Development of a MEMS-Based Biosensor for Analyzing the Bio-Electrical Characteristics of Colon Cancer Cells

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Abstract Investigating the bioelectrical characteristics of individual cells can provide important information about many aspects of cellular processes and their roles in general health and disease conditions. Comprehending these attributes at the cellular level facilitates a more intricate comprehension of physiological mechanisms and creates novel opportunities for disease detection, management, and even averting. It's fascinating to observe how new methods and technological developments are allowing us to learn more about the intricacies of cellular biology and how they relate to human health. Since cancer cells have slightly lower capacitance and resistance values, the bioelectrical properties could be used as biomarkers for early cancer identification. Measurements were conducted on the capacitance and resistance of individual normal cell lines (IEC-6), and highly-invasive malignant (SW480) colon cancer cells using MEMS sensors during simulations. Normal cell resistance is 318kΩ, while normal cell capacitance is 8.12nF. These values differ from those of cancer cells, which have variable resistance and capacitance values (246kΩ and 3.91nF for SW480). At a frequency range of 200 Hz to 2 MHz significant difference is observed in impedance magnitude response values between normal cells (7.7 MΩ to 62kΩ) and cancer cells (7.1 MΩ to 54.9kΩ).
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Development of a MEMS-Based Biosensor for Analyzing the Bio-Electrical Characteristics of Colon Cancer Cells | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Development of a MEMS-Based Biosensor for Analyzing the Bio-Electrical Characteristics of Colon Cancer Cells Syed shameem This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4217196/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Investigating the bioelectrical characteristics of individual cells can provide important information about many aspects of cellular processes and their roles in general health and disease conditions. Comprehending these attributes at the cellular level facilitates a more intricate comprehension of physiological mechanisms and creates novel opportunities for disease detection, management, and even averting. It's fascinating to observe how new methods and technological developments are allowing us to learn more about the intricacies of cellular biology and how they relate to human health. Since cancer cells have slightly lower capacitance and resistance values, the bioelectrical properties could be used as biomarkers for early cancer identification. Measurements were conducted on the capacitance and resistance of individual normal cell lines (IEC-6), and highly-invasive malignant (SW480) colon cancer cells using MEMS sensors during simulations. Normal cell resistance is 318kΩ, while normal cell capacitance is 8.12nF. These values differ from those of cancer cells, which have variable resistance and capacitance values (246kΩ and 3.91nF for SW480). At a frequency range of 200 Hz to 2 MHz significant difference is observed in impedance magnitude response values between normal cells (7.7 MΩ to 62kΩ) and cancer cells (7.1 MΩ to 54.9kΩ). MEMS Resistance capacitance Colorectal Cancer conductivity permittivity Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 I. INTRODUCTION This paper outlines the rapidly expanding, evolving area of research that addresses cancer cell biomechanics. Tumor cells change their electrical properties during cancer development, including their resistance and capacitance, which may lead to their altered electrical response. These electrical characteristics are critical to understanding how cells lose memory to do specific functions & forget apoptosis. The importance of cell electrical characteristics in cancer spread is becoming increasingly apparent as our knowledge of cancer research expands. Nevertheless, the advancement in comprehension is not keeping pace with the actual implementation of these methods. Electrical and morphologic screening of cell characteristics provides useful information for differentiating between cell kinds and stages. Numerous techniques have been used to investigate the bioelectric characteristics of individual cells. As label-free diagnostic indicators for the development and course of cancer, these bioelectric properties show promise [4, 5]. However, when working with a large number of cells, it becomes difficult to focus on the unique bioelectric properties of each individual cell [6]. As a result, there is growing interest in microfluidic-based methods, which present extremely precise chances for single-cell screening [7–10].Utilizing label-free analysis, we introduced a method for screening individual cells. A single cell can be captured by the device and mechanically stimulated, as demonstrated by cell contraction. Comprehensive study of individual cells at multiple levels is made possible by accurate electrical stimulation and real-time data [11]. Morphological