Ultrasensitive Label‐free Electrochemical Immunosensors for Multiple Cell Surface Biomarkers on Liver Cancer Stem Cells

Abstract

Liver cancer is one of the most widely spread cancers in the world. Cancer stem cells (CSCs) are a small subpopulation of liver cancer cells that are thought to be responsible for relapse of cancer and the resistance to chemotherapy. Detection of CSCs is highly demanded for screening patients who are at high risk for developing metastatic cancers. However, the current methodologies for CSCs detection are sophisticated, expensive and not reliable. Here, we report the development of a label‐free impedance immunosensors for liver CSC quantification using four established CSC surface biomarkers (CD44, CD90, CD133/2 and OV‐6). The immunosensors were simply fabricated by the covalent attachment of four biomarkers specific antibodies on gold electrodes using cysteamine/phenylene isothiocyanate linker. Electrochemical impedance spectroscopy was employed to detect the binding of the cells to the immunosensors. The binding of the CSCs to the gold electrode surface retards the access of ferri‐ferrocyanide redox molecules to the electrode leading to enhancement in the charge transfer resistance (Rct) which represents the basis of the detection signal. The developed electrochemical immunosensors showed high sensitivity and selectivity for CSC detection with a wide linear range from 1 × 101 to 1× 104 cells/mL with a limit of detection of 1 cell/ml. This work represents a new, accurate, simple and low cost method for the detection of liver CSC that might help in the early diagnosis of metastatic disease and cancer relapse.

Smart nanomaterials for cancer diagnosis and treatment

“…In studies, YYYYC was conjugated to myelopeptide-4, which is derived from bone marrow and fixed on electrode through collagen and measured through electrochemical impedance spectroscopy [ 193 ]. Additionally, the electrochemical nanosensors were utilized to detect the cancer stem cell which predominantly expresses the cell surface markers CD44, CD90, CD133/2, and OV-6 through their antibodies of gold electrodes [ 194 ]. Molecular frameworks (Cr-MOF) were also popularly utilised for detection of the CT26 colorectal cancers [ 195 ].…”

Electrochemical Sensors for Detection of Markers on Tumor Cells

“…Cancer stem cells (CSCs) are thought to be responsible for cancer recurrence and resistance to chemotherapy [ 52 ]. Eissa’s group reported on a label-free impedance cell-based biosensor using antibodies specific to four established tumor stem cell surface biomarkers (CD44, CD90, CD133/2, and OV-6) [ 53 ]. Cysteamine–phenylene isothiocyanate was used to attach the antibody to a gold electrode to capture the CSCs.…”

Silica nanoparticle assists determining liver cancer gene sequence on interdigitated electrode surface

“…This result confirms that the system shown in this study did not show biofouling and it specifically recognizes the targeted DNA sequence. The current demonstration with DNA sensor has added up for high performance to the currently available DNA sensors (Table 1) [25][26][27][28][29][30][31].…”