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Abstract: In this contribution we present the first example of a microfluidic chip based on BaF2 for Infrared Microspectroscopy (IRMS) of living cells. The advantage in using barium fluoride as platform relies on its high IR transparency, especially in the spectral region below 1300cm−1, where the absorption bands of nucleic acids and carbohydrates are located. Barium fluoride is slightly soluble in water (0.12g/100g water) and it is potentially harmful for living cells. To overcome these problems, here we exploit an approach whose feasibility has been demonstrated previously on CaF2: the surface modification obtained by sputtering a thin Si layer on the surface. The Surface Modified Microfluidic Devices (SM-MD) hence obtained not only solve the BaF2 drawbacks, but also provide a silicon-like substrate fully compatible with standard micro-fabrication processes. These potentialities are here further explored in the direction of chemical or topographical nano-patterning of the silicon-like surface. The silicon thin layer was structured in the shape of 300nm wide grooves (500nm pitch) with a thickness of 35nm by using standard NIL and etching processes; chemical patterning was achieved by exploiting silane chemistry. Finally, we tested the performances of these devices at SISSI beamline@Elettra, collecting IR spectra of single MDA-MB-231 living cells maintained either in physiological solution or complete medium. A comparison of the spectra of a single cell obtained in BaF2 and CaF2 MDs is reported. [Copyright &y& Elsevier]