Cu₂S/Hβcd-rGO: Ultrasensitive Sensor Composite

• The paper reports a novel Cu₂S/Hβcd-rGO composite that integrates copper sulfide nanocrystals with cyclodextrin-functionalized rGO, achieving ultrasensitive serotonin detection with a LOD of 1.2 nM.
• The methodology involves a multi-step synthesis including hydrothermal nanoparticle formation, rGO reduction, and Hβcd functionalization, followed by extensive structural and electrochemical characterization.
• The composite demonstrates enhanced charge transfer (Rct = 61 Ω), selectivity against interferents, and >95% activity retention over 15 days, positioning it as a promising electrocatalyst for neurotransmitter sensing.

Copper sulfide-hydroxypropyl-β-cyclodextrin-reduced graphene oxide (Cu₂S/Hβcd-rGO) is a hybrid nanocomposite engineering electrocatalyst featuring the integration of copper sulfide nanocrystals, hydroxypropyl-β-cyclodextrin (Hβcd)-functionalized reduced graphene oxide (rGO), and efficient molecular recognition sites for electrochemical sensing. Developed for ultrasensitive serotonin (5-hydroxytryptamine, SR) detection, this platform achieves enhanced catalytic activity, superior charge transfer, and anti-fouling selectivity in biologically relevant environments (Santhan et al., 6 Nov 2025).

1. Synthetic Workflow and Composite Architecture

The Cu₂S/Hβcd-rGO composite synthesis involves distinct sequential steps:

• Copper Sulfide (Cu₂S) Nanoparticle Synthesis: A hydrothermal process combines CuSO₄·5H₂O (0.1 M) with oxalic acid in deionized water, followed by reaction with Na₂S₂ at 140 °C for 14 h in an autoclave. Subsequent centrifugation (5000 rpm, 15 min) with water/ethanol washes removes impurities. The intermediate is dried (60 °C) and annealed at 500 °C for 5 h, yielding Cu₂S nanocrystals. The key reaction is Cu²⁺ + S²⁻ → Cu₂S ↓.
• Reduced Graphene Oxide (rGO) Production: Graphene oxide is reduced with ascorbic acid at 90 °C for 12 h, followed by centrifugation and drying.
• Hβcd Functionalization of rGO: rGO and Hβcd are mixed (100 mg rGO:200 mg Hβcd) in 50 mL water/25 mL ethanol, ultrasonicated 1 h, stirred 12 h, washed, and dried, yielding Hβcd-rGO. Octadecylamine modification is performed as a comparison.
• Composite Assembly: Cu₂S (200 mg) and Hβcd-rGO (100 mg) are dispersed in 75 mL mixed solvent, ultrasonicated 1 h, stirred for 12 h, washed/centrifuged, and dried to yield the final hybrid.

Integration relies on van der Waals attraction between Cu₂S and graphene surfaces, plus electrostatic and hydrogen bonding between Hβcd’s hydroxyl groups and the nanoparticle surface. Aggregation is minimized compared to pure Cu₂S/Hβcd, ensuring homogeneous dispersion and improved conductivity.

2. Structural and Physicochemical Characterization

Multiple analytical methodologies confirm the composite’s structure, composition, and interfacial coupling:

• X-Ray Diffraction (XRD): Cu₂S displays tetragonal crystallinity (P4₃2₁2, a = b = 3.996 Å, c = 11.287 Å). Main peaks: (101) @ 23.5°, (102) @ 27.6°, (215) @ 67.1°. Hβcd-rGO shows (002) @ 25.8°, (100) @ 42.6°. The composite presents broadened peaks, indicative of reduced grain size and increased disorder: D(Cu₂S) = 68.4 nm, D(Hβcd-rGO) = 8.2 nm, D(Cu₂S/Hβcd-rGO) = 32.4 nm per Scherrer’s equation.
• FT-IR: Cu₂S reveals bands from S–S (520 cm⁻¹), Cu–S (608 cm⁻¹); Hβcd-rGO’s spectrum retains glycosidic and C–O–C features at 1155 cm⁻¹ and 1030 cm⁻¹, respectively. The composite overlays spectral fingerprints of both components.
• Raman Spectroscopy: Cu₂S shows A₁g (484 cm⁻¹) and Cu–S (267 cm⁻¹) modes. rGO derivatives show the D (∼1340 cm⁻¹) and G (∼1570 cm⁻¹) bands. The ID/IG ratio, reflecting defect density and sp²/sp³ hybridization, increases with functionalization (e.g., ODA-rGO: 1.13; Hβcd-rGO: 1.01).
• Electron Microscopy (SEM/TEM): SEM shows Cu₂S platelets uniformly decorating wrinkled rGO sheets in the Hβcd-coupled composite. TEM and SAED highlight lattice fringes (d = 0.097 nm and 0.084 nm for (112) and (113) planes), confirming phase mixing and intimate interface.
• XPS: Core-level spectra: Cu 2p₃/₂ @ 932.5 eV, S 2p₃/₂ @ 161.1 eV, C 1s (C–C @ 284.4 eV, C=C @ 285.9 eV, C–O @ 287.3 eV). Additional C–O or O–C=O on functionalized rGO, and N 1s @ 400 eV for amide/amine in ODA-rGO. Binding energy shifts reflect electronic coupling at the Cu₂S/Hβcd-rGO interface.

