A portable eight-channel titrator based on high-throughput capacitively coupled contactless conductivity measurements

Accepted Manuscript A portable eight-channel titrator based on high-throughput capacitively coupled contactless conductivity measurements Xuzhi Zhang, Qianqian Yang, Xiaoyu Jiang, Jun Zhao, Chuan Zhao, Keming Qu PII: DOI: Reference:

S0263-2241(18)31117-5 https://doi.org/10.1016/j.measurement.2018.11.063 MEASUR 6106

To appear in:

Measurement

Received Date: Revised Date: Accepted Date:

14 June 2018 24 October 2018 19 November 2018

Please cite this article as: X. Zhang, Q. Yang, X. Jiang, J. Zhao, C. Zhao, K. Qu, A portable eight-channel titrator based on high-throughput capacitively coupled contactless conductivity measurements, Measurement (2018), doi: https://doi.org/10.1016/j.measurement.2018.11.063

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A portable eight-channel titrator based on high-throughput capacitively coupled contactless conductivity measurements Xuzhi Zhanga,b, Qianqian Yangc, Xiaoyu Jiangc, Jun Zhaoa, Chuan Zhao d*, Keming Qua,b* a

Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China

b

Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National

Laboratory for Marine Science and Technology, Qingdao 266235, China c

College of Marine Sciences, Shanghai Ocean University, Shanghai 201306, P.R. China

d

School of Chemistry, University of New South Wales, Sydney, NSW 2052, Australia

Abstract Analytical chemists require multichannel and automatic tools for batch measurements. Herein, an eight-channel electronic titrator (8-CET) system was constructed to facilitate high-throughput titrations. In this system, multichannel piston pumps were used for delivery, and an 8-channel capacitively coupled contactless conductivity detector (8-C4D) was used to monitor the conductivity of the titration solutions in arrays of disposable reaction cells. The delivery and the monitoring were both fully software-controlled allowing a simultaneous formation of eight titration curves. Its capacity for classical acid-base and precipitation titration was characterized with satisfactory results. It was also used to measure the content of CH3COOH in batched vinegar samples. The RSD between each reaction cell was 1.9%. There are two outstanding features of this new system: 1) Up to eight samples can be measured simultaneously; and 2) simple operation is realized by avoiding electrode switching and cleaning after each measurement. Therefore, it is reasonable to believe that this 8-CET system is a prospective alternative for developing more automatic and efficient titration platforms. Keywords: electronic sensor; capacitively coupled contactless conductivity detector; automatic titrator; multichannel titration

Introduction Titrimetry - also known as volumetric analysis - has been in use for over a hundred years and is still popular especially for measuring major components in macro-scale samples, in virtue of its excellent 1 / 15

advantages regarding precision, convenience, affordability, etc [1-4]. It is the primary method for analysis and continues to be used for the validation of secondary methods [1,5]. The past decade has seen a growth in titrimetric technologies. On one hand, novel visual-based protocols for point-of-care use remain intriguing [6]. On the other hand, the development and application of automatic devices, which can result in higher sensitivity, accuracy and precision, are reported more frequently, for both laboratory analysis and point-of-care assays [2-4,7-12]. In both chemical laboratories and industrial process controls, there are usually many samples in a batch. For example, in marine environmental studies [13] or a drinking water quality inspection [14], the chemical oxygen demand (COD) in dozens (even hundreds) samples need to be determined by titration. Similarly, when testing the total volatile fatty acids in anaerobic digestion of energy crop, animal slurry, and/or food waste, there are often hundreds of samples at a time [11]. While dozens of samples can be digested simultaneously, the determination efficiency is difficult to be improved due to a lack of multichannel titrators - even with successful implementation of automatic titration methods. Thus, it is of interest to develop automatic titrators capable of measuring many samples simultaneously. Since the middle of last century, considerable efforts have been made in the development of automatic titrators. To identify endpoints/equivalence points, optical [4,9,15,16] and electrochemical [8,10-12,17-20] devices are most often used to monitor/record the titration. Generally, optical methods based on photometric or spectrophotometric instrumentations utilize a rapid color change at the titration endpoint [2].They have two outstanding advantages: 1) satisfactory accuracy and sensitivity [16]; and 2) risk-free contamination of head stage by components in the solution. However, they are confined because one or more special indicators are needed [4,15,16], and indicator errors can result from the difference between the endpoint and equivalence point [22]. There are also performance limits to transparent solutions and vessel. In contrast, electrochemical methods, which identify titration endpoints by monitoring the change of voltage [2,14,19,22] or conductivity [8,10,17,18,20], are easier to be miniaturized because they do not need sophisticated optical components or photo-electric conversion systems [8,15]. In particular, conductivity mode is interesting because the conductivity of a solution is well established and is very suitable for recording faster changes because the electrodes do not have to equilibrate [18]. In principle, it can be used for all the four routine type titrations, without involving any indicators [17]. However, there are two critical challenges to using classical electrochemical methods for monitoring titration that 2 / 15