changes that impact electrical parameters are also linked to the transition from normal to malignant states, in addition to changes in physiological and biochemical features. This methodology makes it easier to identify and differentiate between diverse electrical patterns that are exclusive to cancerous and normal cells. Furthermore, there is evidence from multiple studies that changes in cell membrane properties are associated with malignancy, indicating that differences in cell diameter may or may not occur in tandem with changes in electrical properties. [12]. It is imperative to incorporate biosensor components into a device that can load samples and reagents simultaneously and detect signals in an automated format called lab-on-a-chip (LOC) [13]. In an effort to find new paths for improving diagnosis and treatment, this study explores the relationship between sensor research, technology, and a number of high-mortality malignancies (including colorectal, prostate, breast, and lung cancers). The results emphasise the critical role that biosensors and electrochemical biosensors play in the study of prostate, lung, and breast cancers, but not colorectal cancers [14]. Research on prostate, lung, and breast cancers uses electrochemical biosensors; however, colorectal cancers do not. This work highlights the great promise of wearable microfluidics and microfluidics in the biomedical domain, especially in continuous health monitoring, diagnosis, and treatment. It highlights notable research projects that use 2D materials for sensing in various environmental and healthcare fields. Electrochemical biosensors stand out among wearable biosensors as important players in sensing technology [15]. Microfluidic cytometry (MC) and electrical impedance spectroscopy (EIS) are two methods that are particularly important in the field of biomedical engineering. Numerous domains, including as stem cell differentiation and cancer metastasis investigations, use microfluidic cytometry. It provides an easy-to-use, label-free, real-time method for tracking and characterising cell fates [16]. Microfluidic devices can identify a variety of cancer-related indicators found in biological fluids and can also be used to create customized nanoparticles for medication administration. As such, their application has great potential in cancer research field because of their exceptional sensitivity, throughput, and affordability. Microfluidic systems are expected to become the main technology for cancer diagnosis and therapy, even if they haven't yet entered clinical use. The unique electrical, optical, and structural characteristics of electrochemical biosensors and nanomaterials, along with their biocompatibility, make them unique for use in the development of peptide-based microfluidic biosensors. There is a lot of promise in this method for finding circulating tumor cells (CTCs) [17]. In a traditional label-free biosensor configuration, signals are transformed into optical, mechanical, or electrical forms for sensing, which provides increased accuracy because biorecognition systems are involved directly. In biomedical research, label-free electrochemical biosensors are especially important. Through direct electron transfer between the electrode surface and biorecognition components, which is facilitated by the interaction between biomolecules and analytes, information from reactions is converted into electrical signals within these electrochemical biosensors [18]. For the purpose of medical treatment, diagnostics, and other biological applications, biosensor systems that analyse and characterise particles according to their intrinsic dielectric characteristics are crucial [19]. II. BIO ELECTICAL CHARACTERIZATION Due to changes in the cytoskeletal structure of the cells ther will be changes in the electric/dielectric properties of the cells. The changes in composition of the cytoplasm during tumorigenesis provide a major avenue for identifying cancer cells. One major obstacle to the accurate analysis of single cancer cells is capturing individual cancer cells within a population of cancer cells with different potential for metastasis, or within a mixture of noncancerous cells, like in a blood sample. Using microscale dielectrophoretic forces in lab-on-a-chip (LOC) platforms is one new approach that is starting to show promise in physically manipulating cancer cells. [20]. The electrical impedance is another parameter used to characterize biophysically cancer cells at the single-cell levels. EIS relies on capturing cells between a pair of electrodes with an applied potential and measuring the impedance at various frequencies. The measurement at different frequencies allows for deciphering the capacitive components from the conductive components [21]. Measuring impedance turns out to be a powerful method for evaluating cells according to their electrical behavior in particular frequency bands. It becomes clear that electrochemical impedance spectroscopy (EIS) is a useful method for identifying and evaluating cancer cells. A microfluidic instrument designed for single-cell impedance