3. Electrochemical Interface, Kinetics, and Mechanism

• Electrode Fabrication: Glassy carbon electrode (GCE) is polished, rinsed, and drop-cast with 6 μL of 3 mg/mL Cu₂S/Hβcd-rGO dispersion, then dried at 60 °C.
• Charge Transfer Resistance (Rct): Nyquist analysis in [Fe(CN)₆]³⁻/⁴⁻ (0.1 M KCl, 1 Hz–1 MHz) reveals Rct decreasing in the following sequence: bare GCE (497 Ω), Cu₂S/GCE (410 Ω), rGO (333 Ω), Hβcd-rGO (266 Ω), Cu₂S/rGO (150 Ω), Cu₂S/Hβcd-rGO (61 Ω). The Cu₂S/Hβcd-rGO shows the lowest Rct, consistent with maximum charge-transfer facilitation.
• Serotonin Oxidation: At pH 7, the composite catalyzes a two-electron/two-proton oxidation:

$\ce{Serotonin + 2H2O ->[Cu2S/HBcd-rGO] Quinoneimine + 2e^- + 2H^+ }$

The oxidation peak appears at ~0.36 V vs. Ag/AgCl.

• Cyclic Voltammetry (Randles–Ševčík):

$$i_p = (2.69 \times 10^5) n^{3/2} A D^{1/2} C v^{1/2}$$

$n = 2$, $A =$ geometric area, $D =$ diffusion coefficient, $C =$ concentration, $v =$ scan rate.

• Scan-Rate and pH Dependence: The peak current varies linearly with scan rate ($i_p \propto v$, $R^2 = 0.9922$), indicating adsorption-controlled behavior. Peak potential shifts −60 mV/pH (pH 3–11, $R^2 = 0.9817$), confirming a two-proton, two-electron process.
• DPV Calibration: DPV (step 5 mV, pulse 50 mV) shows two linear dynamic ranges for serotonin:
  • $$i_p = (2.69 \times 10^5) n^{3/2} A D^{1/2} C v^{1/2}$$0M: $$i_p = (2.69 \times 10^5) n^{3/2} A D^{1/2} C v^{1/2}$$1 ($$i_p = (2.69 \times 10^5) n^{3/2} A D^{1/2} C v^{1/2}$$2)
  • $$i_p = (2.69 \times 10^5) n^{3/2} A D^{1/2} C v^{1/2}$$3M: $$i_p = (2.69 \times 10^5) n^{3/2} A D^{1/2} C v^{1/2}$$4 ($$i_p = (2.69 \times 10^5) n^{3/2} A D^{1/2} C v^{1/2}$$5)

4. Analytical Performance and Practical Validation

The composite demonstrates the following sensor characteristics:

Metric	Value	Reference
Sensitivity	15.9 μA μM⁻¹ cm⁻² (low-range, area-normalized)	(Santhan et al., 6 Nov 2025)
LOD	1.2 nM (3σ/m)	(Santhan et al., 6 Nov 2025)
Linear ranges	0.019–0.299 μM; 4.28–403.14 μM	(Santhan et al., 6 Nov 2025)
Rct (EIS)	61 Ω (Cu₂S/Hβcd-rGO/GCE)	(Santhan et al., 6 Nov 2025)
Selectivity	Negligible SR peak impact from interferents	(Santhan et al., 6 Nov 2025)
Stability	>95% activity retained after 15 days	(Santhan et al., 6 Nov 2025)
Real sample rec.	98.7–99.8% (human serum, n=3, RSD<2%)	(Santhan et al., 6 Nov 2025)

Performance is benchmarked against other nanostructured electrocatalysts (e.g., FeVO₄/Ti₃C₂ MXene: LOD 5.88 nM; Zn₂P₂O₇/NbC: 5.5 nM), wherein Cu₂S/Hβcd-rGO exhibits among the lowest reported LOD for SR.

Selectivity is affirmed by negligible response changes in the presence of 4-aminophenol, dopamine, epinephrine, hydroquinone, melatonin, Cl⁻, Hg²⁺, and 4-nitrophenol. Repeatability (five CVs, RSD<4%) and 15-day shelf stability support robust operational use.

5. Comparative Perspective, Strengths, and Limitations

Cu₂S/Hβcd-rGO’s main advantages include:

• Rapid, scalable one-step assembly (ultrasonication + drying)
• Low-cost constituent materials (Cu₂S, cyclodextrin)
• Superior sensitivity (15.9 μA μM⁻¹ cm⁻²) and LOD (1.2 nM)
• High selectivity and real-sample compatibility
• Durable electrocatalytic activity over 15 days

Key limitations are:

• Two-segment calibration complicates dynamic range analysis.
• Ethanol use in synthesis may reduce environmental sustainability.

6. Extended Applications and Functional Scope

Beyond serotonin quantification in serum, broader prospective applications include:

• Electroanalysis of other neurotransmitters (e.g., dopamine, melatonin) by cyclodextrin-mediated host–guest chemistry
• Detection of phenolic contaminants, heavy metal ions (Hg²⁺), and pharmacological analytes
• Integration into microfluidic or point-of-care sensor devices
• Use in photocatalytic/photothermal platforms (composite bandgap ≈ 0.80 eV), potentially enabling photoelectrochemical coupling

A plausible implication is that molecular recognition from the Hβcd units, in concert with the hierarchical nanoarchitecture and accelerative electron transfer, positions Cu₂S/Hβcd-rGO at the forefront of miniaturized, multiplexed electrochemical sensor development.

7. Summary

Cu₂S/Hβcd-rGO constitutes a robust, ultrasensitive, and selective platform for neurotransmitter detection. The composite’s distinctive synergy—high surface area, rapid charge transfer, and cyclodextrin-specific molecular recognition—delivers both technical and practical advances. Facile synthesis, exceptional analytical figures of merit, and versatility for real-sample diagnostics or environmental surveillance establish this hybrid as a prominent candidate in contemporary sensor research (Santhan et al., 6 Nov 2025).