result from the tip of the working electrode being immersed in the titration solution rather than a noninvasive test [20]. First, electrode deterioration is unavoidable and may result in erratic measurements that decrease the accuracy. Second, electrodes must be cleaned before each measurement to minimize the memory effect resulting from physical and/or chemical foiling [19,23]. Therefore, even if an array of titration units was fabricated, it is difficult to improve the performance due to these complicated operations. To resolve the problem faced by contact electrochemical methods, we have developed a capacitively coupled contactless conductivity detector (C4D) to monitor titration [23] and have validated its capacity for all four routine kinds of titrations, i.e. acid-base, precipitation, complexation, and redox titrations. In this strategy, a disposable glass reaction cell was used to load titrand. Upon addition of titrant, the ionic strength and/or mobility of components in the solution changed, causing a change in conductivity that was monitored by the C4D in real time to form a V-shaped titration curve. The endpoint was identified easily from the valley of the curve. This strategy is not only a versatile platform, but also offers instrumental simplicity, low cost, and rapid response. It is free from transparent solution requirements, and is easy to be miniaturized, just like other classical electrochemical methods. It is also free of polarization effects and passivation [23,25-27], like optical methods [26]. It is especially worth noting that the operation is very simple because it eliminates the renewal requirement for working electrodes and vessels. Satisfactory results were obtained when the strategy was applied to measure the content of CH3COOH in batched vinegar samples.

Experimental section Chemical materials Hydrochloric acid, acetic acid, sodium hydroxide, potassium chloride and other common chemicals were purchased from Shanghai Chemical Reagent Co. (Shanghai, China) and were of analytical grade. Batched vinegar samples were purchased in a local supermarket and analyzed without any further treatment except for dilution. Fresh titrands (HCl solutions) and titrants (NaOH solutions) were used for the acid-base titration [28]. Solutions were all prepared with ultrapure water (Resistivity: 18.2 MΩ cm−1) from Poseidon-R70 water purification system (Research Scientific Instruments Co. LTD, Xiamen, China). Structure and component parts of 8-CET system

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As shown in Fig. 1, the 8-CET system consists of three key functional modules. One module is for the automatic titrant delivery that is composed of control part, piston pump and syringe needle. Among the automatic delivery control system, input and display part -Weinview TK6070iP Touch screen – was produced by Shenzhen Weintech Co., Ltd. (Shenzhen, China); storage and operation part - a programmable logic controller (model: FX3U-32MT/ES) – was purchased from Mitsubishi Electric Co., Ltd. (Beijing, China); two 4-channel piston pumps (model: SP4-E1) was purchased from Longer Precision Pump Co., Ltd. (Baoding, China); electrical elevator mechanism (model: 1206-240) was produced by Linear Technology Co. (San Francisco, USA); 8-channel syringe needles array was homemade and silicone hose (ID = 0.8 mm) was purchased from local market. The second module is for the monitoring of titration reactions and is composed of a custom-made 8-channel C4D (ER815, eDAQ Pty Ltd., Sydney, Australia) and a portable computer. The third module is an array of automated stirring (300 r/min). For titration, an array of disposable glass tubes (OD = 5.0 mm, ID = 4.0 mm) were used as reaction cells. Some of the key components are shown in supplementary information (Fig. S1).

Portable computer

1 2

(B)

3 4 8-channel C4D 5 6

(C)

(A)

Fig. 1 (A) Illustration of the structure and principle of the 8-CET system; (B) Picture of the head stage of the custom-made 8-channel C4D; (C) Picture of the 8-CET system (excluding computer and the cables). 1- Automatic delivery control system; 2- Piston pumps array; 3- Syringe needles array; 4Reaction cells array; 5- Electrodes array; 6- Stirrings array. Characterization of delivery module and 8-channel C4D The delivery volume per pulse can be adjusted over the range of 5–15 μL; the interval time can be adjusted from 1s to 9999 s; and the delivery replicates can be adjusted over the range of 1–500. The accuracy, uniformity and precision of the delivery module were evaluated in quintuplicate at 5, 6, 7, 8, 4 / 15

