SLIPS-LAB—A bioinspired bioanalysis system for metabolic evaluation of urinary stone disease

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Science Advances  22 May 2020:
Vol. 6, no. 21, eaba8535
DOI: 10.1126/sciadv.aba8535
  • Fig. 1 Slippery Liquid-Infused Porous Surface Laboratory.

    (A) Schematic for rapid metabolic evaluation of urinary stone disease using SLIPS-LAB in point-of-care settings. SLIPS-LAB detects urinary stone–associated analytes from sample to result in 30 min, in contrast to over 1 week in the current workflow. SLIPS-LAB will potentially enable frequent multiplex metabolic analyses, improve patient adherence to medication or dietary interventions, and assess treatment response. (B) The stand-alone SLIPS-LAB device is designed to perform fluid sampling, volume metering, droplet transportation, and biochemical reactions for multiplex metabolic analyses without the requirement of bulky supporting equipment. Reagents can be loaded into the device by dipping SLIPS-LAB into the reservoir. Fluid droplets are transported by a force imbalance induced geometrically on the SLIPS-coated channel. The samples and reagents are mixed in the reaction chamber for detecting analytes colorimetrically and enzymatically. (C) Autonomous transportation of viscous fluids and biological fluids in a multiplex SLIPS-LAB device. The viscosity of the water, milk, grape juice, glycerol, maple syrup, and honey spans over three orders of magnitude. SLIPS-LAB also transports physiological fluids including urine, saliva, tracheal aspirate (TA), plasma, and whole blood. Images are representative of at least two independent experiments. Scale bar, 5 mm. Photo credit: Hui Li (The Pennsylvania State University).

  • Fig. 2 Working principles of SLIPS-LAB.

    (A) SLIPS-LAB performs common biochemical procedures, including volume metering, liquid handling, reaction time control, and detection. Images are representative of two independent experiments. Scale bars, 2 mm. (B) Loading and metering of small-volume liquids in the top inlet by capillary force. (C) Sampling of large-volume liquids in the bottom inlet with air pressure by sealing the air hole. (D and E) Liquid transportation driven by the geometry-induced force imbalance on SLIPS, which has low contact angle hysteresis. The loading speed can be adjusted by the channel geometry to control the reaction sequence and the delay time for multistep reactions. (F) Reactions occur after merging and mixing of droplets in the reaction chamber. (G and H) Evaluation of volume metering for small-volume (<15 μl) and large-volume (>15 μl) liquids. D is the top inlet diameter. H is the dipping height of the liquid. (I) Controlling the loading time by the converging angle and channel thickness. T is the thickness of the channel. The loading time can be adjusted from a few seconds to ~4 min. Data represent mean ± SEM (n = 10 to 30).Photo credit: Hui Li (The Pennsylvania State University).

  • Fig. 3 The design of a multiplex SLIPS-LAB for urinary stone disease metabolic workup.

    (A to C) A six-plex SLIPS-LAB for detecting urinary stone–associated analytes. Top and side views of the device are shown in (A) and (B), respectively. T1 and T3 indicate the thicknesses of the bottom inlets (channel thickness). T2 and T4 indicate the thicknesses of the top inlets (PDMS thickness). T1, T2, T3, and T4 can be adjusted independently to control the sample and reagent volumes. Dotted circles indicate the air holes. Asterisks in (B) indicate positions of the top inlets. Zoom-in views of the top inlets are shown in (C). Color dyes are loaded in the device for visualization. Scale bars, 5 mm (A and B) and 1 mm (C). (D) Operation of the six-plex SLIPS-LAB device. Box 1 indicates loading of reagents for calcium, citrate, and uric acid detection. Box 2 indicates loading of reagents for oxalate detection, which requires two steps and a time delay of at least 3 min between the reactions. Box 3 indicates droplet transport for pH detection and control. (E) Reagents, volumes, and loading times of SLIPS-LAB inlets for urinary stone metabolic workup. (F) Calibration of the colorimetric and enzymatic assays for urinary stone–associated analytes. Data color (red, green, and blue) represents the RGB element used in the image. Data represent mean ± SEM (n = 3). a.u., arbitrary units. (G) Detection of urinary stone–associated analytes in a spot urine sample by SLIPS-LAB. The results are compared with the data obtained by the manufacturer-recommended manual procedures in 96-well plates (standard method). Data represent mean ± SEM (n = 3 for SLIPS-LAB and n = 2 for standard method).Photo credit: Hui Li (The Pennsylvania State University).

  • Fig. 4 SLIPS-LAB for urinary stone disease metabolic workup with patient urine samples.

    (A) Procedures for SLIPS-LAB metabolic workup with 24-hour urine samples. Urine samples were collected as part of routine clinical care under an exempted institutional review board protocol. The results were compared with clinical reports from a clinical diagnostic service provider (Quest Diagnostics). (B) Linear regression analyses of the data from SLIPS-LAB and the clinical reports. Data represent mean ± SEM (n = 3). (C) Bland-Altman plots for comparing results from SLIPS-LAB and the clinical reports. The plot examines the agreement between two methods and identifies systematic errors and outliers for data analysis. Red lines represent the mean. Cyan lines represent mean ± 1.96 SD or 95% limits of agreement. Red data points represent outliers determined using the Modified Thompson Tau method. (D and E) Heat maps of patients’ metabolic profiles obtained by SLIPS-LAB and the clinical reports. Color bars represent normalized concentrations and pH values. Photo credit: Hui Li (The Pennsylvania State University).

Supplementary Materials

  • Supplementary Materials

    SLIPS-LAB—A bioinspired bioanalysis system for metabolic evaluation of urinary stone disease

    Hui Li, Eugene Shkolyar, Jing Wang, Simon Conti, Alan C. Pao, Joseph C. Liao, Tak-Sing Wong, Pak Kin Wong

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