Breast cancer diagnosis using a microfluidic multiplexed immunohistochemistry platform

Minseok S. Kim, Taemin Kim, Sun Young Kong, Soim Kwon, Chae Yun Bae, Jaekyu Choi, Chul Hwan Kim, Eun Sook Lee, Je Kyun Park

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Background: Biomarkers play a key role in risk assessment, assessing treatment response, and detecting recurrence and the investigation of multiple biomarkers may also prove useful in accurate prediction and prognosis of cancers. Immunohistochemistry (IHC) has been a major diagnostic tool to identify therapeutic biomarkers and to subclassify breast cancer patients. However, there is no suitable IHC platform for multiplex assay toward personalized cancer therapy. Here, we report a microfluidics-based multiplexed IHC (MMIHC) platform that significantly improves IHC performance in reduction of time and tissue consumption, quantification, consistency, sensitivity, specificity and cost-effectiveness. Methodology/Principal Findings: By creating a simple and robust interface between the device and human breast tissue samples, we not only applied conventional thin-section tissues into on-chip without any additional modification process, but also attained perfect fluid control for various solutions, without any leakage, bubble formation, or cross-contamination. Four biomarkers, estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), progesterone receptor (PR) and Ki-67, were examined simultaneously on breast cancer cells and human breast cancer tissues. The MMIHC method improved immunoreaction, reducing time and reagent consumption. Moreover, it showed the availability of semi-quantitative analysis by comparing Western blot. Concordance study proved strong consensus between conventional whole-section analysis and MMIHC (n = 105, lowest Kendall's coefficient of concordance, 0.90). To demonstrate the suitability of MMIHC for scarce samples, it was also applied successfully to tissues from needle biopsies. Conclusions/Significance: The microfluidic system, for the first time, was successfully applied to human clinical tissue samples and histopathological diagnosis was realized for breast cancers. Our results showing substantial agreement indicate that several cancer-related proteins can be simultaneously investigated on a single tumor section, giving clear advantages and technical advances over standard immunohistochemical method. This novel concept will enable histopathological diagnosis using numerous specific biomarkers at a time even for small-sized specimens, thus facilitating the individualization of cancer therapy.

Original languageEnglish
Article numbere10441
JournalPLoS One
Volume5
Issue number5
DOIs
Publication statusPublished - 2010 Sep 14

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Microfluidics
breast neoplasms
Biomarkers
immunohistochemistry
Immunohistochemistry
biomarkers
Tissue
Breast Neoplasms
neoplasms
Neoplasms
therapeutics
Microfluidic Analytical Techniques
Bubble formation
cross contamination
Biopsy
Leakage (fluid)
bubbles
Needle Biopsy
cost effectiveness
Progesterone Receptors

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Kim, M. S., Kim, T., Kong, S. Y., Kwon, S., Bae, C. Y., Choi, J., ... Park, J. K. (2010). Breast cancer diagnosis using a microfluidic multiplexed immunohistochemistry platform. PLoS One, 5(5), [e10441]. https://doi.org/10.1371/journal.pone.0010441

Breast cancer diagnosis using a microfluidic multiplexed immunohistochemistry platform. / Kim, Minseok S.; Kim, Taemin; Kong, Sun Young; Kwon, Soim; Bae, Chae Yun; Choi, Jaekyu; Kim, Chul Hwan; Lee, Eun Sook; Park, Je Kyun.

In: PLoS One, Vol. 5, No. 5, e10441, 14.09.2010.

Research output: Contribution to journalArticle

Kim, MS, Kim, T, Kong, SY, Kwon, S, Bae, CY, Choi, J, Kim, CH, Lee, ES & Park, JK 2010, 'Breast cancer diagnosis using a microfluidic multiplexed immunohistochemistry platform', PLoS One, vol. 5, no. 5, e10441. https://doi.org/10.1371/journal.pone.0010441
Kim, Minseok S. ; Kim, Taemin ; Kong, Sun Young ; Kwon, Soim ; Bae, Chae Yun ; Choi, Jaekyu ; Kim, Chul Hwan ; Lee, Eun Sook ; Park, Je Kyun. / Breast cancer diagnosis using a microfluidic multiplexed immunohistochemistry platform. In: PLoS One. 2010 ; Vol. 5, No. 5.
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