measurements is presented in this study. Utilizing cell impedance measurement for single-cell analysis provides thorough insights into each individual cell's electrical properties and pathological state. This approach has remarkable diagnostic potential because of how quickly and precisely it can define cellular physiology. Moreover, single-cell impedance is a promising tool for studying the effects of drugs, bacterial and viral infections, environmental conditions, and toxicity, among other things. The examination of single cells has been made significantly easier by the development of micro-electro-mechanical systems (MEMS) technology [22]. Analysis of Cell-Impedance: Fig. 1 shows the circuit model of a cancer cell. It consists of a membrane and a nucleus. The symbols Rm and Cm indicates the resistance and capacitance of the membrane. There is frequency dependence in the impedance response of the parallel combination of Cm and Rm. The total impedance of the cell suspension includes both the impedance provided by the cells and the resistance of the buffer, R b . In addition to the strictly resistive behavior of the buffer, the cell component adds frequency-dependent properties. This cell component consists of the intracellular resistance (Ri) in series with the membrane resistance (Rm) and the membrane capacitance (Cm) in parallel [23]. To distinguish between healthy and malignant cells, we have presented a microchamber array that measures cell impedance. The top layer, which creates a safe contact between the cells and the electrodes inside each microchamber, is an essential component. In contrast to earlier devices, our new configuration only requires loading the cells onto the electrodes inside each microchamber and covering the layer to ensure extended cell-to-electrode contact. Without the need for additional equipment, this design makes frequency-dependent impedance analysis easier. Impedance equation of the cell is Impedance measurement equation of the module is III. PROPOSED MODEL’S WORKING PRINCIPLE Figure 1 illustrates an overview of the setup [5, 24]. For analyzing single-cell’s bioelectrical properties we have proposed a “non-invasive bio-sensor” [25-28]. To measure its electrical properties, the prepared cell is placed in a restricted zone. Applying force to the PDMS layer that covers the confined area causes deformation. Through simulation, the shape of cell deformation was determined. The cross-sectional dimensions of the model in this study were 30 µm × 30 µm x 15 µm. To guarantee solid connections between the cell and electrode, a single-cell is first seeded into each microchamber. Next, as shown in Fig. 2(a), a PDMS cover is placed atop the microchamber array. Next, a simulator was used to measure frequency-dependent electrical signals. A set of electrodes is placed on the glass substrate in the microchamber (Fig. 2c) to position individual cells. A PDMS cover is placed on top to create contact between the electrode and cell [24]. Improving the working electrode's surface area expands the region that can be used to immobilize the probe and speeds up electron transport at the electrode interface [29]. Each micro chamber’s volume is 30 × 30 × 15 μm 3 such that a single isolated cell could be trapped by the PDMS cover. The diameter of the contact region between the electrode and the cell is approximately 80% of the single-cell diameter, which is about 18μm. To take the signal analysis a gap of 5μm is taken between the electrodes. Thus, each electrode’s exposed area 13.5μm long and 18μm wide in a single chamber. The Electrode chamber Top-view is visible in Fig. 2(b). The electrode chamber’s dimensions of are shown in Table 1. For measuring the electrical property of the cell, a trap structure design is modeled using (COMSOL 5.3) F.E.M. tool. The structure is modeled in MEMS to estimate the bio electrical properties of cells [30-35]. The E.I.S. approach has been used by many researchers to classify and identify malignant cells [24]. Increased permeability is the result of cancerization-induced membrane deterioration in both cells and mitochondria. As a result, in malignant cells, different ions can pass across these membranes [37]. Studies show that aberrant cells whether malignant or bacterially infected display different electrical properties from non cancerous cells because of alterations in ion channel activity or cytoplasmic content [25, 36]. Furthermore, the electrical characteristics of normal and malignant cells are affected by differences in their lipid compositions [38]. Cell electrical characteristics therefore have great potential as a critical marker for early cancer identification. The flow control problems make attaining single-cell loading difficult. Furthermore, the current techniques do not allow enough time for the best possible cell-to-electrode contact, which results in imprecise frequency-dependent impedance responses. As a result, obtaining frequency-dependent data requires multiple repeated experiments because each frequency level's attributes must be obtained separately. Many strategies have been tried to promote