Stealth modified bottom up SERS substrates for label-free therapeutic drug monitoring of doxorubicin in blood serum

Herein, we report the simple and inexpensive approach for the large-scale fabrication of uniform bottom-up Surface Enhanced Raman Spectroscopy (SERS) substrate. SERS substrate was fabricated by controlled sputtering of 10 nm thick gold film on self-assembled silica nanoparticles (SiNPs) of similar to 120 nm on glass substrates. The SERS detection has been firstly demonstrated using Rhodamine B as a Raman probe molecule with a detection limit of 10-10 M on Au sputtered SiNPs (i.e., Au@SiNPs). The experimental Raman enhancement from 0 to 6 was achieved on Au@SiNPs due to the generation of multiple SERS hotspot. To combat blood serum fouling, the zwitterionic modification of L-cysteine was done on Au@SiNPs substrates which lowered blood serum fouling by 48%. Our SERS-based sensor demonstrated high reproducibility for the detection of Doxorubicin in undiluted blood serum with a limit of detection of 20 nM, which greatly exceeded the detection range of available methodologies. We envision that the translation of this SERS substrate for the detection of chemo-drugs like Doxorubicin will assist clinicians in making rapid and/or early decisions in patients undergoing sustained chemotherapy to lower its side-effects or to incorporate other treatment methodologies as an option for Personalized treatment.