Development of a highly sensitive device for counting the number of disease-specific exosomes in human sera

Yasuaki Kabe, Makoto Suematsu, Satoshi Sakamoto, Miwa Hirai, Ikko Koike, Takako Hishiki, Atsushi Matsuda, Yuichi Hasegawa, Koji Tsujita, Masayuki Ono, Naoko Minegishi, Atsushi Hozawa, Yoshinori Murakami, Michiaki Kubo, Makoto Itonaga, Hiroshi Handa

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

BACKGROUND: Although circulating exosomes in blood play crucial roles in cancer development and progression, difficulties in quantifying exosomes hamper their application for reliable clinical testing. By combining the properties of nanobeads with optical disc technology, we have developed a novel device named the ExoCounter to determine the exact number of exosomes in the sera of patients with various types of cancer. METHOD: In this system, individual exosomes were captured in the groove of an optical disc coated with antibodies against exosome surface antigens. The captured exosomes were labeled with antibody-conjugated magnetic nanobeads, and the number of the labeled exosomes was counted with an optical disc drive. RESULTS: We showed that the ExoCounter could detect specific exosomes derived from cells or human serum without any enrichment procedures. The detection sensitivity and linearity with this system were higher than those with conventional detection methods such as ELISA or flow cytometry. In addition to the ubiquitous exosome markers CD9 and CD63, the cancer-related antigens CD147, carcinoembryonic antigen, and human epidermal growth factor receptor 2 (HER2) were also used to quantify cancer cell line-derived exosomes. Furthermore, analyses of a cross-sectional cohort of sera samples revealed that HER2-positive exosomes were significantly increased in patients with breast cancer or ovarian cancer compared with healthy individuals and those with noncancer diseases. CONCLUSIONS: The ExoCounter system exhibits high performance in the direct detection of exosomes in cell culture and human sera. This method may enable reliable analysis of liquid biopsies.

Original languageEnglish
Pages (from-to)1463-1473
Number of pages11
JournalClinical Chemistry
Volume64
Issue number10
DOIs
Publication statusPublished - 01-10-2018

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Exosomes
Equipment and Supplies
CD147 Antigens
Serum
Flow cytometry
Antibodies
Biopsy
Carcinoembryonic Antigen
Surface Antigens
Cell culture
Blood
Cells
Liquids
Testing
Neoplasms
human ERBB2 protein
Ovarian Neoplasms
Flow Cytometry

All Science Journal Classification (ASJC) codes

  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Kabe, Y., Suematsu, M., Sakamoto, S., Hirai, M., Koike, I., Hishiki, T., ... Handa, H. (2018). Development of a highly sensitive device for counting the number of disease-specific exosomes in human sera. Clinical Chemistry, 64(10), 1463-1473. https://doi.org/10.1373/clinchem.2018.291963
Kabe, Yasuaki ; Suematsu, Makoto ; Sakamoto, Satoshi ; Hirai, Miwa ; Koike, Ikko ; Hishiki, Takako ; Matsuda, Atsushi ; Hasegawa, Yuichi ; Tsujita, Koji ; Ono, Masayuki ; Minegishi, Naoko ; Hozawa, Atsushi ; Murakami, Yoshinori ; Kubo, Michiaki ; Itonaga, Makoto ; Handa, Hiroshi. / Development of a highly sensitive device for counting the number of disease-specific exosomes in human sera. In: Clinical Chemistry. 2018 ; Vol. 64, No. 10. pp. 1463-1473.
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abstract = "BACKGROUND: Although circulating exosomes in blood play crucial roles in cancer development and progression, difficulties in quantifying exosomes hamper their application for reliable clinical testing. By combining the properties of nanobeads with optical disc technology, we have developed a novel device named the ExoCounter to determine the exact number of exosomes in the sera of patients with various types of cancer. METHOD: In this system, individual exosomes were captured in the groove of an optical disc coated with antibodies against exosome surface antigens. The captured exosomes were labeled with antibody-conjugated magnetic nanobeads, and the number of the labeled exosomes was counted with an optical disc drive. RESULTS: We showed that the ExoCounter could detect specific exosomes derived from cells or human serum without any enrichment procedures. The detection sensitivity and linearity with this system were higher than those with conventional detection methods such as ELISA or flow cytometry. In addition to the ubiquitous exosome markers CD9 and CD63, the cancer-related antigens CD147, carcinoembryonic antigen, and human epidermal growth factor receptor 2 (HER2) were also used to quantify cancer cell line-derived exosomes. Furthermore, analyses of a cross-sectional cohort of sera samples revealed that HER2-positive exosomes were significantly increased in patients with breast cancer or ovarian cancer compared with healthy individuals and those with noncancer diseases. CONCLUSIONS: The ExoCounter system exhibits high performance in the direct detection of exosomes in cell culture and human sera. This method may enable reliable analysis of liquid biopsies.",
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Kabe, Y, Suematsu, M, Sakamoto, S, Hirai, M, Koike, I, Hishiki, T, Matsuda, A, Hasegawa, Y, Tsujita, K, Ono, M, Minegishi, N, Hozawa, A, Murakami, Y, Kubo, M, Itonaga, M & Handa, H 2018, 'Development of a highly sensitive device for counting the number of disease-specific exosomes in human sera', Clinical Chemistry, vol. 64, no. 10, pp. 1463-1473. https://doi.org/10.1373/clinchem.2018.291963

