Raman spectroscopy based assay for both low and high abundant biomolecules in a biological fluid sample

A method for assaying a biological fluid sample, comprising:

• placing a biological fluid sample in contact with a first nanostructure surface free of any biomolecule targeting agents;
• interrogating a biological fluid sample in contact with the first nanostructure surface with a light source, the interrogation using a surface enhanced Raman spectroscopic (SERS) technique configured to produce an enhanced Raman scattering from at least one type of high abundant biomolecule present within the biological fluid sample adsorbed on the first nanostructure surface;
• detecting the enhanced Raman scattering from the at least one type of high abundant biomolecule using a light detector configured to produce first signals representative of the enhanced Raman scattering from the at least one type of high abundant biomolecule;
• placing the biological fluid sample in contact with at least one second nanostructure surface, the at least one second nanostructure surface functionalized with at least one targeting agent configured to target at least one type of low abundant biomolecule;
• interrogating the biological fluid sample in contact with the at least one second nanostructure surface with the light source, the interrogation configured to produce Raman scattering from the at least one type of low abundant biomolecule captured by the at least one targeting agent functionalized on the at least one second nanostructure surface;
• detecting the Raman scattering from the at least one type of low abundant biomolecule and producing second signals representative thereof;
• assaying the biological fluid sample using the first signals and the second signals.

A system for assaying a biological fluid sample, comprising:

• a first nanostructure surface free of biomolecular targeting agents;
• at least one second nanostructure surface functionalized with at least one targeting agent configured to target at least one type of low abundant biomolecule within the biological fluid sample;
• a light source;
• a light detector;
• a system controller in communication with the light source, the light detector, and a memory storing instructions, which instructions when executed cause a processor to:
• control the light source to interrogate the biological fluid sample disposed in contact with the first nanostructure surface with a beam of light, wherein the interrogation is part of a surface enhanced Raman spectroscopic (SERS) technique configured to produce an enhanced Raman scattering from at least one type of high abundant biomolecule present within the biological fluid sample and adsorbed on the first nanostructure surface;
• control the light detector to detect the enhanced Raman scattering from the at least one type of high abundant biomolecule and produce first signals representative of the enhanced Raman scattering from the at least one type of high abundant biomolecule present within the biological fluid sample;
• control the light source to interrogate the biological fluid sample disposed in contact with the at least one second nanostructure surface with a beam of light, wherein the interrogation is part of a SERS technique configured to produce an enhanced Raman scattering from the at least one type of low abundant biomolecule within the biological fluid sample and captured by the at least one targeting agent functionalized on the at least one second nanostructure surface;
• control the light detector to detect the enhanced Raman scattering from the captured at least one type of low abundant biomolecule within the biological fluid sample and produce second signals representative thereof;
• assay the biological fluid sample using the first signals and the second signals.