High throughput continuous titration based on a flow ratiometry controlled with feedback-based variable triangular waves and subsequent fixed triangular waves

We propose a new approach for high-throughput continuous titration based on a flow ratiometry. The method was applied to potentiometric titrations of acids and bases. A base solution, the flow rate F_B of which was varied in response to controller output voltage V_c, was merged with an acid solution under constant total (acid + base) flow rate. Downstream, the pH of the mixed solution was measured with a flow-through glass electrode. Initially, V_c, and thus F_B was increased linearly. At the instant the equivalence point (EP) was sensed, the ramp direction of V_c was reversed from upward to downward. The direction was reversed to upward when EP was sensed again. Such the feedback-based operation gives a triangular waveform of V_c, because there is a delay corresponding mainly to the transit time of merged solutions to reach the sensor. The value of V_c that gives EP composition, V_E, was estimated by averaging the most recent maximum and minimum values of V_c. Next, fixed triangular waves of V_c was used to control F_B. The amplitude and the scan rate of the waves were fixed narrower and faster, respectively, than those in the feedback-based operation in order to improve the throughput rate. The EP can be located as long as the scan range covers V_E. These automated processes limited the titration to just the narrow range around EP, and thus realized extremely high throughput rate of maximally 17.6 titrations per minute (=3.4 s per titration) at R.S.D. = 0.35%.