9, 10 11 and 12 μL per pulse. Briefly, pure water was delivered simultaneously into eight reaction cells with set volumes per pulse for 10 times, respectively. Then the quality of water in each reaction cell was measured with an electronic balance (MS204TS/02, METTLER TOLEDO, Zurich, Switzerland) [18]. The custom-made 8-channel C4D has special run system and was fully software controlled. The first operation was an Auto Zero. To prepare the system for auto zero, 8 empty reaction cells were inserted into the 8-channel head stage followed by an incubation of 2 min to allow temperature stability. We then issued a “set channel all offset auto” command. The system then took 10 s for measuring, averaging and determining the zero offset on each channel. It then applied an offset adjustment to reduce the typical zero error to less than ± 0.001 V. The sensitivity and stability of the custom-made 8channel C4D were evaluated according to our previous method [26]. Briefly, the apparent conductivities (output in voltage) of solutions in 8 reaction cells were measured in quintuplicate, respectively, using 0.01, 0.02, 0.05, 0.10, 0.20 and 0.30 M KCl as probes. Meanwhile, the uniformity of conductivity response between each detector of the 8-channel C4D was also evaluated. Procedure of titration To evaluate the performance of multichannel titration, the operator first turned on the automatic delivery module (control circuit is shown in Fig. S2). The touch screen offered delivery parameters: delivery volume per pulse, interval time, and total delivery number. The operator then went to the working interface and clicked the WASHING button to activate the two 4-channel piston pumps. This step could clean the pipeline or rapidly fill the pipeline with titrant. In order to eliminate cross contamination, a separate micro-syringe with Teflon needle was used to load each different titrands into disposable reaction cells. Then, an oval mini magnetic rotor (2.8 mm in length) was put into each reaction cell. After inserting the reaction cells (in each 1.5 mL titrand was loaded), the operator ran the customized TEAM software to monitor the 8 simultaneous reactions. Unless otherwise stated, the apparent conductivities of the solution in the reaction cells were collected every 0.5 s. The operator then clicked the START button on the touch screen, and the electrical elevator mechanism lowered the 8-channel syringe needle array to a working location to ensure the effluent titrant could flow down along the wall of the reaction cells. An AC voltage (excitation frequency of 2.0 MHz and excitation amplitude of 16 V) was applied to each actuator electrode [23,26], and the apparent conductivity of the solution in the reaction cell was monitored in real time. While the 5 / 15

first apparent conductivity value in each cell was collected, titrant was beginning to be delivered simultaneously into each cell. Unless otherwise stated, 7.5 μL titrant was delivered in a 1 s pulse followed by a 1 s interval. The output data were saved as text files for further processing with Microsoft Excel to form titration curves. The endpoints were identified from the valleys of the Vshaped titration curves. The time span was defined as elapsed time from the beginning of the monitoring to the endpoint [23]. The concentrations of the titrand were obtained according to the consumption of titrant, which could be calculated from the elapsed time. At the end of one batch measurement, the electrical elevator mechanism automatically raised the 8-channel syringe needle array to facilitate reaction cell removal. The operator then repeated the measurement operation when another 8 reaction cells were inserted. The steps of the procedure, as well as the time needed for each step, were summarized in Table S1. Unless a requirement of titrant switch for another titration couple, the pipeline needed no cleaning or any other treatment. Contact conductivity measurements In case where it needed, the conductivities of solutions were measured in triplicate by a commercial conductometer (Seven Excellence S470-K, Mettler-Toledo) at room temperature with parameters suggested by the manufacturer. In order to eliminate the memory effect between each measurement, the contact working electrode and the reaction vessel were washed carefully with 0.1 M HCl and water, respectively, for 5 min. Analysis of batched vinegar samples The measurement of CH3COOH in vinegar samples was performed in 8 solution samples using fresh NaOH solution as titrant in octuplicate with delivery parameters as follows: 7.5 μL per pulse, interval 1 s and 30 deliveries in total. The vinegar samples were analyzed directly after they were diluted 10 times with water. The control experiments were performed by employing an 877 Titrino plus (Metrohm AG, Herisau, Switzerland) with parameters suggested by the manufacturer. Unless stated otherwise, the experiments were all carried out at room temperature (25 ± 1°C).

