Indium Tin Oxide Coated Surface Plasmon Resonance Based Biosensor for Cancer Cell Detection Abstract—This A novel conventional single-core SPR-based cancerous or malignant cell detector sensor is demonstrated for the rapid identification monitoring cancer-affected distinct cell types. Each cancer-infected cell's refractive index (RI) is contrasted to such RI of its own healthy individual, and significant variations in optical properties are discovered. Moreover, the concentration of cancerous cells in liquid is estimated at 80%, as well as the finite element method (FEM) is used for detection (FEM). A thin Indium Tin oxide (ITO) film coating (50 nm) separates the silica and cancer cell parts, allowing for a plasmonic band gap to vary the spectral shift. The suggested sensor has a significant level of birefringence of 0.035 and a length of the coupling of up to 70 µm. On the other hand, the proposed model gives an ideal wavelength sensitivity level between around 10357.14 nm/RIU and 17750 nm/RIU, with a sensor resolution of 1.41×10-3 RIU and 7.37×10-3 RIU. In addition, the transmittance variance of cancerous cells varies from nearly 4100 dB/RIU to 6800 dB/RIU, in primary polarization mode, the amplitude sensitivities for various cancer cells ranges from about -405 RIU-1 to -430 RIU-1, with such a detection limit of 0.025. Keywords—Cancer cells, Cancer Sensing and Detection, Monocore Bowl shaped SPR, Birefringence, and Sensitivity. I. INTRODUCTION The Surface plasmon resonance (SPR) already have shown great promise in the field of sensing. A silicon dioxide core fiber with microscopic round air pockets runs the length of SPR [1]. In order to have more design freedom, We must do an investigation into the FEM using a complete vector software program, COMSOL Multiphysics version 5.1. In biomedical research, though, using SPR-based photonic fiber (PCF), illness monitoring, diagnostics, and detection may be performed to assure better treatment. The very first sensor for sensing glucose from the blood was created by Clark et al. [2]. On a daily basis, new techniques including microfluidic [3], electrolytic [4], phagocytic [5], and cellular cancer detection [6] is being provided. After the growth of separate sites, Yaroslavsky et al. carried out a case study of malignant cancer detection [7], optoelectronic influence on microstructure [8], and body fluids containing malignancy [8], [9]. Sun et al. found a breast cancer biomarker (HER-2) [10]. All following cancer cell detection models, on the other hand, were either based solely on stratum basale with sensitivity levels or less 7000 nmRIU-1 or included sensitivity values for other malignant cell traits. In comparison to normal cells (80% concentration), however, our proposed framework achieves exceptional results in terms of increased sensing in the quick diagnosis of cancer (30–70% concentration). via cell secretions, as shown by our research. Many cancer viruses' internal protein structures vary depending on their optical features, as we all know. The measured values of tumor tissue will also differ. This refractive indices reaction contributes in the differentiation of healthy cells from malignant cells. As a result, the proposed system will be superior to any previously developed model. This article describes an SPRbased optical sensor that can quickly detect cells that have been impacted by malignancy, including leukemia (Jurkat), lymphoma (HeLa), adrenal gland cancer cell (PC12), two types of breast cancer cell (MDA-MB231 and MCF-7) and skin cancer cell (Basal). Furthermore, the percentage of malignant cells in the liquid state is predicted to be around 80%, as well as the detection method is the Finite Element Method (FEM). The suggested D-shaped PCF-SPR malignancy tests were performed at wavelengths spanning from 0.5 to 2.0 µm in order to determine its performance. The purpose is to describe a