Development of a High-Throughput Automated Analyzer Using Biochip Array Technology

Abstract

Background: Use of protein array technology over conventional assay methods has advantages that include simultaneous detection of multiple analytes, reduction in sample and reagent volumes, and high output of test results. The susceptibility of ligands to denaturation, however, has impeded production of a stable, reproducible biochip platform, limiting most array assays to manual or, at most, semiautomated processing techniques. Such limitations may be overcome by novel biochip fabrication procedures. Methods: After selection of a suitable biochip substrate, biochip surfaces were chemically modified and assessed to enable optimization of biochip fabrication procedures for different test panels. The assay procedure was then automated on a dedicated instrument, and assay performance was determined for a panel of cytokine markers. Assay results were then compared with a commercial method for measurement of cytokine markers. Results: Secondary ion mass spectrometry and x-ray photoelectron spectroscopy demonstrated appropriate and reproducible modification of the biochip surface. Contact-angle studies also confirmed generation of hydrophobic surfaces that enabled containment of droplets for fabrication of discrete test regions. Automation of the biochip assays on a dedicated instrument produced excellent cytokine marker performance with intra-and interassay imprecision <10% for most analytes. Comparison studies showed good agreement with other methods (r ‫؍‬ 0.95-0.99) for cytokines. Conclusion: Performance data from this automated biochip array analyzer provide evidence that it is now possible to produce stable and reproducible biochips for output of more than 2000 test results per hour.

Risk Stratification for Heart Failure and Death in an Acute Coronary Syndrome Population Using Inflammatory Cytokines and N-Terminal Pro-Brain Natriuretic Peptide

“…This study builds on previous work by using a validated analytical platform for cytokine measurements and reference ranges for IL-8 and MCP-1 for classifying elevations (9,13 ). Moreover, the cutoffs used in this study closely resemble other reported values in the literature for risk stratification for IL-6 (26 ) and the median value for NT-proBNP in an ACS population (34 ).…”

“…In 2006, the EDTA specimens were thawed for the 1st time, and a cytokine array was measured using the evidence investigator™ (Randox) biochip platform (9,13 ). The biochip can assay 12 cytokines; however, a priori the decision was made to evaluate only IL-6, IL-8, and MCP-1 for the present study assessing HF and death in an ACS population.…”

Numerical analysis of post-impact droplet deformation for direct-print

“…Although this fundamental phenomenon has been studied for a long time, droplet impact and deformation is still an active field of research due to countless applications and the addition of various novel applications. Study of the droplet impact and deformation process for optimization and better manufacturing accuracy is required for state-ofthe-art processes, including three-dimensional (3D) cell patterning for tissue engineering (Derby, 2008;Moon et al, 2010), hybrid biological-electronic device construction, and biochip-array fabrication (FitzGerald, Lamont, McConnell, & Benchikhel, 2001), as well as traditional manufacturing (e.g., high temperature surfaces with water spray for steel making). Material jetting is one of the manufacturing technologies where the extensive study of droplet formation, dispensing, impact and deformation is essential, as the process is designed to produce a continuous or dropon-demand droplet at a high frequency.…”

Simultaneous Detection of Colorectal Cancer Mutations in Stool Samples with Biochip Arrays

“…This has implications with regards a reduction in sample/reagent consumption and as such the overall cost-effectiveness of assays. Applications of this methodology to protein and drug analysis have been previously described (20)(21)(22)(23)(24). The core of this technology is the biochip (9mm x 9mm), which represents not only the solid support, but also the vessel were hybridisation occurs.…”