Results and discussion Characteristics of the 8-CET system The titrant delivery technique and the method for identifying endpoint are two key factors regarding the automation of titration [29]. In the 8-CET system, the delivery module and the monitoring module both

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play important roles to guarantee the accuracy and precision of titration. Therefore their properties were characterized carefully, following by optimizations. A piston pump is generally used for automatic titrations to realize delivery via a glass cylinder and a piston driver. It often has higher precision than a peristaltic pump [18]. Thus, two 4-channel piston pumps were employed in the 8-CET system. As shown in Table S2, the accuracy of the delivery depends on the volume per pulse. With the increase of delivery volume per pulse, both of the precision and the accuracy are higher. It is well known that smaller volumes of titrant per pulse result in higher resolution titrations. Thus, in all the other experiments, 7.5 μL per pulse was selected for a balance. In traditional titration, it is important that the droplets remain uniform and their size be controllable because the titrant flow is proportional to the droplet size and because the droplet size determines the smallest volume of titrant that can be delivered [29]. In our experiments, titrant flows down along the wall of the reaction cell as soon as it comes out the tip of the Teflon needle to guarantee parallel delivery. At room temperature, a series of KCl solutions at different concentrations were measured with the 8channel C4D, respectively. The apparent conductivity is in Table S3. Obviously, the apparent conductivity increases as a function of KCl concentration over the range of 0.01–0.2 M. From 0.01 M to 0.10 M, a sensitivity of ~ 14.00 V/M is obtained. As we showed previously [23,26], the relationship between the apparent conductivity and KCl concentration is slightly nonlinear because of the presence of a very small capacitive coupling between the two electrodes [30]. Meanwhile, due to minor variations in the physical size of the reaction cells and their coupling to the electrodes, there are small variations of apparent conductivity of the same solution even when measured in the same channel (RSD < 0.6%, n = 9). However, the former phenomenon does not negatively impact the titration [23]. The latter can be improved using standard sized reaction cells. Performance of multichannel acid-base titration The C4D-based titration method is a versatile platform for all four routine titrations, i.e. acid-base, precipitation, complexation, and redox titrations [23]. Here the capacity of the 8-CET system for an acid-base titration was evaluated by simultaneously measuring HCl at different concentrations (10.0, 20.0, 30.0, 40.0 and 50.0 mM) using 50.0 mM NaOH as the titrant. A typical graph of apparent conductivity versus titration time is shown in Fig. 2A. Upon addition of OH−, H2O is formed in titrand solutions, causing net decreases in conductivity over the first stage. As soon as all of H+ is consumed 7 / 15

by added OH−, the net conductivity increases due to the added OH− and Na+ ions [31]. As expected, all curves are nonlinear because of the dilution effects [17], but this does not affect endpoint determination [23]. These V-shaped titration curves show that different elapsed times result from the different initial concentrations of titrands (HCl solutions). The endpoint can be identified easily from the valley of the V-shaped curve. This user experience is much better than identifying the endpoint with graphical method on screen or paper [8,18,32,33]. It is especially worth noting that when there is lack of stirring, the amount of consumed titrant is more than theoretical one due to the slow mass transfer [27]. In order to decrease the turnaround time, as well as to obtain more robust measurement. Here, an array of automated stirring device was used in the 8-CET system. It helped to realize stoichiometric titration and saved titrant.

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Fig. 2 (A): Typical titration curves of HCl solutions at different concentrations titrated with 50.0 mM NaOH performed with the 8-CET system. From a to e the concentration of titrand (HCl solutions) was 10.0, 20.0, 30.0, 40.0 and 50.0 mM, respectively. (B): Plot of the elapsed time versus the initial concentration of HCl solutions. (C): Plot of the NaOH consumption versus the initial concentration of 8 / 15

HCl solutions. (D): Typical titration curves of HCl solutions at different concentrations titrated with 50.0 mM NaOH when “set channel all offset auto” instruction was issued. Delivery parameters: 7.5 µL per pulse at a 1 s interval; temperature: 25 ± 1°C; the apparent conductivity values were collected at a 0.5 s interval; 1.5 mL titrand was loaded in each reaction cell.

