High sensitivity detection of a protein biomarker interleukin-8 utilizing a magnetic modulation biosensing system

Abstract Biomarkers are an important component of medical diagnosis and patient management. There is an ongoing need for accurate, precise, and reproducible methods to detect and quantify biomarkers to help diagnose diseases. High-sensitivity assays for biomarker measurements have been developed to address this need, but they are usually done in laboratories, using complex and expensive equipment that allows for high throughput testing. To enable health care providers to make more timely decisions, biomarker measurement can be performed at the patient’s bedside, but the devices used in these settings are associated with less precise and less sensitive performance. The solution is a small footprint technology that enables more sensitive measurement of biomarkers, using simple instrumentation. Here, we utilize a novel diagnostic platform, named Magnetic Modulation Biosensing (MMB), and demonstrate its capabilities in high-sensitivity biomarker detection. MMB uniquely combines magnetic and fluorescent labeling to measure ultra-low biomarker concentrations. We demonstrate the system’s capabilities using a commercially-available assay for detection and quantification of human Interleukin-8 over several orders of magnitude. The results show that MMB has a 6-log dynamic range available for detection and is capable of detecting 0.08 ng/L of IL-8 in blood plasma, a sensitivity comparable to current state-of-the-art laboratory assays.

[1]  A. Arie,et al.  Detection of fluorescent-labeled probes at subpicomolar concentrations by magnetic modulation. , 2008, Optics express.

[2]  Nicole Pamme,et al.  Mobile magnetic particles as solid-supports for rapid surface-based bioanalysis in continuous flow. , 2009, Lab on a chip.

[3]  Hsin-Chih Yeh,et al.  Single-molecule detection and probe strategies for rapid and ultrasensitive genomic detection. , 2005, Current pharmaceutical biotechnology.

[4]  Jasenka Verbarg,et al.  Spinning magnetic trap for automated microfluidic assay systems. , 2012, Lab on a chip.

[5]  Frances S. Ligler,et al.  Catch and release: integrated system for multiplexed detection of bacteria. , 2013, Analytical chemistry.

[6]  A. Arie,et al.  Rapid homogenous detection of the Ibaraki virus NS3 cDNA at picomolar concentrations by magnetic modulation. , 2009, Biosensors & bioelectronics.

[7]  Michael A Daniele,et al.  3D hydrodynamic focusing microfluidics for emerging sensing technologies. , 2015, Biosensors & bioelectronics.

[8]  H. Baker,et al.  Conversion of a capture ELISA to a Luminex xMAP assay using a multiplex antibody screening method. , 2012, Journal of Visualized Experiments.

[9]  Sheila A. Grant,et al.  Electrospun sol-gel fibers for fluorescence-based sensing , 2009, Defense + Commercial Sensing.

[10]  Manoj M. Varma,et al.  Performance limitations of label-free sensors in molecular diagnosis using complex samples , 2016, SPIE BiOS.

[11]  R. Peters,et al.  IL-8 Plasma Concentrations and the Risk of Future Coronary Artery Disease in Apparently Healthy Men and Women: The EPIC-Norfolk Prospective Population Study , 2004, Arteriosclerosis, thrombosis, and vascular biology.

[12]  Ara Darzi,et al.  Preparing for precision medicine. , 2012, The New England journal of medicine.

[13]  Frances S. Ligler,et al.  Signal amplification strategies for microfluidic immunoassays , 2016 .

[14]  D. Morrow,et al.  Earlier detection of myocardial injury in a preliminary evaluation using a new troponin I assay with improved sensitivity. , 2007, American journal of clinical pathology.

[15]  L. Monasta,et al.  Cytokine Levels in the Serum of Healthy Subjects , 2013, Mediators of inflammation.

[16]  M. Vellekoop,et al.  Characterization of a microflow cytometer with an integrated three-dimensional optofluidic lens system. , 2010, Biomicrofluidics.