Antifouling Electrochemical Biosensor Based on the Designed Functional Peptide and the Electrodeposited Conducting Polymer for CTC Analysis in Human Blood

Abstract

Circulating tumor cells (CTCs) are considered reliable cancer biomarkers for the liquid biopsy of many types of tumors. The direct detection of CTCs in human blood with normal biosensors, however, remains challenging because of severe biofouling in blood that contains various proteins and a large number of cells. Herein, we report the construction of an antifouling electrochemical biosensor capable of assaying CTCs directly in blood, based on a designed multifunctional peptide and the electrodeposited conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT). The designed peptide possesses antifouling capability in complex biological media and specific recognition ability to capture breast cancer cells MCF-7. Meanwhile, electrodeposited PEDOT can promote electron transfer at the sensing interface, improve the signal-to-noise ratio for the detection, and thus enhance the sensitivity of the biosensor. The integration of the multifunctional peptide and conducting polymer PEDOT ensures that the developed biosensor is able to perform directly in blood samples without purification or separation. The antifouling electrochemical biosensor for the detection of MCF-7 cells exhibits a wide linear range over 4 orders, with a limit of detection (LOD) of 17 cells mL −1 . More interestingly, even when performing in 25% human blood, the biosensor still retains a linear response with an LOD of 22 cells mL −1 , without suffering significantly from biofouling in real blood. This work provides a promising strategy for the direct analysis of CTCs in human blood without a complicated pretreatment, and it may find practical application in the liquid biopsy of cancers.

A multifunctional black phosphorus nanosheet-based immunomagnetic bio-interface for heterogeneous circulating tumor cell capture and simultaneous self-identification in gastric cancer patients

“…[3][4][5][6] However, since the number of CTCs in blood is extremely small, how to successfully and reliably capture them from the complex blood media is a critical step for downstream analysis. [7][8][9][10][11][12] Compared with the common capture methods established according to some physical properties, such as cell size, 13 density, 14 and permittivity, 15 an affinity-based strategy is more popularly employed in CTC isolation, taking advantage of the specific interactions between the recognition ligands (antibody, 16 aptamer, 17 peptide, 18 etc.) on the capture interface and the biomarkers on the CTC membrane.…”

Sulfonated Starch-Graft-Polyaniline@Graphene Electrically Conductive Nanocomposite: Application for Tyrosinase Immobilization

“…), in the design of various electrochemical biosensors. [ 20 , 21 , 22 ]. In this regard, we designed a biocompatible nanocomposite from sulfonated starch grafted to polyaniline and graphene for the immobilization of tyrosinase.…”

“…Moreover, PANI displays two redox couples which ease the charge transfer between an enzyme and a polymer. Due to the great electrochemical properties along with in vivo biocompatibility, PANI-based nanocomposites can be used to detect a negligible amount of biomolecules with high sensitivities and fast responses [ 18 , 19 , 20 , 21 , 22 ]. To enhance the good immobilization of enzymes on the PANI, the copolymerization method with functionalized monomers and/or modified natural polymers can be used.…”

The design of anti-fouling and anti-hydrolysis cyclic peptides for accurate electrochemical antigen testing in human blood

“…15 Many specifically designed peptides have been reported to be of good antifouling properties. [19][20][21][22] Among these, linear peptides have been most widely and intensively studied, and for the synthesis of linear peptides, both liquid-phase and solid-phase methods have been well established. 23 Although many linear peptides have good biological activity and stability in vitro, they get degraded quickly after contacting with the biological media due to the presence of various protein hydrolases (such as endopeptidase and exopeptidase), leading to the loss of activity.…”