Chip-based ion chromatography (chip-IC) with a sensitive five-electrode conductivity detector for the simultaneous detection of multiple ions in drinking water

The study addresses the need for accurate, inexpensive, and convenient monitoring of regulated anions (F⁻, Cl⁻, NO₃⁻, SO₄²⁻) in drinking water, given health risks and guideline limits. Conventional ion chromatography (IC) offers quantitative, simultaneous multi-ion analysis but is bulky for field use. Prior lab-on-a-chip advances in GC and LC have not fully translated to IC due to integration challenges (on-chip valves, high-pressure-resistant bonding, robust packed columns) and the lack of a sensitive, compact on-chip detector for nonsuppressed operation. The research aims to develop a compact, integrated chip-IC platform that can separate and sensitively detect multiple anions in drinking water with performance comparable to benchtop IC while enabling portability.

Previous chip-IC efforts packed anion-exchange resin into microchannels (e.g., silicon or PMMA) but relied on external syringe pumps, injectors, and detectors, limiting integration. On-chip column formats include open-tubular, monolithic, and pillar arrays; however, packing commercial beads into channels with frits is straightforward and reproducible, though it demands strong interfacial bonding to withstand high pressures. Common frit designs (weirs, step channels, parallel small channels) involve complex fabrication and bonding challenges. PDMS is unsuitable for chip-LC/IC due to gas permeability and weak bonding. On-chip injection often uses T- or cross-junctions but still requires external valves; integrated microvalves face high-pressure constraints and heterogeneous interface bonding issues. Conductivity detection (CD) is the universal detector for IC. Suppressors improve sensitivity in macro-IC but are difficult to integrate on-chip; nonsuppressed CD with low-conductivity eluents is more suitable. Contact CD is more sensitive than contactless but suffers from Faradaic reactions and baseline noise unless the electrode configuration mitigates these effects. These gaps motivate an integrated, high-pressure-capable chip with a sensitive, low-noise contact CD suitable for nonsuppressed IC.

System design and setup: A compact chip-IC platform integrates an IC chip, signal-conditioning electronics (data processing circuit), and a DAQ in a 3D-printed enclosure (17 × 19 × 10 cm³; <2 kg). Eluent is delivered by an external conventional LC/syringe pump connected via PEEK fittings. The chip incorporates sample injection microvalves, a packed separation column, and a five-electrode contact conductivity detector. On-chip sample injection and valves: The injection sequence includes (i) baseline stabilization with eluent, (ii) opening two on-chip valves to load sample from the inlet, and (iii) closing valves sequentially to define and inject the sample plug into the packed channel. Valves are screw-driven (with a ball pressing a membrane against a hemispherical chamber) but can be automated using micromotors or solenoids. Five-electrode conductivity detector: The electrodes comprise two reference electrodes (E1, E4), two sensing electrodes (E2, E3), and a ground (E5). A sinusoidal current applied to E1/E4 is modulated to maintain a constant potential drop between E2 and E3 via a feedback loop (differential amplifier DA1 controlling a variable AC generator). The current change is read across a sampling resistor, processed by DA2, and measured by a voltmeter/DAQ. The ground electrode reduces capacitive leakage. The configuration minimizes Faradaic currents at sensing electrodes, stabilizing the baseline and improving S/N for nonsuppressed detection. Chip fabrication: Single-layer PMMA chips with channels, cavities for frits, valve membranes, and electrode seats were prototyped by micromilling. After cleaning and assembly of frits, membrane disks, and electrodes, laser bonding sealed both homogeneous (PMMA/PMMA) and heterogeneous (PMMA/frit, PMMA/membrane, PMMA/electrode) interfaces. Infrared monitoring showed localized heating and melting with minimal heat-affected zones; molten PMMA filled interfacial gaps, ensuring robust seals. Mechanical and pressure performance: Tensile tests on bonded PMMA (1.5 × 2 mm² cross-section; pull rate 1 mm/min) yielded an average normal strength of 74.5 MPa (RSD 0.64%, n=8), with most fractures outside the bonded interface. Burst tests recorded 10.6 MPa, with leakage at world-to-chip connections, indicating ample strength for column packing and operation. Column packing and quality: Columns were slurry-packed with commercial anion-exchange beads using embedded sintered frits to retain particles. Flow-resistance factor ϕ was computed from measured pressure-flow data using DI water, yielding ϕ ≈ 650 (within the typical 500–1000 range), indicative of good packing without voids/cracks. The design and packing achieved higher ϕ than prior parylene channels with the same beads, suggesting improved packing quality. Operating conditions and analytics: For detector characterization and separations, eluents used included 4 mM p-hydroxybenzoic acid (p-HBA) with 2.5% methanol at pH 8.5 (nonsuppressed mode). Typical flow rates were 10–25 µL/min; injection volume was ~0.5 µL; ambient temperature detection. Standards tested included SO₄²⁻ at 5–100 mg/L (triplicates) and mixtures: (1) 10 mg/L Cl⁻, 20 mg/L NO₃⁻, 20 mg/L SO₄²⁻; (2) 50 mg/L F⁻, 10 mg/L Cl⁻, 30 mg/L NO₃⁻, 20 mg/L SO₄²⁻. Tap water samples were collected, filtered, and analyzed at 7 am and 7 pm; results were benchmarked against a commercial benchtop IC (IC-8286).

