Do we really need sub-micron resolution to analyse single cell molecular features through vibrational spectroscopy? A pilot study using Plasmodium falciparum-infected Human Erythrocytes

Abstract Malaria is one of the major life-threatening diseases to afflict humanity with an estimated 228 million cases worldwide in 2018. There exists no approved Malaria vaccine on the market yet, partly due to the complexity of the parasite life cycle and the vast repertoire of polymorphic proteins they express during different stages of development. In this work, we have tested two emerging spectroscopic approaches: Optical Photothermal Infrared (O-PTIR) spectroscopy and Atomic Force Microscopy combined with infrared spectroscopy (AFM-IR) in contrast to the more traditional Fourier Transform InfraRed (FTIR) microspectroscopy which has emerged recently as a new promising tool to provide label-free analysis of cell and tissue sections. Examples of chemical spatial distributions of selected bands and spectra for Plasmodium falciparum infected RBCs collected with the three modalities are presented and compared together with advantages and limitations of each method. Based on these results, it appears that O-PTIR and AFM-IR techniques can be explored as powerful tools for the analysis of cells and ipso facto, these methods can help in better understanding complex processes occurring within heterogeneous objects such as infected RBC due to their superior spatial resolution in comparison with traditional approaches for infrared spectroscopic characterization.