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. 2022 Dec 13:17:6289-6299.
doi: 10.2147/IJN.S391234. eCollection 2022.

Dual-Channel Detection of Breast Cancer Biomarkers CA15-3 and CEA in Human Serum Using Dialysis-Silicon Nanowire Field Effect Transistor

Hang Li #  1 , Shuai Wang #  2 , Xiaosong Li  1 , Cong Cheng  3 , Xiping Shen  1 , Tong Wang  3
Affiliations

Dual-Channel Detection of Breast Cancer Biomarkers CA15-3 and CEA in Human Serum Using Dialysis-Silicon Nanowire Field Effect Transistor

Hang Li et al. Int J Nanomedicine. .

Abstract

Background: Breast cancer (BC) is the most common malignant tumors and the leading cause of cancer deaths among women. The early diagnosis and treatment of BC are effective measures that can increase survival rates and reduce mortality. Carbohydrate antigens 15-3 (CA15-3) and carcinoma embryonic antigens (CEA) have been regarded as the most two valuable tumor markers of BC. The combined detection of CA15-3 and CEA could improve the sensitivity and accuracy of early diagnosis for BC.

Methods: The multi-channel double-gate silicon nanowire field effect transistor (SiNW-FET) biosensors were fabricated by using the top-down semiconductor manufacturing technology. By surface modification of the different SiNW surfaces with monoclonal CA15-3 and CEA antibodies separately, the prepared SiNW-FET was processed into biosensor for dual-channel detection of CA15-3 and CEA.

Results: The prepared SiNW-FET biosensors were proved to have high sensitivity and specificity for the dual-channel detection of CA15-3 and CEA, and the detection limit is as low as 0.1U/mL CA15-3 and 0.01 ng/mL CEA. Moreover, the SiNW-FET biosensors were able to detect CA15-3 and CEA in serum by connecting a miniature hemodialyzer.

Conclusion: The present study reported a SiNW-FET biosensor for dual-channel detection of breast cancer biomarkers CA15-3 and CEA in serum, which has potential clinical application value for the early diagnosis and curative effect observation of BC.

Keywords: breast cancer; carbohydrate antigens 15-3; carcinoma embryonic antigens; dialysis; dual-channel detection; silicon nanowire field effect transistor.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
(A) The detection principle of SiNW-FET biosensor. (B) The principle of overcoming the Debye shielding effect by dialysis.
Figure 2
Figure 2
(A) The fabrication process for the multi-channel double-gate SiNW-FET chips. (B) The functional modification process of the SiNW surfaces.
Figure 3
Figure 3
The fabrication of PDMS dual-channel microfluidic device, and the integration of detection system. (A) Optical image of the fabricated PDMS dual-channel microfluidic device. (B) Optical image of the mold for PDMS microfluidic channels. (C) Optical image of the PDMS microfluidic device integrated with the SiNW-FET chip. (D) Optical image of the SiNW-FET biosensor integrated with acrylic fastening fixture. (E) Optical image of the miniature hemodialyzer with volume regulator. (F) Schematic diagram of the detection system.
Figure 4
Figure 4
The structure of the multi-channel double-gate SiNW-FET chip. (A) Optical image of a single SiNW-FET chip. (B) The structure diagram of dual-channel detection on SiNW-FET chip. (C) Optical microscope image of the distribution of detection region and electrodes in a single detection channel. (D) Scanning electron microscopy image of the fabricated SiNW. The width and height of SiNW is approximately 500 nm and 30 nm, respectively.
Figure 5
Figure 5
The electrical properties of the SiNW-FET chip, and the results of surface functionalization of SiNW. (A and B) The transfer and output characteristic curve of the SiNW-FET chip. (C and D) The results of surface functionalization of different SiNWs using green and red fluorescent proteins.
Figure 6
Figure 6
The specificity and sensitivity of the SiNW-FET biosensor, and the results of dual-channel detection of CA15-3 and CEA in the dialyzed serum samples. (A) Plot of current versus time when 0.5mg/mL BSA, 1U/mL CA15-3 and 1ng/mL CEA in 0.01×PBS solution were successively pumped into unmodified SiNW-FET biosensor. (B and C) Plot of current versus time for the anti-CA15-3 and anti-CEA SiNW-FET biosensor. (D) The anti-CA15-3 SiNW-FET biosensor response to different concentrations of CA15-3 in 0.01×PBS solution. (E) The anti-CEA SiNW-FET biosensor response to different concentrations of CEA in 0.01×PBS solution. (F and G) Response of the anti-CA15-3 and anti-CEA SiNW-FET biosensor to the dialyzed serum samples. ***p < 0.001. (H and I) The current change (ΔI) versus the CA15-3 and CEA concentrations in the dialyzed serum samples.
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