Highly sensitive detection of multiple tumor markers for lung cancer using gold nanoparticle probes and microarrays

- A co-detection method based on gold nanoparticles and microarrays is reported for detecting multiple biomarkers.
- A gold nanoparticle/antibody composite is synthesized as detecting probe.
- The gold deposition staining with HAuCl4 and H2O2 produces a color change that can be observed with the naked eye.
- This protein biochip is capable of detecting multiple biomarkers in 12 serum samples simultaneously in 1 h.
- The results confirm the clinical significance of DKK1 as a serologic marker of lung cancer.

Assay of multiple serum tumor markers such as carcinoembryonic antigen (CEA), cytokeratin 19 fragment antigen (CYFRA21-1), and neuron specific enolase (NSE), is important for the early diagnosis of lung cancer. Dickkopf-1 (DKK1), a novel serological and histochemical biomarker, was recently reported to be preferentially expressed in lung cancer. Four target proteins were sandwiched by capture antibodies attached to microarrays and detection antibodies carried on modified gold nanoparticles. Optical signals generated by the sandwich structures were amplified by gold deposition with HAuCl4 and H2O2, and were observable by microscopy or the naked eye. The four tumor markers were subsequently measured in 106 lung cancer patients and 42 healthy persons. The assay was capable of detecting multiple biomarkers in serum sample at concentration of <1 ng mL−1 in 1 h. Combined detection of the four tumor markers highly improved the sensitivity (to 87.74%) for diagnosis of lung cancer compared with sensitivity of single markers. A rapid, highly sensitive co-detection method for multiple biomarkers based on gold nanoparticles and microarrays was developed. In clinical use, it would be expected to improve the early diagnosis of lung cancer.

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