Low-cost and rapid-production microfluidic sensors for cancer diagnosis anywhere by anyone
Ricardo A. G. de Oliveira,†,# Caroline Y. N. Nicoliche,†,# Anielli M. Pasqualeti,†,# Flavio M. Shimizu,†,# Iris R. Ribeiro,†,‡ Matias E. Melendez,§ André L. Carvalho,§ Angelo L. Gobbi,† Ronaldo C. Faria,|| and Renato S. Lima*,†,‡
† Laboratório Nacional de Nanotecnologia, Centro Nacional de Pesquisa em Energia e Materiais, Campinas, São Paulo 13083-970, Brasil
‡ Instituto de Química, Universidade Estadual de Campinas, Campinas, São Paulo 13083-970, Brasil
§ Centro de Pesquisa em Oncologia Molecular, Hospital de Câncer de Barretos, Barretos, São Paulo 14784-400, Brasil
|| Departamento de Química, Universidade Federal de São Carlos, São Carlos, São Paulo 13565-905, Brasil
ABSTRACT: This technical note describes a new microfluidic sensor that combines low-cost (US$0.97) with rapid fabrication and user-friendly, fast, sensitive, and accurate quantification of breast cancer biomarker. The electrodes consisted of cost-effective bare stainless-steel capillaries, whose mass-production is already well-established. These capillaries were used as received, without any surface modification. Microfluidic chips containing electrical double-layer capillary capacitors (μEDLC) were obtained by a cleanroom-free prototyping that allows the fabrication of dozens to hundreds of chips in 1 h. This sensor provided the successful quantification of CA 15-3, a biomarker protein for breast cancer, in serum samples from cancer patients. Antibody-anchored magnetic beads were utilized for immunocapture of the marker and, then water was added to dilute the protein. Next, the CA 15-3 detection (< 2 min) was made without using redox probes, antibody on electrode (sandwich immunoassay), or signal amplification strategies. In addition, the capacitance tests eliminated external pumping systems and precise volumetric sampling steps, as well as presented low sample volume (5 µL) and high sensitivity using bare capillaries in a new design for double-layer capacitors. The achieved limit-of-detection (92.0 µU mL–1) is lower than the most methods reported in the literature for CA 15-3, which are based on nanostructured electrodes. The data shown in this technical note support the potential of the µEDLC towards breast cancer diagnosis even at early stages. We believe that accurate analyses using a simple sample pretreatment such as magnetic field-assisted immunocapture and cost-effective bare electrodes can be extended to quantify other cancer biomarkers and even biomolecules by changing the biorecognition element.
This article was featured on cover of Analytical Chemistry (American Chemical Society,DOI: 10.1021/acs.analchem.8b02605). Such project has been conducted in Microfabrication Laboratory(Laboratório de Microfabricação, LMF, LNNano) in collaboration with UFSCar and Barretos Cancer Hospital.