Clinical Application for Screening Down's Syndrome by Using Carboxylated Graphene Oxide-Based Surface Plasmon Resonance Aptasensors

Int J Nanomedicine. 2020 Oct 22:15:8131-8149. doi: 10.2147/IJN.S270938. eCollection 2020.

Abstract

Background: Advanced medical detection technology requires high sensitivity and accuracy to increase the disease detection rate. We showed that carboxyl-functionalized graphene oxide (carboxyl-GO) biosensing materials are capable of accurate detection.

Methods: We developed a carboxylated GO-based surface plasmon resonance (SPR) aptasensor suitable for screening Down's syndrome in clinical serum. This biosensing material could rapidly and accurately detect hCG protein with a low concentration to identify fetal Down's syndrome. The developed carboxyl-GO-based SPR aptasensor showed excellent sensitivity and limit of detection without the use of antibodies and without any specific preference.

Results: hCG protein detection limits of 1 pM in buffer samples and 1.9 pM in clinical serum samples were achieved. The results showed that the carboxyl-GO-based chip could detect hCG well below the normal physiological level of serum protein (5.0 mIU/mL). High affinity, sensitivity, and better detection limit were obtained in the range of 1.9 pM to 135 pM. The results showed a 5k-fold dilution factor, and that an SPR angle shift of more than 20 millidegrees (mo) was associated with a significant risk of fetal Down's syndrome compared to normal pregnant women. The results clearly showed that the detection of hCG protein in serum samples from pregnant women at 12-19 weeks could be used to screen Down's syndrome with high selectivity and sensitivity.

Conclusion: Our findings suggest the potential application of carboxyl-GO film in proof-of-concept studies for serum assays as a new type of SPR material. In addition, peptide and carboxyl-GO films may be conducive to the development of future point of care testing and rapid diagnostic devices for other diseases such as cancer.

Keywords: DS; Down’s syndrome; GO-COOH; SPR; aptasensor; carboxyl-functionalized graphene oxide; hCG; human chorionic gonadotropin; peptides; surface plasmon resonance.

MeSH terms

  • Adult
  • Aptamers, Peptide / chemistry
  • Biomarkers / blood
  • Buffers
  • Chorionic Gonadotropin / blood*
  • Down Syndrome / blood
  • Down Syndrome / diagnosis*
  • Female
  • Graphite / chemistry*
  • Humans
  • Limit of Detection
  • Peptides
  • Pregnancy
  • Prenatal Diagnosis / methods*
  • Sensitivity and Specificity
  • Spectroscopy, Fourier Transform Infrared
  • Surface Plasmon Resonance / instrumentation
  • Surface Plasmon Resonance / methods*

Substances

  • Aptamers, Peptide
  • Biomarkers
  • Buffers
  • Chorionic Gonadotropin
  • Peptides
  • graphene oxide
  • Graphite

Grants and funding

This study was supported by the Ministry of Science and Technology of the Republic of China (ROC), Taiwan, for financially supporting this research under Contract No. MOST 105-2221-E-003-027, MOST 106-2221-E-003-020, MOST 107-2221-E-003-009, MOST 108-2221-E-003 −020 -MY3, MOST 109-2221-E-003-028-MY3 and also Mackay Hospital (Project No. MMH-CT-10505).