sensor with increasing wavelength and amplitude sensibility, minimal loss, and good birefringence that is simple to make. The proposed approach will take cancer cell detection to an entirely new level. TABLE I II. EASE OF USE The mono-core transmission modes in a bowl-shaped structure dominate the suggested model's bi-sectional perspective. As a background, a silica arc has been employed and PML as a component. (a) (b) (c) Fig. 1 (a) Bowl shaped proposed fiber design; (b) core mode for x- polarization; (c) core mode for y-polarization A sequence of air holes with widths of r1=500 nm, r2=200 nm, r3=300 nm, and pitch P=2µm restricts the internal lattice structure in the core area, which includes the ring structure shown in Fig. 1, to alter the mode confinement At the bottom of the structure, a single layer of biosample is formed and separated from the silica by a thin Indium Tin oxide (ITO) coating with a thickness of 50 µm. Depending on the size of the air holes; the bio-samples are more or less sensitive. Table I displays the biosamples refractive indices and dielectric constants. Use individually unaffected cells to compare the sensitivity variations of cancerous cells of different types. Additionally, the suggested model is an enhanced PCF in the D-shape with an enlarged form, providing greater optical parameter flexibility and improving sensing performance. The layer of the analyte is connected to the flat section of the "D" in the D-shape SPR PCF. However, in our model, it is connected to the below of "D," which adds steadiness and resilience to the sensing process. This is due to the gap between both the fiber core's center and the metallic layer's interface., the entire core radius can develop properly, resulting in an increase in plasmon. The conventional D-shape, on the other hand, results in a poorly formed core on the analyte side, reducing plasmon. As a consequence, the sensitivity of the reaction will be reduced. Because of its simple design, the suggested sensor may be manufactured using existing technologies such as solgel, extrusion, and drilling techniques. Due to the reliance on surface plasmon incident at the metal-analyte interface, imperfections in the production of air holes have almost no impact on PCF biosensor performance. Air holes, on the other hand, are utilized as a gate for the core mode, which is unrelated to plasmonic incidence. Thus, it should be relevant only to PCF and not to SPR-based PCF. The template is used to format your paper and style the text. All margins, column widths, line spaces, and text fonts are prescribed; please do not alter them. You may note peculiarities. For example, the head margin in this template measures proportionately more than is customary. This measurement and others are deliberate, using specifications that anticipate your paper as one part of the entire proceedings, and not as an independent document. Please do not revise any of the current designations. III. THEORITICAL ANALYSIS The suggested cancer sensor's primary purpose is to discover cancer using the FEM approach and develop plasmonic resonance in order to define the overall change of light absorption by the relevant bio-sample. The wavelength sensitivity(nm/RIU),transmission spectrum, and transmittance variance (dB/RIU) of D-shaped SPR are analyzed from the outcome in different modes of X-polarization and Ypolarization. After calculating the inference of the mono-core structure of the coupling length, the following equations must be used. To divide these modes into two groups, we used the following criteria: The suggested SPR PCF requires deep mode confinement for X-polarization modes (nx) and Y-polarization modes (ny) represented in Fig. 1. (b). According to the Sellmeier's RI equation for fused silica material [20], The suggested model's effective RI may be computed as follows: n ( RIU ) = 1 + B3 2 B1 2 B2 2 + + 2 − C1 2 − C2 2 − C3 (1) Where n is the effective refractive index (RI) of fused-silica and B1=0.696163, B2=0.4079426, B3=0.8974794, C1=0.0046914826 µm2 , C2=0.0135120631 µm2, and C3=97.9340025 µm2 are the Sellmeier’s constants for fused silica, respectively. The D-Shaped SPR-PCF birefringence (B) or refractive index difference between various super modes of X polarization and Y polarization [11], [12] given below: B = nxi − niy (2) Here, i denotes the proposed model's X or Y polarization. For X and Y polarization, Eq. 2 considers the whole range of refractive index differences between various modes with respect to the wavelength. Any plasmonic structure encounters the issue of mode confinement loss (αc), which cannot be eliminated. Concealment-loss is a term that is often used to describe a structure's sensitivity. The suggested model's confinement-loss be estimated as, c ( dB / cm ) = 8.686 2 10 4 (3) Here, lambda (λ) denotes the wavelength that is taken into account for the suggested structure. In general, coupling length refers to the shortest distance at which the most significant quantity of light may easily travel through the tiny silica core. For the D-shaped SPR PCF [11], [12], the coupling length Lc of the mono core in X polarization and Y polarization can be determined by following equation: Lc ( m) = 2 B (4) Where B is the birefringence. We must determine the length of the D-shaped SPR PCF's coupling length cancer sensor for various wavelengths using Eq. (4). The length of the D-shaped SPR PCF coupler is clearly inversely related to the wavelength. The suggested structure allows for an optical field to flow through the mono core, which allows for improved cancer sensing. The optical power output that goes through the silica core is specified to compute the sensing, Pout ( watt ) = sin 2 nx − ny IV. RESULT ANALYSIS AND DISCUSSION (5) The fiber's whole length is denoted by the letter L. As a result, we can use Eq. 5 to calculate the optical power that goes through the mono-core along the proposed PCF with a variable fiber length L. The transmittance spectrum [11], [12] may be examined when light travels through the proposed fiber, P Tr (dB ) = 10 log10 out Pin (6) The maximum power input and output are designated as Pin and Pout, respectively. Nevertheless, it is possible to measure the wavelength sensitivity of the presented sensor by subtracting the total variation in RI from the displacement of the acute zenith of the transmittance curl at destined wavelength. The wavelength sensitivity for density level may be characterized as [13], [11], and [12]. S w ( nm / RIU ) = p n (7) The fluctuation of peak wavelength is denoted by Δλp, while the variation of cancer cell RI is denoted by Δn. Thus, Eq. 7 is used to determine a cancer cell's sensitivity, and the transmittance curve may be adjusted using the transmittance variance or Tr sensitivity. The Refractive Index variation between healthy and cancerous cells is nb, and txb1:txb2 is the maximum amplitude Tr curves for b1 and b2 bio-samples, respectively. However, any difference in the resolution of the suggested structure may readily detect any change in the Refractive Index of the biosamples. As a result, the suggested model's resolution may be assessed by, ( Sv dB (t ) = max max ( n RIU − t xb 2 ) b1 − nb 2 ) xb1 Every figure in this study illustrates the optical features of healthy and cancer-affected cell bio-samples as a function of wavelength. Both the X-axis and Y-axis curves are depicted by the circular and triangular markers, respectively. Figure 2 depicts the RI's reaction to a shift in wavelength. The biosamples refractive index is steadily decreasing, making it clear RI's prepositional curvature features a straight line as well as a linear structure. To begin, the bio-sample has its maximum RI, then falls to its lowest. The total system will be affected linearly if we swap the