Controlled liquid injection system in a continuous flow using MUX valves

In this application note, research engineer Hassan El Itawi and analytical chemist Cédric Guerin describe how to  setup a microfluidics-based controlled liquid injection system using the MUX distribution and the MUX recirculation valve.

The protocol allows the manipulation of up to 12 different samples in an automated microfluidic sequential injection fashion using the distribution valve. The recirculation valve allows the user to introduce microfluidic injection switches between two set-up configurations.

Liquid injection system and microfluidics

Microfluidic experiments may be used to optimise industrial-scale chemical processes like downstream processing, extraction, mixing and separation techniques. Contrary to pilot-scale experiments where litres of samples are consumed in relatively time-consuming manipulations that may take up to few days, microfluidic experiments give access to the intended information using few microliters of samples and shorter period. However, a precise liquid injection system of few microliters and their manipulation is a challenge of microfluidic experiments and requires the implementation of specific flow distribution instruments like (1) the MUX distribution valve (dist) and (2) the MUX recirculation valve (recirc) from Elveflow.

The distribution valve is a 12/1 rotatory selector bi-directional valve allowing to perform microfluidic automated sequential injection of up to 12 different samples. The recirculation valve is a 6-port /2 position valve allowing to perform microfluidic injection switches between two set-up configurations.

The present note highlights the precision of both instruments for controlled liquid injection through two different microfluidic experimental setups.

Applications

• Downstream processing
• Separation techniques
• Extraction
• Mixing

Materials

Experiment setup for a controlled liquid injection system

The experiments consist of injecting a chemical compound in a volume (V_s) of either 0.83 or 8.3 µL in a continuous flow of water. The fluids were degassed before the experiments. Figure 1 shows the scheme of the installation.

The OB1 pressure regulator was used to push both fluids (the sample and the water) from the pressurized reservoirs into the channels of the flow distribution instrument. The two flow distribution instruments dist and recirc were used to switch between the liquids.

The MFS2 flow sensor was connected to the outlet of the flow distribution instrument and the flow rate was set at 5 µL/min using a PID. The outlet of the flow sensor was connected to a detector, a high-resolution mass spectrometer (HRMS) that permits the real-time characterization of the flow. The dead volume that corresponds to the tubing connections between the distribution instrument and the HRMS detector is estimated at 180 µL (36 min at 5 µL/min flow rate).

Setting up liquid injection system using MUX distribution (dist) valve

The flow rate was set at 5 µL/min while the dist was set at the position permitting the injection of water (position 11 of figure 2). Once the flow rate is stable, the recording of the HRMS detector signal is turned on and the automatic sequence functionality of the ESI software was used to perform the following steps (Figure 2):

1. Keep dist at the position 11 to allow the circulation of water for 1 hour.
2. Switch the position of dist to 10 to permit the injection of the sample during 100 s for V_s = 8.33 µL or during 10 s for V_s = 0.83 µL.
3. Switch dist to the position permitting the circulation of water and keep it for 7 hours. The experiment may be stopped before 7 hours if the signal was stable.

Setting up liquid injection system using MUX recirculation (recirc) valve

First, a slice of tubing corresponding to the sample volume to be injected is cut (for V_s = 8.33 µL: PTFE tubing, ID = 0.794 mm, L= 167 mm; for V_s = 0.833 µL, PEEK tubing, ID = 0.2 mm, L = 264 mm).

Next, the channels of circ were connected according to mode A (load) shown in figure 3. The flow rate was set at 5 µL/min while recirc is always set at mode A (figure 3) to fill the sample loop and to circulate water through the HRMS detector. Once the flow rate is stable, the recording of the HRMS detector signal is turned on and the automatic sequence functionality of the ESI software was used to perform the following steps:

1. Keep recirc at the mode A for 1 hour.
2. Switch to mode B (Inject) and keep it for 7 hours. The sample in the loop will be pushed by the deionized water towards the HRMS detector (figure 3 mode B). The experiment may be stopped before if the signal was stable.

Experimental parameters

The flow rate was fixed at 5 µL/min in all experiments, and the two distribution instruments (i) dist and (ii) recirc were used to inject two sample volumes: (1) 8.33 µL and (2) 0.83 µL. Table 1 summarizes the experimental parameters.

Table 1: The parameters of the four different experiments.

Results

Figure 4 compares the curve of the HRMS detector signal of the experiments E1 (dist) and E2 (recirc) where V_s = 8.33 µL, and figure 5 shows the same information for E3 (dist) and E4 (recirc) where V_s = 0.83 µL. A significant peak is observed in all the experiments indicating that the sample was successfully injected and detected for both distribution instruments and both sample volumes. The apex of the peak is at 96.5 min for E1, 98.5 min for E2, 96.3 min for E3, and 95.9 for E4. The delay between the sample injection (at t= 60 min) and the peak corresponds to the estimated dead volume before the detector (180 µL).

Precise liquid injection system scales up processes

Microfluidics experiments can be used to efficiently optimize industrial scale processes like mixing and extraction processes using µL volumes of samples. Therefore, the precise control of the volume injection is of a significant importance.

Both MUX distribution valve and MUX recirculation valves can control and detect the injection of a samples with volumes less than 1 µl in a flow of 180 µL at relatively low flow rate (5µL/min), and the signals for both equipment were very similar.

For this type of applications, the MUX distribution valve has the advantage of the sequential injection of up to 12 samples on the MUX recirculation and no need to cut a piece of tubing each time the sample volume changes.