The gold standard method for detecting nucleic acid markers is the polymerase chain reaction. However, this method demands high technical skills, labor-intensive, time-consuming, and expensive. Many resource-limited countries around the globe do not have access to such laboratory-based PCR tests. To address the global test needs of virus and other pathogen infections, as well as address the early biomarker detection of diseases. We have developed an affordable nanoparticle colorimetric sensor approach. In our system, the virus RNA marker is captured by the complementary oligonucleotide attached to low fouling gold-coated iron oxide nanoparticles. Further specificity is achieved through a second complementary hybridization probe conjugated with streptavidin-horseradish peroxidase labels. Visual colorimetry is performed using a chromogenic substrate allowing the visual conversion of the colorless solution to a blue color confirming a positive test. The intensity of the color is in direct correlation to the concentration of the virus RNA marker. We have successfully demonstrated attomolar detection in buffer and picomolar detection in real undiluted biofluids such as in neat human serum. Our ongoing efforts focus on saliva-based non-invasive detection with ultra-low capabilities, optimization of the assay, repeatability, and expanding this work for a multiplex detection format