refractive index for different bio-samples. The highest possible range of RI is 1.46 to 1.47 for biological samples. Figures 3 and 4 show the X-and Y-polarization loss spectra as a function of the wavelength, the spp mode, and the core mode. The junction position between the core guiding mode and the spp directing mode provide the biggest high point result of the maximum confinement loss for every specific cancer or malignant cell bio-sample. This suggested model predicts that cancer cell bio-samples will have a few crossing spots in the X and Y polarizations at wavelengths of 1.2 µm, 1.3 µm, 1.4 µm, 1.5 µm, 1.6 µm, 1.7 µm, and 1.22 µm, 1.34 µm, 1.45 µm, 1.51 µm, 1.67 µm, 1.73 µm, respectively. This is consistent with the results of previous studies. There is also a note stating that this sensor has the best sensitivity in that area. A cancer model based on these confinement loss curves shows X-polarization losses of 467 dBcm-1, 557 dBcm-1, 657 dBcm-1, 840 dBcm-1, 1030 dBcm-1, and 1144 dBcm-1, Y-polarization losses of and 450 dBcm-1, 510 dBcm-1 , 650 dBcm-1, 830 dBcm1 ,1031 dBcm-1, 1176 dBcm-1 respectively. The loss curve, as well as the intersection point of both the core mode and spp mode, define the amplitude sensitivity and mode resolution of the presented cancer sensor (8) Here, ∆n denotes the RI difference, while ∆λmin and ∆λpeak denotes the lowest and maximum wavelength differences, respectively, for that particular Refractive Index of the healthy cells and cancerous or malignant cells for cancer diagnosis. For the matching cancer cells, the values of ∆n are 0.014, 0.024, 0.014, 0.014, 0.014, 0.014 and 0.02, 0.1 nm is the ∆λmin and ∆λpeak are 0.26,0.2,0.18,0.17,0.16,0.14 and 0.19. The phasedetection technique used to manage the amplitude interrogation method is directly affected by the sensor's resolution. The amplitude sensitivity equation may be used to reduce the complexity of the amplitude interrogation approach. The suggested cancer sensor's amplitude sensitivity can be assessed using RI ( RIU ) = n min peak (9) Here, the confinement loss of the individual bio-samples is denoted by αc, while the variation in loss and RI between healthy and malignant cells is denoted by αc and ∆n, respectively. Fig. 5 The loss in mode confinement of Y-polarization vs. wavelength for different types of cancer cells, as well as the SPP mode as well as Core mode at 80% concentration for the proposed structure. Fig. 6 The amplitude sensitivity vs. wavelength for the proposed structure. Bio-samples of malignant cells are shown in Figure 5 in relation to their amplitude sensitivity in terms of wavelength. The suggested model generates a severe negative spike in amplitude sensitivity for every individual malignant cell biosample. As indicated in Table II, the maximum amplitude sensitivity for each associated cancer cell bio-sample is around -405 RIU-1, -407 RIU-1, -412 RIU-1, -420 RIU-1, -425 RIU-1, and -430 RIU-1. The proposed model appears to be more reactive to the amplitude variation of the corresponding malignant cells in biomedical samples, which increases the resolution of the presented cancer sensor. The cancer sensor proposed here has a maximum interrogative resolution of around 7.37×103 RIU, 1.41×102 RIU, 6.67×103 RIU, 9.35×103 RIU, 8.75×103 RIU, and 1.54×102 RIU. Fig. 8 Computed RIU as function of wavelength for x & y polarization of the proposed structure Fig. 9 Calculated coupling length as function of wavelength for the proposed structure Fig. 10 The birefringence response vs. wavelength for the proposed structure Fig. 7 The calculated transmittance vs. wavelength for the proposed structure In this case, the suggested cancer detector sensor may surpass all existing models. As seen in Figure 6, the plasmon's birefringence is critical for bio-sample detection on SPR-based PCF. The maximum practicable birefringence limits between nearly 0.02 and 