*2.1.1 Open coupling*

In the open-coupling system, the chromatographic column is connected to the MS with a T-shaped tube encompassing a smaller diameter tube (**Figure 2**). A deactivated fused silica or platinıumcapillary also leads to this tube and goes into the source of the MS. In order to evade condensation, the capillary needs to be kept under a vacuum and heated. The pressure inside the T-shaped tube must be equal to the atmospheric pressure, so the tube is closed at the edges but not sealed. The oxygen can oxidize the eluted molecules; in order to avoid that, helium is used. The diameter of the tube that enters the MS is essential. It needs to supply an adequate flow with regards to the gaseous conductance and pumping capacity. Hence the diameter of the capillary is 0.15 mm, and the length is 50 cm heated to 250°C will carry 2.5 ml/min of the eluted gas into the source. In practice, this is enough to pump everything coming out of a capillary column. The eluted molecules are not enhanced in an open-coupling system. The experiment is carried under the typical chromatographic environments, with one end of the column is under atmospheric pressure. The advantages of this system are the easiness of the column changing and the simplicity of the settings (no unique settings are needed). This system is generally used when no enhancement is required.

## *2.1.2 Direct coupling*

In this system, the capillary column enters the spectrometer source directly through a set of vacuum-sealed connections. No pumping is needed since the capillary is essentially very lengthy. The column inside diameter of 0.25 mm with a length of 15 m minimum is needed (**Figure 3**). The major downside of this system is not permitting the solvent's removal, and the column change is complex. When the column is sufficiently long, the chromatography is conducted between an atmospheric and vacuum at the opening and the other end of the column, respectively.
