Detection of HER2 breast cancer biomarker using the opto-fluidic ring resonator biosensor

Protein biomarkers have recently been heavily researched in their roles in the detection, quantification, and monitoring of aggressive types of breast cancer. In this work, we describe a novel, label-free approach for detecting the HER2 extra-cellular domain breast cancer biomarker in human serum samples using the opto-fluidic ring resonator (OFRR). The OFRR incorporates microfluidics and optical ring resonator sensing technology to achieve rapid label-free detection in a small and low-cost platform. In this study, HER2 proteins were spiked in serum at varying concentrations. Results show that the OFRR is able to detect HER2 at medically relevant concentrations in serum ranging from 13 to 100 ng/mL in 30 min. Our work will lead to a device that can be used as a tool for monitoring disease progression in a low-cost sensing setup.

[1]  A. M. Stanley,et al.  Structure of the extracellular region of HER 2 alone and in complex with the Herceptin Fab , 2022 .

[2]  G. Condorelli,et al.  Cardiotoxic effects, or lack thereof, of anti‐ErbB2 immunoagents , 2009, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[3]  H. Chenga,et al.  Automated breast cancer detection and classification using ultrasound images A survey , 2009 .

[4]  Xudong Fan,et al.  PDMS embedded opto-fluidic microring resonator lasers. , 2008, Optics express.

[5]  A. Jemal,et al.  Cancer Statistics, 2006 , 2006, CA: a cancer journal for clinicians.

[6]  T. Fleming,et al.  Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. , 2001, The New England journal of medicine.

[7]  L. C. Gunn,et al.  Label-free quantitation of a cancer biomarker in complex media using silicon photonic microring resonators. , 2009, Analytical chemistry.

[8]  Anne J. Kearney,et al.  Breast cancer screening recommendations: is mammography the only answer? , 2009, Journal of midwifery & women's health.

[9]  M. Douglas LeVan,et al.  Binary Langmuir and Freundlich isotherms for ideal adsorbed solutions , 1981 .

[10]  M K Schwartz,et al.  Breast cancer marker Ca549. A multicenter study. , 1994, American journal of clinical pathology.

[11]  Dieter Braun,et al.  Protein detection by optical shift of a resonant microcavity , 2002 .

[12]  Hongying Zhu,et al.  Rapid and label-free detection of breast cancer biomarker CA15-3 in clinical human serum samples with optofluidic ring resonator sensors. , 2009, Analytical chemistry.

[13]  R. Neumann,et al.  Evaluation of the quantitative analytical methods real-time PCR for HER-2 gene quantification and ELISA of serum HER-2 protein and comparison with fluorescence in situ hybridization and immunohistochemistry for determining HER-2 status in breast cancer patients. , 2005, Clinical chemistry.

[14]  C. Vogel,et al.  Evaluation of clinical outcomes according to HER2 detection by fluorescence in situ hybridization in women with metastatic breast cancer treated with trastuzumab. , 2005, Clinical breast cancer.

[15]  Wan Y. Shih,et al.  Label-free, all-electrical, in situ human epidermal growth receptor 2 detection. , 2008, The Review of scientific instruments.

[16]  Xudong Fan,et al.  Liquid-core optical ring-resonator sensors. , 2006, Optics letters.

[17]  Hongying Zhu,et al.  Label-free quantitative DNA detection using the liquid core optical ring resonator. , 2008, Biosensors & bioelectronics.

[18]  Yuze Sun,et al.  Sensitive optical biosensors for unlabeled targets: a review. , 2008, Analytica chimica acta.

[19]  P. Pilarski,et al.  FISH and chips: chromosomal analysis on microfluidic platforms. , 2007, IET nanobiotechnology.

[20]  S. Hanash,et al.  Comparative study of SPR and ELISA methods based on analysis of CD166/ALCAM levels in cancer and control human sera. , 2009, Biosensors & bioelectronics.

[21]  W. Gullick Update on HER-2 as a target for cancer therapy: Alternative strategies for targeting the epidermal growth factor system in cancer , 2001, Breast Cancer Research.

[22]  Hongying Zhu,et al.  Analysis of biomolecule detection with optofluidic ring resonator sensors. , 2007, Optics express.

[23]  Irving Langmuir THE CONSTITUTION AND FUNDAMENTAL PROPERTIES OF SOLIDS AND LIQUIDS. PART I. SOLIDS. , 1916 .

[24]  J A Ramos-Vara,et al.  Technical Aspects of Immunohistochemistry , 2005, Veterinary pathology.

[25]  J. Pyun,et al.  Additive assay of cancer marker CA 19-9 by SPR biosensor , 2006 .

[26]  Abraham J. Qavi,et al.  Label-free technologies for quantitative multiparameter biological analysis , 2009, Analytical and bioanalytical chemistry.

[27]  John Gohring,et al.  SERS-based detection in an optofluidic ring resonator platform. , 2007, Optics express.

[28]  Aurel Ymeti,et al.  An ultrasensitive Young interferometer handheld sensor for rapid virus detection , 2007, Expert review of medical devices.

[29]  Xudong Fan,et al.  Advanced photonic structures for biological and chemical detection , 2009 .

[30]  Hongying Zhu,et al.  Opto-fluidic micro-ring resonator for sensitive label-free viral detection. , 2008, The Analyst.

[31]  Ling Zhang,et al.  Automated breast cancer detection and classification using ultrasound images: A survey , 2015, Pattern Recognit..

[32]  A Densmore,et al.  Silicon photonic wire biosensor array for multiplexed real-time and label-free molecular detection. , 2009, Optics letters.

[33]  Salvador Alegret,et al.  Integrated Analytical Systems , 2003 .

[34]  Ming Zhao,et al.  Prostate-specific antigen immunoassays on the BioCD , 2009, Analytical and bioanalytical chemistry.

[35]  Harshini Mukundan,et al.  Planar optical waveguide-based biosensor for the quantitative detection of tumor markers , 2009 .