0.04, showing an upward rising slope, as the birefringence of the proposed structure has a direct effect on its coupling length as well as wavelength sensitivity. In terms of the postulated wavelength fluctuation, it is straightforward to assert that the birefringence of the matched cancer cells behaves linearly along a straight line. The birefringence of the suggested sensor starts at 0.02 and increases linearly with wavelength variation of a high birefringence ending of 0.04. V. DATA TABLE ANALYSIS TABLE I THE REFRACTIVE INDICES FOR JURKAT, HELA, PC12, MBA-MD 231,MCF-7 AND CANCEROUS CELL AS WELL AS THEIR CORRESPONDING NORMAL CELLS Cell Name Jurkat HeLa PC12 MDA-MB-231 MCF-7 Basal Cell type and Concentration Level Blood Cancer (80%) Normal cell (30-70%) Cervical Cancer (80%) Normal cell (30-70%) Adrenal Glands Cancer (80%) Normal cell (30-70%) Breast Cancer (80%) Normal cell (30-70%) Breast Cancer (80%) Normal cell (30-70%) Skin Cancer (80%) Normal cell (30-70%) Refractiv e Index 1.39 1.376 1.392 1.368 1.395' Reference 1.381 1.399 1.385 1.401 1.387 1.38 1.36 [10] - [13] [10] - [13] [10] - [13] [10] - [13] [10] - [13] [12],[13] [12], [13] [10] - [12] [10] - [12] [10] - [13] [10] - [13] [10] - [13] TABLE II THE RELATIVE SENSITIVITY PROFILE FOR JURKAT, HELA, PC12, MBAMD- 231, MCF-7 AND CANCEROUS CELL AS WELL AS THEIR CORRESPONDING NORMAL CELLS Cell Nam e Jurka t HeLa PC12 MDA MB231 MCF -7 Basal Cell & Dens ity Level Blood Cancer (8 0%) Blood Cancer (8 0%) Cervical Cancer (8 0%) Cervical Cancer (8 0%) Adrenal Glan ds Canc er (80%) Adre nal Glan ds Canc er (80% ) (80%) Breast Canc er (80 %) Brea st Canc er (80%) Brea st Canc er (80%) Brea st Canc er (80%) Skin Canc er (80 %) Skin Canc er (80%) Sw(nm /RIU) Sa(R IU-1) RI(RIU) Sv(dB/R IU ) DL 1.11×104 -405 7.37×10-3 5857.14 .014 1.07×104 -330 7×10-3 5357.14 1.04×104 -407 1.41×10-2 3571.42 1.02×104 -304 1.4×10-2 3333.33 1.03×104 -412 6.67×10-3 5500 1.0×104 -375 1×10-2 5357.14 1.8×104 -420 9.35×10-3 6785.71 1.78×104 -380 9.33×10-3 6071.42 1.84×104 -425 8.75×10-3 5714.28 1.81×104 -410 8.75×10-3 5642.85 1.78×104 -435 1.54×10-2 4166.67 1.75×104 -430 15×10-2 3900 .024 .014 .014 .014 .02 The coupling length varies gradually as the wavelength increases in Figure 7. The coupling length varies smoothly (80%) with wavelength variation for normal cells (30–70%) and malignant cells (90–100%). The maximum length of a possible connection ranges between about 35 and 70 µm, showing an upward-curving tendency, as seen in the illustration. Additionally, the proposed model's coupling length has a direct effect on the transmittance. The transmittance of the recommended model reveals the cancer sensor's sensing capabilities. The variation in transmittance as the wavelength of the malignant cell varies is seen in Figure 8. The maximum transmittance is in the middle of -100 and 200 dB, and the pick point for every cell bio sample demonstrates the optimum sensing capability at that place, as seen in the figure. Using equations. (6), (7), and (8) in Table II, the optimal wavelength respondents for blood cancer (Jurkat) is 11071.43 nmRIU-1, cervical cancer (HeLa) is 10416.67 nmRIU-1, adrenal glands cancer(PC12) is 10357.14 nmRIU-1, breast cancer (MDA-MB-231) cell is 18214.28 nmRIU-1, and breast cancer(MCF-7) cell is 18428.57 nmRIU1 and skin cancer (Basal) has a sensitivity of about 17750 nmRIU-1. The fundamental shortcoming of prior models has been that they depended on the activity of adjacent cancer cells to identify a single cancer cell. They compared just one malignant cell's performance to that of another cancerous cell. Therefore, the proposed structure's primary objective is to distinguish various kinds of cancer cell bio-samples from their normal body counterparts. This is the most effective means of detecting cancer. Normal cells (30–70%) and malignant cells (80%) exhibit birefringence in terms of wavelength fluctuation. REFERENCES [1] [2] [3] [4] [5] [6] [7] [8] [9] VI. CONCLUSION A more optimized and enlarged variant of the D-shape PCF is suggested, which has more optical parameter flexibility and enhanced sensitivity over the original model. In terms of wavelength sensing performance, the proposed model outperforms any other current or prior models, with wavelength sensing performance of approximately 11071.43 nmRIU-1, 10416.67 nmRIU-1, 10357.14 nmRIU-1, 18214.28 nmRIU-1, 18428.57 nmRIU-1, and 17750 nmRIU-1 for various polarization modes, transmittance variance of approximately 5857.14 dB/RIU, 3571.42 dB/RIU, 5500 dB/RIU, 6785.71 dB/RIU, 5714.28 dB/RIU, and 4166.67 dB/RIU and amplitude sensitivity is nearly about -405 RIU-1, -407 RIU-1, -412 RIU-1, -420 RIU-1, -425 RIU-1 and -430 RIU-1 with resolution level from 7.37×10-3 RIU to 1.41×10-3 RIU respectively for blood, cervical, adrenal, breast [type-1,2] and skin cancer respectively with a maximum detection limit which is almost 0.02. [10] [11] [12] [13] E. K. Akowuah, H. Ademgil, S. Haxha, and F. AbdelMalek, “An Endlessly Single-Mode Photonic Crystal Fiber With Low Chromatic Dispersion, and Bend and Rotational Insensitivity,” J. Light. Technol., vol. 27, no. 17, pp. 3940–3947, Sep. 2009. L. C. C. Jr, “Implantable gas-containing biosensor and method for measuring an analyte such as glucose,” US4721677A, Jan. 26, 1988 Accessed: May 13, 2022. [Online]. Available: https://patents.google.com/patent/US4721677A/en L. Hajba and A. Guttman, “Circulating tumor-cell detection and capture using microfluidic devices,” TrAC Trends Anal. Chem., vol. 59, pp. 9– 16, Jul. 2014, doi: 10.1016/j.trac.2014.02.017. T. Li, Q. Fan, T. Liu, X. Zhu, J. Zhao, and G. Li, “Detection of breast cancer cells specially and accurately by an electrochemical method,” Biosens. Bioelectron., vol. 25, no. 12, pp. 2686–2689, Aug. 2010, doi: 10.1016/j.bios.2010.05.004. “Detection of circulating tumor cells in breast cancer with a refined immunomagnetic nanoparticle enriched assay and nested-RT-PCR ScienceDirect.” https://www.sciencedirect.com/science/article/abs/pii/S15499634130009 44 (accessed May 13, 2022). T. D. Bradley et al., “Optical Properties of Low Loss (70dB/km) Hypocycloid-Core Kagome Hollow Core Photonic Crystal Fiber for Rb and Cs Based Optical Applications,” J. Light. Technol., vol. 31, no. 16, pp. 2752– 2755, Aug. 2013. “Temperature-insensitive photonic crystal fiber interferometer for absolute strain sensing: Applied Physics Letters: Vol 91, No 9.” https://aip.scitation.org/doi/abs/10.1063/1.2775326 (accessed May 13, 2022). “A paper-based detection method of cancer cells using the photothermaleffect of nanocomposite -ScienceDirect.” https://www.sciencedirect.com/science/article/abs/pii/S07317085153015 88 (accessed May 13, 2022). N. Nallusamy, R. Vasantha Jayakantha Raja, and G. J. Raj, “Highly Sensitive Nonlinear Temperature Sensor Based on Modulational Instability Technique in Liquid Infiltrated Photonic Crystal Fiber,” IEEE Sens. J., vol. 17, no. 12, pp. 3720–3727, Jun. 2017, doi: 10.1109/JSEN.2017.2699186. A. N. Yaroslavsky et al., “High-contrast mapping of basal cell carcinomas,” Opt. Lett., vol. 37, no. 4, pp. 644–646, Feb. 2012, doi: 10.1364/OL.37.000644. N. Ayyanar, G. Thavasi Raja, M. Sharma, and D. Sriram Kumar, “Photonic Crystal Fiber-Based Refractive Index Sensor for Early Detection of Cancer,” IEEE Sens. J., vol. 18, no. 17, pp. 7093–7099, Sep. 2018, doi: 10.1109/JSEN.2018.2854375. P. Sharan, S. M. Bharadwaj, F. Dackson Gudagunti, and P. Deshmukh, “Design and modelling of photonic sensor for cancer cell detection,” in 2014 International Conference on the IMpact of E-Technology on US (IMPETUS), Jan. 2014, pp. 20–24. doi: 10.1109/IMPETUS.2014.6775872. K. Ahmed et al., “Refractive Index-Based Blood Components Sensing in Terahertz Spectrum,” IEEE Sens. J., vol. 19, no. 9, pp. 3368–3375, May 2019, doi: 10.1109/JSEN.2019.2895166.