- Integration and robustness: The PMMA chip integrates on-chip microvalves, a packed column, and a five-electrode contact CD, all sealed via laser bonding. Bond strength averaged 74.5 MPa; burst pressure reached 10.6 MPa (failure at external connection), sufficient for high-pressure packing and operation. - Column quality: The packed column exhibited a flow-resistance factor ϕ ≈ 650 (DI water), within the typical 500–1000 range, indicating good packing quality. - Detector performance: The five-electrode detector provided a stable baseline and improved S/N suitable for nonsuppressed IC. - Calibration and sensitivity: For SO₄²⁻ standards (5–100 mg/L) at 25 µL/min, linearity R² = 0.996 (n=3 per level). RSDs: retention time 0.2–0.5%, peak height 0.6–2.4%. LOD (S/N=3) for SO₄²⁻ was 0.6 mg/L. - Separation speed and efficiency: Common anions (F⁻, Cl⁻, NO₃⁻, SO₄²⁻) were separated in <8 min at 25 µL/min, though F⁻ and Cl⁻ overlapped under current nonsuppressed conditions; software deconvolution could resolve them. Decreasing flow rate improved resolution at the cost of analysis time. Theoretical plates (plates/m) increased as flow decreased from 25 to 10 µL/min: Cl⁻ ~3800–7100, NO₃⁻ ~7100–11,200, SO₄²⁻ ~6100–9600. - Tap water analysis: The chip-IC quantified anions in tap water at room temperature with relative deviations <10% compared to a commercial IC system, demonstrating practical applicability. - System footprint: The packaged system (17 × 19 × 10 cm³; <2 kg) supports portability for field-relevant water testing.

The work demonstrates that a compact, integrated chip-IC platform can achieve quantitative, multi-analyte anion detection in drinking water with performance metrics approaching benchtop IC. The five-electrode contact CD stabilizes the baseline and enhances sensitivity under nonsuppressed conditions, addressing a key bottleneck in chip-IC. Laser bonding of PMMA enables reliable sealing across both homogeneous and heterogeneous interfaces, making on-chip bead packing and high-pressure operation feasible. The observed linearity, low LOD for SO₄²⁻, acceptable precision, and agreement with benchtop IC validate the analytical capability. While overlap between F⁻ and Cl⁻ under the current eluent and nonsuppressed mode limits direct peak resolution, it can be mitigated via software deconvolution or improved with optimized resins and buffer conditions. Overall, the system advances the miniaturization of IC for practical, portable water quality monitoring without requiring an on-chip suppressor.

This study introduces a fully integrated PMMA-based chip-IC system incorporating on-chip microvalves, a slurry-packed column, and a five-electrode contact conductivity detector, all robustly sealed via laser bonding. The platform achieves fast (<8 min) separation of common anions, sensitive detection (SO₄²⁻ LOD 0.6 mg/L), good linearity and precision, and accurate quantification in tap water with <10% deviation from a commercial IC. Mechanical strength and burst pressure testing confirm suitability for high-pressure chromatographic operation, and packing metrics indicate high-quality columns. Future work should focus on integrating compact pumps and automated valve actuation for full portability, optimizing stationary phase and eluent to resolve F⁻/Cl⁻ directly, expanding the analyte panel, and exploring on-chip suppressor integration to further enhance sensitivity.

- Overlap of F⁻ and Cl⁻ under current nonsuppressed conditions and eluent composition; resolution relies on post-processing or method optimization. - System still utilizes an external pump; current valves are screw-driven rather than fully automated on-chip actuation. - Nonsuppressed detection is susceptible to a large water dip, potentially affecting weakly retained species. - Sensitivity and calibration data were detailed primarily for SO₄²⁻; broader LOD/LOQ characterization for other anions was not provided. - Validation was demonstrated on tap water with limited sampling times; broader environmental matrices and long-term stability studies were not reported.