APL: L14-11037R Supplementary materials Complex Permittivity Characterization of Serum with an Air-Bridge Enhanced Capacitor for Quantifiable Detection of Glucose Rajendra Dhakal1, a), Cong. Wang1, Eun-Seong Kim1 and Nam-Young Kim1, b) 1 RFIC Centre, Department of Electronic Engineering, Kwangwoon University, Seoul 139- 701, South Korea FIG. S1. Schematic of the RF detection technique by vector network analyzer (Agilent 8510C). 1 FIG. S2. Regression analysis of the real sample of serum for different experiment time. The generated result for the experiment time interval of 40 sec shows a maximum shift. The response quality degrades as the experiment times increased to 160 sec. FIG. S3. Equivalent circuit model of the fabricated IPD glucose sensor. 2 (a) (b) FIG. S4. Measurement results showing (a) the [Real {εr (ω)}] and [Imag{εr (ω)}] part of complex permittivity variation with different glucose concentration level. (b) The magnitude of εr (ω) obtained by the numerical formulation. 3 (a) (b) FIG. S5. The measurement illustration of D-glucose solution for (a) the microwave transmission coefficient with different concentration of glucose level (n = 10). The bare resonance frequency at 7.37 GHz, 7.35 ± 0.20% GHz at 25 mg/dl, 7.27 ± 0.21% GHz at 50 mg/dl, 7.21 ± 0.21% GHz at 75 mg/dl, 7.15 ± 0.14% GHz at 100 mg/dl, 7.08 ± 0.21% GHz at 125 mg/dl, 7.01 ± 0.21% GHz at 150 mg/dl, 6.93 ± 0.14% GHz at 175 mg/dl, 6.85 ± 0.23% GHz at 200 mg/dl, 6.78 ± 0.22% GHz at 225 mg/dl, 6.71 ± 0.15% at 250 mg/dl. (b) The regression analysis with standard error bar for n = 10 at various concentration of the D-glucose level. The standard sample of deionized water glucose solution possesses slightly different characteristic features to the real sample of serum. Because of this inconsistency 4 between the standard and real sample, we obtained a slightly different calibration equation for the real sample of serum and D-glucose solution, but the nature of the calibration curve and shift in the resonance frequency coincide with the real sample. We used the standard sample of D-glucose to model and monitor the trend of resonance characteristics for a relative shift in the resonance frequency for different glucose concentrations in order to verify the finding obtained from the real sample of the serum. The obtained measurement results for the D-glucose solution validate the proposed concept of glucose level detection with excellent detection capability having a minimum detection limit as small as 10.22 mg/dl. FIG. S6. Scattering plot of the serum sample for 30 different experiment process with different glucose concentration. The observed data show no overlapping of the resonance frequency among the different concentrations for different sets of the experiment. The reproducibility of the biosensor was characterized by measuring the resonance frequency before and after the use of serum. We performed three different sets of experiments for each concentration of serum to observe the resonance frequency for each-iteration loop of the experiment. A total of 30 different experiments for a sample of the serum was tested and represented by the scatter plot. No device response deterioration was observed over this long iteration of the measurement process. As a result, the relative standard deviation (RSD) of less than 1% was observed for each concentration of serum samples. This observation validates that the proposed device can reproduce the same experiment result for particular concentrations over different iteration of the experiments. The bare resonance frequency from each set of experiments after rinsing was obtained at 7.37 GHz, which confirms the stability and reusability of the system. 5 Table S1 The performance of the different measurement parameters for the serum sample having the base glucose concentration of 65 mg/dl. a S.N Human serum b e Con. Resonance frequency (GHz) RSD st nd rd c d (mg/dl) 1 Test (%) 2 Test 3 Test Mean Mean ± RSD ( fav) 1 245 6.82 6.83 6.84 6.83 6.83 ± 0.14% 0.14 2 225 6.88 6.9 6.87 6.88 6.88 ± 0.22% 0.22 3 205 6.94 6.95 6.93 6.94 6.94 ± 0.14% 0.14 4 185 7 7.01 7.02 7.01 7.01 ± 0.14% 0.14 5 165 7.07 7.09 7.07 7.07 7.07 ± 0.16% 0.16 6 145 7.12 7.11 7.13 7.12 7.12 ± 0.14% 0.14 7 125 7.18 7.16 7.17 7.17 7.17 ± 0.14% 0.14 8 105 7.23 7.22 7.24 7.23 7.23 ± 0.13% 0.13 9 85 7.28 7.26 7.28 7.27 7.27 ± 0.15% 0.15 10 65 7.33 7.32 7.31 7.32 7.32 ± 0.13% 0.13 11 Bare Test 7.37 7.37 7.37 7.37 7.37 ± 0% 0 a S.N denotes serial number. b Con. denotes the glucose concentration. c Mean denotes the average of the three experiments. d fav denotes final average resonance frequency. e RSD denotes the relative standard deviation. Table S2 The performance of the different measurement parameters for the D-glucose sample having the base glucose concentration of 25 mg/dl. a S.N D-glucose b e Con. Resonance frequency (GHz) RSD st nd rd c d (mg/dl) 1 Test (%) 2 Test 3 Test Mean Mean ± RSD ( fav) 1 250 6.71 6.73 6.72 6.72 6.72 ± 0.15% 0.15 2 225 6.78 6.8 6.77 6.78 6.78 ± 0.22% 0.22 3 200 6.85 6.87 6.84 6.85 6.85 ± 0.23% 0.23 4 175 6.93 6.92 6.91 6.92 6.92 ± 0.14% 0.14 5 150 7.01 7.03 7 7.01 7.01 ± 0.21% 0.21 6 125 7.08 7.09 7.06 7.07 7.07 ± 0.21% 0.21 7 100 7.15 7.14 7.16 7.15 7.15 ± 0.14% 0.14 8 75 7.21 7.2 7.23 7.21 7.21 ± 0.21% 0.21 9 50 7.27 7.25 7.28 7.26 7.26 ± 0.21% 0.21 10 25 7.35 7.33 7.32 7.33 7.33 ± 0.20% 0.20 11 Bare Test 7.37 7.37 7.37 7.37 7.37 ± 0% 0 a S.N denotes serial number. b Con. denotes the glucose concentration. c Mean denotes the average of the three experiments. d fav denotes final average resonance frequency. e RSD denotes the relative standard deviation. 6 Table S3 Comparative performance of the proposed IPD glucose sensor with previously reported articles. Literature 28 Proposed method Forster resonance energy transfer (FRET) 29 Impedance spectroscopy 30 Magnetic acoustic resonance sensor (MARS) This work IPD based RF resonator on GaAs substrate by characterization of complex permittivity Advantages Reversibility Implanted sensor Disadvantages LOD (mg/dl) Long assay time 25 (15 min), high LOD Complex process, 12.02 high LOD Invasive, high LOD 36.36 Short assay time, highly sensitive reusability, mediator free detection High production cost and low running cost via reusability Sensitive 9.69 Table S4 Demonstrating the effect of fructose in the glucose concentration for the blood serum samples. # Sample Glucose Glucose concentration Added Glucose concentration concentration determines, before the fructose determines, after the addition (mg/dl) addition of fructose with RSD (mg/dl) of fructose with RSD (mg/dl) (mg/mL) ±RSD% ±RSD% 1 105 104.66 ± 0.40 20 104.53 ± 0.48 2 145 147.16 ± 0.85 20 147.33 ± 0.85 3 205 204.33 ± 0.39 20 204.4 ± 0.70 # Each sample was measured three times. 7