cell-electrode interaction, including the use of pneumatic membranes, the formation of augmented pillar structures, and the application of additional electric signals. However, these techniques require intricate sample controls in order to place cells on electrodes, and it is still difficult to make accurate contact with individual cells. Alternative approaches, such as cell capture structures, dielectrophoresis (D.E.P.) forces, and cell impedance analysis chips constrained by membranes under external pressures, have been proposed to solve these issues. The chip places individual cells on electrodes inside each microchamber to guarantee a sufficient amount of time for cell-to-electrode contact. This is accomplished by applying polydimethylsiloxane (PDMS) to the top layer, which allows frequency-dependent analysis of single-cell impedance to be performed without the requirement of additional equipment. In addition to differentiating cells according to their electrical properties, this impedance analysis structure makes it possible to measure each cell's electrical characteristics precisely, which enables sophisticated cellular analysis like cancer diagnosis. IV. RESULTS AND DISCUSSION Fig.4 to Fig.7 shows the simulation results of electrical parameters measurements. In the frequency range of 25 kHz to 1.67 MHz, IEC-6 cells showed greater impedance magnitudes (60.07–154.36kΩ) than human colon cancer cells (SW480). Cellular components such physiological conditions, membrane characteristics, and cytosolic features are probably responsible for these variances in impedance response [39, 40]. When one cell is exposed to an electric field, there are detectable changes in the typical impedance signature of the cell, which are explained by localized distortions in the field. This makes it possible to classify normal cell types and identify aberrant cells. Normal cells have resistance and capacitance values of 318kΩ and 8.12nF, respectively. These values are very different from those of cancer cells, which have values of 246kΩ and 3.91nF for SW480. It was determined that cancer cells had an average resistance of 255kΩ and an average capacitance of 3.53nF. It is noteworthy that the electrical parameter values for malignant tumor cells and SW480 cancer cells are within the same range. Furthermore, we noticed variations in electrical disruption values that correlated with the grades of cancer metastasis. Analysis of Cell impedance Under optimal conditions, the impedance magnitude responses of IEC-6 normal colon cells and SW480 human colorectal cancer cells were measured and compared within the 200 Hz–1.67 MHz frequency range using a 200 mVp-p AC signal. The observed differences in impedance magnitude between malignant and non-cancerous cells are shown in Fig. 8. Significant variations in response magnitude were observed, indicating significant differentiation between cancerous and normal cells. Increasing the frequency can cause variations in the membrane potential of cells due to electromagnetic fields. As such, the electrical characteristics of cancer cells may be altered by high-frequency electrical currents. This change frequently appears as a decrease in the resistance and capacitance values inside the cells, which eventually results in a decrease in the magnitude of the cell impedance. This effect is demonstrated in Figure 8, which shows the reduced impedance values found in both malignant and non-cancerous cells. In order to facilitate frequency-dependent single-cell impedance analysis, this study presents a simple microchamber array for impedance measurement. A PDMS cover maintains uniform cell-to-electrode connections within each microchamber. By adjusting cell concentrations and measuring cell-to-electrode contact rates, we used simulation to verify single-cell entrapment and contact stability. IEC-6 cells showed greater impedance magnitudes (60.07–154.36kΩ) in the 95.6 kHz–2 MHz frequency range when compared to SW-480 human colon cancer cells in the impedance analysis. Furthermore, in the frequency range of 4.37 kHz to 2 MHz, IEC-6 cells showed greater impedance phases (3.96–20.80°) than human colon cancer cells. As a result, compared to CCD-18 cell lines (271kΩ and 7.01nF), cancer cells showed reduced resistance and capacitance (241kΩ and 3.13nF), showing clear distinctions between healthy and malignant colon cells. Our microchamber array demonstrated consistent cell-to-electrode contact and effective single-cell loading, which made it easier to distinguish between cancerous and healthy cells. This process provides a viable method for describing the characteristics of cancer cells. V. CONCLUSION In order to facilitate the evaluation of single-cell electrical properties, this work offers a microchamber array that is intended for simple measurement of capacitance and resistance. Each microchamber is equipped with a PDMS cover that guarantees robust cell-to-electrode connections. The method for determining each cell's unique organic electrical characteristics is described in this paper. Because of the high sensitivity of our model, we can precisely identify