Miniaturized Bio-and Chemical-Sensors for Point-of-Care Monitoring of Chronic Kidney Diseases

Abstract

This review reports the latest achievements in point-of-care (POC) sensor technologies for the monitoring of ammonia, creatinine and urea in patients suffering of chronic kidney diseases (CKDs). Abnormal levels of these nitrogen biomarkers are found in the physiological fluids, such as blood, urine and sweat, of CKD patients. Delocalized at-home monitoring of CKD biomarkers via integration of miniaturized, portable, and low cost chemical- and bio-sensors in POC devices, is an emerging approach to improve patients' health monitoring and life quality. The successful monitoring of CKD biomarkers, performed on the different body fluids by means of sensors having strict requirements in term of size, cost, large-scale production capacity, response time and simple operation procedures for use in POC devices, is reported and discussed.

Keywords: POC testing devices; biosensors; chemical sensors; kidney disease.

Figure 1

Renal biomarker development. Approach to renal biomarker discovery and clinical applicability. B2M, b-2-microglobulin; BUN, blood urea nitrogen; FABP, fatty acid-binding protein (types L and H); KIM-1, kidney injury molecule 1; NAG, N-acetyl-β-D-glucosaminidase; NGAL, neutrophil gelatinase-associated lipocalin; NP, natriuretic peptide. Reprinted from [10].

Figure 2

Schematic of the assembled multi-layer system. Reprinted from [28].

Figure 3

(a) Schematic drawing of a prototype sensor (glass/Ag/ZnO NRs/urease) for urea sensing, (b) CVs of urea sensor in absence and presence of 0.5 mM urea at 50 mV/s scan rate in PBS (pH 7); (c) CVs at different scan rates, 20–160 mV/s, and (d) magnitudes of peak oxidation (I_pa) and reduction (I_pc) currents as a function of (scan rate)^1/2. Reprinted from [29].

Figure 4

Patch developed at the University of Cincinnati using paper microfluidics to wick sweat from the skin through a selective membrane. Onboard circuitry calculates the ion concentration and sends the data to a smartphone. The electronics within the patch are externally powered, as in an RFID chip. Reprinted from [33].

Figure 5

(a) Image of the sweat extraction and sensing platform; (b) Image of iontophoresis and sweat sensor electrodes for sodium and chloride ion sensing; (c) Schematic illustrations of the iontophoresis and sensing modes; (d) Block diagram showing the iontophoresis and sensing circuits. Reprinted from [35].

Figure 6

Differential pulse voltammograms of different concentrations of creatinine solutions (a) and Nyquist plots of different concentrations of creatinine solutions (b) in 5.0 mM[Fe (CN)6]³⁻ and 5.0 mM [Fe (CN) 6]⁴⁻ in PBS buffer at pH 7.4. Z’ and Z’’ in Figure 6b represent the real and the imaginary part, respectively, of the impedance. Reprinted from [43].

Figure 7

Potential-time plot for different creatinine concentrations of the calix [4] pyrrole-based sensor. Inset is reported the calibration curve (RSD 0.6% for N = 5). Reprinted from [46].

Figure 8

(a) Inkjet-printed ammonia sensor; (b) POC device for measuring breath ammonia levels; (c) Breath ammonia measured in patients with end-stage kidney disease before and after dialysis. Reprinted from [65].

Figure 9

(a) Cylindrical nanopore structure of poly[(9,9-dioctylfluorenyl-2,7-diyl)-co-(4,4′-(N-(4-s-butylphenyl))diphenylamine)] (TFB) sensing material; (b) Analysis of the breath profile of patients before and after dialysis. Reprinted from [67].

Figure 10

(a) Description of devices; (b) Calibration curve. Reprinted from [69].

Figure 11

Schematic description of continuous real-time breath analysis system. (a) Participants breathed through a sterile mouthpiece without resistance. Ex- and inhaled breath was transferred continuously into the heated transfer line (connected via t-piece) of the PTR-ToF-MS in a side-stream mode at a flow of 20 mL/min; (b) Every 200 ms a TOF—mass spectrum was recorded. Reprinted from [55].