Fig. 2B shows that the elapsed time increases linearly with the initial concentration of titrands across the range of concentrations measured (experiments in triplicate) indicating that there are robust relationship between the amount of titrand and the consumption of titrant. This allows the construction of a reliable quantitative measurement of target substances [8]. Fig. 2C confirms this and shows that there is a good precision. During traditional electrochemical titration [8,19-22], the tips of the working electrode and reference electrode (if there is one) must be immersed in the solution rather than a non-invasive test [17,20] causing two bothersome consequences: 1) Electrode deterioration is unavoidable [34] and this results in erratic measurements that decrease the accuracy; and 2) Electrodes and reaction cells must be cleaned before each measurement to minimize the memory [19]. Here, we developed the C4Ds to monitor the conductivity of solutions with a non-invasive mode which solved this problem. This makes it be viable to realize simple and multichannel titration because the cells are disposable. We tested the precision with 20.0 mM HCl titrated with 50.0 mM NaOH in quintuplicate. The RSD of the determination results for all channels was no more than 2.1%. The 8-CET system also provides a special mode to form a unique type of titration curves. When all the reaction cells were inserted into the channels, we inputted an instruction “set channel all offset auto”. The system spent about 10 s measuring, averaging and determining the zero offset on each channel and apply an adjustment to reduce the typical zero error. Next, titration was performed via conductivity measurements. The apparent conductivity in each reaction cell is considered as “zero”. This also results in V-shaped titration curves. When 10.0, 20.0, 30.0, 40.0 and 50.0 mM HCl solutions were titrated simultaneously with 50.0 mM NaOH, the typical titration curves are showed in Fig. 2D. Though the relationship between the elapsed time and the initial concentration of titrands obtained from this Figure is the same as obtained from Fig. 2A, this titration curve explains the net change in conductivity during the titration reaction. Performance of multichannel precipitation titration

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The formation of a precipitate or precipitates alters the number of ions present in the titration solution and in turn changes the conductivity [17,32]. Referring to the method reported previously [17,23], the capacity of the 8-CET system for precipitation titration was evaluated using classical Cl− – Ag+ reaction. Fig. 3A shows typical graphs of apparent conductivity versus titration time when 30.0, 40.0, 50.0, 60.0, 70.0, 80.0, 90.0 and 100.0 mM KCl solutions were titrated simultaneously with 100.0 mM AgNO3. It is clear that the elapsed time increases linearly with the initial concentration of titrands (Fig. 3B), suggesting the feasibility of a quantitative measurement. When 50.0 mM KCl was titrated with 100.0 mM AgNO3, repeat experiments show that the RSD of measurement results (amount of KCl in mol) is no more than 2.2% for each channel. Five replicate titrations were performed the next day to test the day-to-day reproducibility. The RSD of measurement results agrees with the previous day. 110

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Fig. 3 (A): Titration curves of KCl solutions at different concentration titrated with 100.0 mM AgNO3, performed by the 8-CET system. From a to h the concentration of titrand (KCl solutions) was 30.0, 40.0, 50.0, 60.0, 70.0, 80.0, 90.0 and 100.0 mM, respectively. (B): Plot of the elapsed time versus the initial concentration of KCl solutions. Delivery parameters and other conditions are the same as in Fig. 2. Application to measure batched vinegar samples Food-grade vinegar solution at a certain concentration is often used as seasoning (vinegar), and there is a big need for high throughput industrial analysis to control the quantity [35]. Here, a batch of vinegar samples was measured using the 8-CET system in comparison to a traditional automatic titrator. The acid-base reaction occurred in the following equation: 𝐶𝐻3𝐶𝐻𝑂𝑂 ‒ + 𝐻 + + 𝑁𝑎 + + 𝑂𝐻 ‒ → 𝐶𝐻3𝐶𝐻𝑂𝑂 ‒ + 𝑁𝑎 + + 𝐻2𝑂 10 / 15

The titration curves show declines in apparent conductivity down to the endpoint, attributing to the formation of H2O. After the endpoint, the net conductivity increases rapidly due to the addition of highly mobile OH− and Na+ ions [31]. Thus a titration measurement can be performed. First, measurements were performed to obtain the maximum and minimum limits of CH3COOH concentration under selected titration parameters. Using 100.0 mM NaOH as the titrant, a series of standard CH3COOH solutions at different concentrations were measured with the 8-channel C4D, respectively. The results are shown in Table 1. From these results we inferred that the optimal determinable concentration range was 2.0 to 10.0 g/L. The declared concentration of six vinegar samples we obtained was 57.0 g/L. The remainder were 45.0 g/L. Thus, these were diluted 10 fold with water before titration. Table 1 Measurement results of standard CH3COOH at different concentration with the 8-CET system. CH3COOH concentration (g/L) 0.8 1.0 2.0 4.0 6.0 8.0 10.0 12.0 a

Measurement results (g/L) a 0.91 1.22 2.20 4.15 5.93 8.14 9.86 11.89

Standard Deviation (g/L) 0.26 0.12 0.10 0.10 0.09 0.08 0.08 0.11

Average value of eight measurements.

