, and combining two standard curves. The detection limit was determined as 5\ua0pg/mL. The assay, involving 53 plasma samples from patients with different cardiovascular diseases, was validated against the Roche Cobas e411 analyzer. The salient features of this system are its wide concentration range, low detection limit, small sample volume requirement (50\ua0μL), and the need for a short measurement time of 15\ua0min, making it a prospective candidate for practical use in point of care analysis

Dynamic Range Expansion of the C-Reactive Protein Quantification with a Tandem Giant Magnetoresistance Biosensor

In this study, we report a convenient analytical method for a full-range quantification of the C-reactive protein (CRP), a blood biomarker of infection and cardiovascular events. We determine CRP over the entire diagnostically relevant concentration range in undiluted human blood serum in a single test, using a tandem giant magnetoresistance (GMR) sensor. The tandem principle combines a sandwich assay and a competitive assay, which allows for the discrimination of the concentration values resulting from the multivalued dose-response curve ("Hook"effect), which characterizes the one-step sandwich assay at high CRP concentrations. The sensor covers a linear detection range for CRP concentration from 3 ng/mL to 350 μg/mL, the detection limit (s/n = 3) is 1 ng/mL. The prominent features of the chip-based method are its expanded dynamic range and low sample volume (50 μL), and the need for a short measurement time of 15 min. These figures of merit, in addition to the low detection limit equal to the established assay instrumentation, make it a viable candidate for use in point-of-care diagnostics

Silicon-based Integrated Microarray Biochips for Biosensing and Biodetection Applications

The silicon-based integrated microarray biochip (IMB) is an inter-disciplinary research direction of microelectronics and biological science. It has caught the attention of both industry and academia, in applications such as deoxyribonucleic acid (DNA) and immunological detection, medical inspection and point-of-care (PoC) diagnosis, as well as food safety and environmental surveillance. Future biodetection strategies demand biochips with high sensitivity, miniaturization, integration, parallel, multi-target and even intelligence capabilities. In this chapter, a comprehensive investigation of current research on state-of-the-art silicon-based integrated microarray biochips is presented. These include the electrochemical biochip, magnetic tunnelling junction (MTJ) based biochip, giant magnetoresistance (GMR) biochip and integrated oscillator-based biochip. The principles, methodologies and challenges of the aforementioned biochips will also be discussed and compared from all aspects, e.g., sensitivity, fabrication complexity and cost, compatibility with silicon-based complementary metal-oxide-semiconductor (CMOS) technology, multi-target detection capabilities, signal processing and system integrations, etc. In this way, we discuss future silicon-based fully integrated biochips, which could be used for portable medical detection and low cost PoC diagnosis applications

KOBAS 2.0: a web server for annotation and identification of enriched pathways and diseases

High-throughput experimental technologies often identify dozens to hundreds of genes related to, or changed in, a biological or pathological process. From these genes one wants to identify biological pathways that may be involved and diseases that may be implicated. Here, we report a web server, KOBAS 2.0, which annotates an input set of genes with putative pathways and disease relationships based on mapping to genes with known annotations. It allows for both ID mapping and cross-species sequence similarity mapping. It then performs statistical tests to identify statistically significantly enriched pathways and diseases. KOBAS 2.0 incorporates knowledge across 1327 species from 5 pathway databases (KEGG PATHWAY, PID, BioCyc, Reactome and Panther) and 5 human disease databases (OMIM, KEGG DISEASE, FunDO, GAD and NHGRI GWAS Catalog). KOBAS 2.0 can be accessed at http://kobas.cbi.pku.edu.cn

SEAS: A System for SEED-Based Pathway Enrichment Analysis

Pathway enrichment analysis represents a key technique for analyzing high-throughput omic data, and it can help to link individual genes or proteins found to be differentially expressed under specific conditions to well-understood biological pathways. We present here a computational tool, SEAS, for pathway enrichment analysis over a given set of genes in a specified organism against the pathways (or subsystems) in the SEED database, a popular pathway database for bacteria. SEAS maps a given set of genes of a bacterium to pathway genes covered by SEED through gene ID and/or orthology mapping, and then calculates the statistical significance of the enrichment of each relevant SEED pathway by the mapped genes. Our evaluation of SEAS indicates that the program provides highly reliable pathway mapping results and identifies more organism-specific pathways than similar existing programs. SEAS is publicly released under the GPL license agreement and freely available at http://csbl.bmb.uga.edu/~xizeng/research/seas/

Dynamic Range Expansion of the C-Reactive Protein Quantification with a Tandem Giant Magnetoresistance Biosensor

In this study, we report a convenient analytical method for a full-range quantification of the C-reactive protein (CRP), a blood biomarker of infection and cardiovascular events. We determine CRP over the entire diagnostically relevant concentration range in undiluted human blood serum in a single test, using a tandem giant magnetoresistance (GMR) sensor. The tandem principle combines a sandwich assay and a competitive assay, which allows for the discrimination of the concentration values resulting from the multivalued dose-response curve ("Hook"effect), which characterizes the one-step sandwich assay at high CRP concentrations. The sensor covers a linear detection range for CRP concentration from 3 ng/mL to 350 μg/mL, the detection limit (s/n = 3) is 1 ng/mL. The prominent features of the chip-based method are its expanded dynamic range and low sample volume (50 μL), and the need for a short measurement time of 15 min. These figures of merit, in addition to the low detection limit equal to the established assay instrumentation, make it a viable candidate for use in point-of-care diagnostics