Cancer Biomarker Methylmalonic Acid Detection by Molecularly Imprinted Polyaniline Paper Sensor †

Methylmalonic acid (MMA) plays a vital role in metabolism and energy production. It has been studied and reported as a sensitive early indicator for mild or serious Vitamin B12 deficiency. The normal range in health people is from 0.00 to 0.40 µM. Thus, most of MMA detection research was focused on Vitamin B12 deficiency with a small detection range. Recently, MMA has been reported to promote tumor progression due to age-induced accumulation. It was found that MMA concentration can reach as high as 80 µM in elderly people. MMA can be of great value as a promising biomarker for cancer diagnostics, as well as a therapeutic target for cancer treatment. Clinical determination of MMA concentration is by the method of gas chromatography mass spectroscopy (GCMS) or liquid chromatography mass spectroscopy (LCMS). However, these methods require extensive sample pre-treatment and large sample volume. They are also expensive and time-consuming. Hence, we proposed an attractive and effective strategy to detect MMA with a broad linear range by a low-cost molecularly imprinted polyaniline paper sensor. The polyaniline paper strip was fabricated by a one-step solution process using MMA as the template by molecular imprinting technology. The concentration of MMA was determined by the resistance change of the paper sensor. A calibration curve as a function of MMA concentration in aqueous solution was acquired with a correlation coefficient of 0.962. We demonstrated detection of the added MMA in plasma with a wide concentration range of 0 to 100 µM with a limit of detection (LoD) of 0.197 µM. This low-cost disposable paper sensor shows great potential in point-of-care MMA detection for cancer prognostics and diagnostics, especially in underserved communities.