Towards malaria field diagnosis based on surface-enhanced Raman scattering with on-chip sample preparation and near-analyte nanoparticle synthesis (September, 2021))

We report a chip based on surface-enhanced Raman scattering (SERS) developed towards malaria field diagnosis. Only a mixture of 10-μl water and 10-μl blood is required as the sample input to the chip. Water is the only lysing agent to hemolyze blood cells while keeping the malaria biomarkers, hemozoin biocrystals, at locally high concentrations within parasites and/or their vacuoles. Then, SERS-active silver nanoparticles are synthesized on site near hemozoin in these concentrated regions when the blood/water mixture flows through and dissolves dried chemical patches that are earlier deposited inside the channel, which subsequently arrives at the detection region for SERS measurements. It should be highlighted that the procedure can be accomplished without a laboratory requirement and the risk of exposure to hazardous chemicals. Additionally, raw chemicals deposited inside the chip are chemically more stable than those readymade SERS substrates, thus the shelf life of the chip can be much longer. Furthermore, the chip yields analytical enhancement factor values ranging from 5.4 × 103 to 1.9 × 106 that are comparable to other ready-made SERS substrates in the literature. This strategy is capable of quantifying hemozoin concentrations in malaria infected human blood with a root-mean-square error of prediction of 0.3 μM, and a detection limit of 0.0025 % parasitemia level for parasites in the ring stage (equivalent to 125 parasites/μl) with a room of extra enhancement by switching the laser to a more suitable wavelength. These results show the feasibility to exploit this cost-effective yet highly sensitive SERS-based technique for malaria field diagnosis.