A new and easy to construct sheathless capillary electrophoresis electro spray ionization mass spectrometry (CE-ESI-MS) interface was developed that offers several advantages compared to traditional liquid junction interfaces. The fabrication of the device only requires a CO2 laser engraver that most groups working with microfluids have access to. It only takes a few seconds to create a CO2 laser ablated opening in the bare-fused silica capillaries and the opening can be placed as close as a few mm from the spray tip. The capillary is punctured through a silicone tube such that the opening is directly placed inside this tube, which also serves as a liquid reservoir for the make-up liquid. Electrical contact required for both CE separation and ESI is established via the liquid in this reservoir which is in contact with the electrode of an external high voltage power supply. The developed CE-ESI-MS interface is capable of analysing both small molecules and biomolecules such as peptides in physisorbed PEG polymer brush coated capillaries. Proof-of-principle of the interface was demonstrated by analysing a tryptic digest of BSA. Further, a range of drugs of abuse were also investigated. The examined small molecules (pethidine, nortriptyline, methadone, haloperidol and loperamide) have a quantification limit (LOQ) of 150 ng/mL and a detection limit (LOD) of 40 ng/mL (except for loperamide: LOD = 80 ng/mL). Finally, we used our novel CE-MS interface for the analysis of the Aβ40 peptide. This is a member of the beta-Amyloid peptide family, involved in the development of Alzheimer's disease. A LOQ of 9 μg/mL was obtained for Aβ40, corresponding to 23 fmoles in a sample volume of 11 nL.