title: Multiplexed detection of serological cancer markers with plasmon-enhanced Raman spectro-immunoassay.
abstract: Circulating biomarkers have emerged as promising non-invasive, real-time surrogates for cancer diagnosis, prognostication and monitoring of therapeutic response. Emerging data, however, suggest that single markers are inadequate in describing complex pathologic transformations. Architecting assays capable of parallel measurements of multiple biomarkers can help achieve the desired clinical sensitivity and specificity while conserving patient specimen and reducing turn-around time. Here we describe a plasmon-enhanced Raman spectroscopic assay featuring nanostructured biomolecular probes and spectroscopic imaging for multiplexed detection of disseminated breast cancer markers cancer antigen (CA) 15-3, CA 27-29 and cancer embryonic antigen (CEA). In the developed SERS assay, both the assay chip and surface-enhanced Raman spectroscopy (SERS) tags are functionalized with monoclonal antibodies against CA15-3, CA27-29 and CEA, respectively. Sequential addition of biomarkers and functionalized SERS tags onto the functionalized assay chip enable the specific recognition of these biomarkers through the antibody-antigen interactions, leading to a sandwich spectro-immunoassay. In addition to offering extensive multiplexing capability, our method provides higher sensitivity than conventional immunoassays and demonstrates exquisite specificity owing to selective formation of conjugated complexes and fingerprint spectra of the Raman reporter. We envision that clinical translation of this assay may further enable asymptomatic surveillance of cancer survivors and speedy assessment of treatment benefit through a simple blood test.
authors.affiliation: Department of Mechanical Engineering, Johns Hopkins University, Baltimore, Maryland 21218, United States ; Laser Biomedical Research Center, George R. Harrison Spectroscopy Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Laser Biomedical Research Center, George R. Harrison Spectroscopy Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
authors.forename: Jeon Woong
authors.initials: JW
authors.lastname: Kang
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, United States.
authors.forename: Saraswati
authors.initials: S
authors.lastname: Sukumar
authors.affiliation: Laser Biomedical Research Center, George R. Harrison Spectroscopy Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
authors.forename: Ramachandra Rao
authors.initials: RR
authors.lastname: Dasari
authors.affiliation: Department of Mechanical Engineering, Johns Hopkins University, Baltimore, Maryland 21218, United States ; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, United States.
authors.forename: Ishan
authors.initials: I
authors.lastname: Barman