Development of a highly sensitive device for counting the number of disease-specific exosomes in human sera. / Kabe, Yasuaki; Suematsu, Makoto; Sakamoto, Satoshi; Hirai, Miwa; Koike, Ikko; Hishiki, Takako; Matsuda, Atsushi; Hasegawa, Yuichi; Tsujita, Koji; Ono, Masayuki; Minegishi, Naoko; Hozawa, Atsushi; Murakami, Yoshinori; Kubo, Michiaki; Itonaga, Makoto; Handa, Hiroshi.

In: Clinical Chemistry, Vol. 64, No. 10, 01.10.2018, p. 1463-1473.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Development of a highly sensitive device for counting the number of disease-specific exosomes in human sera

AU - Kabe, Yasuaki

AU - Suematsu, Makoto

AU - Sakamoto, Satoshi

AU - Hirai, Miwa

AU - Koike, Ikko

AU - Hishiki, Takako

AU - Matsuda, Atsushi

AU - Hasegawa, Yuichi

AU - Tsujita, Koji

AU - Ono, Masayuki

AU - Minegishi, Naoko

AU - Hozawa, Atsushi

AU - Murakami, Yoshinori

AU - Kubo, Michiaki

AU - Itonaga, Makoto

AU - Handa, Hiroshi

PY - 2018/10/1

Y1 - 2018/10/1

N2 - BACKGROUND: Although circulating exosomes in blood play crucial roles in cancer development and progression, difficulties in quantifying exosomes hamper their application for reliable clinical testing. By combining the properties of nanobeads with optical disc technology, we have developed a novel device named the ExoCounter to determine the exact number of exosomes in the sera of patients with various types of cancer. METHOD: In this system, individual exosomes were captured in the groove of an optical disc coated with antibodies against exosome surface antigens. The captured exosomes were labeled with antibody-conjugated magnetic nanobeads, and the number of the labeled exosomes was counted with an optical disc drive. RESULTS: We showed that the ExoCounter could detect specific exosomes derived from cells or human serum without any enrichment procedures. The detection sensitivity and linearity with this system were higher than those with conventional detection methods such as ELISA or flow cytometry. In addition to the ubiquitous exosome markers CD9 and CD63, the cancer-related antigens CD147, carcinoembryonic antigen, and human epidermal growth factor receptor 2 (HER2) were also used to quantify cancer cell line-derived exosomes. Furthermore, analyses of a cross-sectional cohort of sera samples revealed that HER2-positive exosomes were significantly increased in patients with breast cancer or ovarian cancer compared with healthy individuals and those with noncancer diseases. CONCLUSIONS: The ExoCounter system exhibits high performance in the direct detection of exosomes in cell culture and human sera. This method may enable reliable analysis of liquid biopsies.

AB - BACKGROUND: Although circulating exosomes in blood play crucial roles in cancer development and progression, difficulties in quantifying exosomes hamper their application for reliable clinical testing. By combining the properties of nanobeads with optical disc technology, we have developed a novel device named the ExoCounter to determine the exact number of exosomes in the sera of patients with various types of cancer. METHOD: In this system, individual exosomes were captured in the groove of an optical disc coated with antibodies against exosome surface antigens. The captured exosomes were labeled with antibody-conjugated magnetic nanobeads, and the number of the labeled exosomes was counted with an optical disc drive. RESULTS: We showed that the ExoCounter could detect specific exosomes derived from cells or human serum without any enrichment procedures. The detection sensitivity and linearity with this system were higher than those with conventional detection methods such as ELISA or flow cytometry. In addition to the ubiquitous exosome markers CD9 and CD63, the cancer-related antigens CD147, carcinoembryonic antigen, and human epidermal growth factor receptor 2 (HER2) were also used to quantify cancer cell line-derived exosomes. Furthermore, analyses of a cross-sectional cohort of sera samples revealed that HER2-positive exosomes were significantly increased in patients with breast cancer or ovarian cancer compared with healthy individuals and those with noncancer diseases. CONCLUSIONS: The ExoCounter system exhibits high performance in the direct detection of exosomes in cell culture and human sera. This method may enable reliable analysis of liquid biopsies.

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