Lysophosphatidic acid (LPA) is present during the medical condition of ovarian cancer at all stages of the disease, and, therefore possesses considerable potential as a biomarker for screening its presence in female patients. Unfortunately, there is currently no clinically employable assay for this biomarker. In the present work, we introduce a test based on the duel protein system of actin and gelsolin that could allow the quantitative measurement of LPA in serum samples in a biosensing format. In order to evaluate this possibility, actin protein was dye-modified and complexed with gelsolin protein, followed by surface deposition onto silica nanoparticles. This solid-phase system was exposed to serum samples containing various concentrations of LPA and analyzed by fluorescence microscopy. Measurements conducted for the LPA-containing serum samples were higher after exposure to the developed test than samples without LPA. Early results suggest a limit of detection of 5 µM LPA in serum. The eventual goal is to employ the chemistry described here in a biosensor configuration for the large population-scale, rapid screening of women for the potential occurrence of ovarian cancer. these elevated levels indicate that LPA is a very promising marker for the early-stage detection of ovarian cancer.Commonly, LPA is detected and quantified in samples using standard analytical methods. This includes the use of capillary electrophoresis and ultraviolet detection [17,18], gas chromatography paired with flame atomic absorption spectroscopy or mass spectrometry [13,[19][20][21], thin-layer chromatography paired with mass spectrometry [15,[22][23][24][25], liquid chromatography paired with mass spectrometry [14,[26][27][28][29][30] or absorbance spectroscopy [31] and matrix-assisted laser desorption/ionization mass spectrometry [32][33][34]. Although these techniques are very sensitive towards LPA, they almost always require lipid extraction or other work-up of the serum samples before use. They also are highly labor intensive, time consuming, and use highly sophisticated instrumentation to quantify the marker. As such, these technologies are inappropriate for practical clinical analysis and, therefore, new methods that use simpler protocols and that are rapid and easy to perform in serum are required for an LPA assay to be included in a large-scale screening protocol for ovarian cancer.The protein gelsolin [35], which binds to LPA through a small chain of amino acids known as the PIP 2 -binding domain, is eminently capable of acting as a selective probe for the marker [36]. Gelsolin binds LPA with a high affinity measured by its K d of 6 nM [35,37]. The PIP 2 -binding domain, however, only binds LPA with a K d of 920 nM, suggesting that the interactions of LPA and gelsolin are heavily dependent on other components of the protein. The molecule itself is a large six-domain protein, with a molecular mass over 80 kDa [35]. Of the six domains, the protein essentially exists as two identical components comprised of domains 1-3 and dom...