The titration results of vinegar samples are presented in Table 2. One can see that there is good agreement between the results obtained with the two methods, including the precision. While, by employing the 8-CET system the 8 samples were determined within 1 min; in contrast, 100 min is needed with the 877 Titrino plus including the time consumption for washing the reaction cell and electrode. Therefore, this new multichannel system is obviously superior to those single channel titrators in efficiency [23,27]. Table 2 Measurement results of CH3COOH concentration in 8 vinegar samples with the 8-CET system and with the reference traditional titrator. Sample number 1 2 3 4 5 6 7 8

Declared Concentration (g/L) 57.0 57.0 57.0 57.0 57.0 57.0 45.0 45.0

Measurement with 8-CET system Concentration (g/L) 56.6 57.1 57.1 57.1 56.9 56.8 45.2 44.9

a

a

RSD (%) 2.2 2.2 1.9 2.3 2.0 2.3 2.2 2.0

Measurement with 877 Titrino plus concentration (g/L) a 56.5 56.6 56.9 57.0 56.7 56.6 45.2 44.7

Average value of five measurements. 11 / 15

RSD (%) 2.3 2.0 1.9 2.3 2.1 2.4 2.2 2.0

In classical electrochemical titration [8,19-22], manual washing of the reaction cell and working electrode is critical to eliminate the memory effect [19,23]. By employing the C4D and a disposable reaction cell, our approach does not require these wash steps making it practicable to construct multichannel titrator. Moreover, conductivity measurements allow a much fast detection because there is no equilibration of the electrodes [18]. This also helps to improve the efficiency of titration. While, optical technique (e.g. digital movie [4]) is an alternative promising method to realize multichannel titration because of the non-invasive test. However, a step for the addition of indicator is often required [9,15,16]. And the performance is confined to transparent solution and vessel [21,23]. Therefore, in contrast, the C4D is more suitable for use in constructing a multichannel titrator, and titration can be significantly simplified. In addition, the precision and uniformity of titrations were also evaluated when the 8-CET system was applied to measure vinegar samples. Eight copies of the same vinegar sample (No. 1) were loaded in 8 reaction cells (1.5 mL/cell), respectively. Nearly identical V-shaped titration curves were obtained when they were measured simultaneously (as showed in Fig. S3). The RSD of the measurement results is 1.9%. Reproducibility was assessed by titrating the sample on different days (n = 3), and the RSD was from 2.3 to 4.4%. In order to verify the applicability of the proposed method in laboratory and industry, studies of recovery were carried out with spiked samples at three concentrations. Because 8 samples could be measured simultaneously, experiments were performed in octuplicate. One can see from Table 3 that the recoveries are between 98.8%–101.2% with RSD of 1.4–1.8%, indicating a satisfactory accuracy and repeatability. Table 3 The results of accuracy (n = 8). Spiked (g/L) 4.0 5.0 6.0

Mean recovered 3.95 5.06 5.95

RSD 1.7% 1.8% 1.4%

Mean recovery 98.8% 101.2% 99.2%

Conclusion Here, we used an eight-channel C4D and piston pumps to construct a multichannel and automatic titrator (we called this an 8-CETsystem). Using disposable glass tubes as reaction cells, batched measurements could be accomplished simultaneously. The proposed device is easily miniaturized because it employs an electronic sensor [8]. It is simple and avoids switching the working electrode. In the performance of titration there is no cleaning step for both working electrode and reaction cell. The 12 / 15

8-CET system can perform acid-base and precipitate titrations. Furthermore, it can also be used for redox and complexation titrations [17,23]. In the batched vinegar assay, it demonstrates excellent precision, efficiency, and simplicity. The system cost only a few thousand dollars including the hardware and software development. When it is commercialized, this apparatus will be affordable for a common laboratory even in lowresource settings. In principle, the 8-CET system can incorporate all electronic components into a single compact module. Thus, we can minimize the bulk of the instrument further to save on limited bench space in the laboratory and realize point-of-care usage.

ACKNOWLEDGEMENTS This work was supported by the National Key R&D Program of China (2017YFE1015200) and the Special Scientific Research Funds for Central Non-profit Institutes, the Yellow Sea Fisheries Research Institute, the Chinese Academy of Fishery Sciences (20603022018020, 20603022016003).

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High-throughput C4D is used to simultaneously monitor multichannel titrations. > Portable, versatile and affordable electronic sensor-based titrator is developed. > Simple and efficient operation is realized by avoiding the treatment of electrodes.

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