changes in the electrical characteristics of cells. Our study combines microfluidics' high-throughput capabilities with sensitive microelectromechanical systems (MEMS) technology measurements to carry out biophysical characterization of circulating cells for diagnostic purposes. SW480 human colon cancer cells showed lower resistance levels in the electrical investigation than did IEC-6 cells. As thus, compared to normal colon cells (271kΩ and 7.01nF), cancer cells showed reduced resistance and capacitance values (241kΩ and 3.13nF). At a frequency of 50 KHz significant difference is observed between normal cells (700kΩ) and cancer cells (608kΩ) in magnitude response. We demonstrated by simulation that the microchamber array may be used to discriminate between normal and cancerous cells by facilitating straightforward single-cell loading and preserving stable cell-to-electrode connections. Declarations Funding This work is not funded by any organization. Facilities were provided by MEMS Lab, KL University Acknowledgment We acknowledge that a portion of our research was conducted using the facilities at the MEMS Lab, KLEF. References Mohajerzadeh, Single-cell resolution diagnosis of cancer cells by carbon nanotube electrical spectroscopy, Nanoscale, The Royal Society of Chemistry 2013, DOI: 10.1039/c3nr33430a Grossi and B. Riccò: E.I.S. for biological analysis and food characterization, J. Sens. Sens. Syst., 6, 303–325, 2017. Hyeon Woo Kim, Differentiation Between Normal and Cancerous Human Urothelial Cell Lines Using Micro‑Electrical Impedance Spectroscopy at Multiple Frequencies, Journal of Medical and Biological Engineering, 2018. Robert Langer, Design and Testing of an Impedance-Based Sensor for Monitoring Drug Delivery, Journal of The Electrochemical Society, 152 ~1! H6-H11 ~2005! Suresh S. Biomechanics and biophysics of cancer cells. 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Tables TABLE I. electrode chamber :Measurements Elements Symbol Dimensions[μm] Chamber width L 40 Chamber height Hc 16 Electrode gap G 5 Electrode width W1 15 W2 30 Electrode height He 2000(A) Table 2 Impedance magnitude values of normal colon cell & cancer cell Frequency(Hz) Non-cancer Impedance magnitude(Ω) Cancer Impedance magnitude(Ω) 200 7682215 7110450 10000 2360265 1984051 50000 700000 608000 250000 205000 132000 466820 155000 87200 666800 95000 83000 800120 88510 71600 1066760 75800 64800 1200080 70000 58360 1400060 66300 57200 1666700 62000 54900 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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10:23:23","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4217196/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4217196/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":55001944,"identity":"fb946ed1-0b9b-405e-9f81-7ab07050d09d","added_by":"auto","created_at":"2024-04-19 18:38:55","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":7333,"visible":true,"origin":"","legend":"\u003cp\u003eCell inside the chamber: Equivalent circuit model [23] .\u003c/p\u003e","description":"","filename":"Picture1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4217196/v1/5f7d91e5db3180c5984b4a2a.jpg"},{"id":54998203,"identity":"0b638207-09e4-4c70-b3d3-4bb38ad8ef0a","added_by":"auto","created_at":"2024-04-19 18:22:55","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":101593,"visible":true,"origin":"","legend":"\u003cp\u003e(a) Placement of cell in the model chamber, (b) Electrode chamber Top-view and (c) Electrode-chamber\u003c/p\u003e","description":"","filename":"F2.png","url":"https://assets-eu.researchsquare.com/files/rs-4217196/v1/f66e880457e1023d2518554c.png"},{"id":54999716,"identity":"007fb8c2-219a-4f0d-9666-c8dc00b7cc35","added_by":"auto","created_at":"2024-04-19 18:30:55","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":15750,"visible":true,"origin":"","legend":"\u003cp\u003eCell trap Design structure in F.E.M. tool\u003c/p\u003e","description":"","filename":"Picture2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4217196/v1/7a72405185888ca598865ccd.jpg"},{"id":55001943,"identity":"cbbcaf32-0e04-4b0c-938a-6509047833c2","added_by":"auto","created_at":"2024-04-19 18:38:55","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":21227,"visible":true,"origin":"","legend":"\u003cp\u003eElectrical parameters measurement at 200Hz.\u003c/p\u003e","description":"","filename":"Picture3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4217196/v1/b9ff21ddddb7c5470723b55f.jpg"},{"id":54999713,"identity":"7c54b051-2cc4-42af-92c3-6f1dd36df9bc","added_by":"auto","created_at":"2024-04-19 18:30:55","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":16617,"visible":true,"origin":"","legend":"\u003cp\u003eElectrical parameters measurement at 10kHz.\u003c/p\u003e","description":"","filename":"Picture4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4217196/v1/c09e2ec974110d0477a8c5ff.jpg"},{"id":54998208,"identity":"aa289472-1626-4aec-bc37-cbd0e3a3a70f","added_by":"auto","created_at":"2024-04-19 18:22:55","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":15985,"visible":true,"origin":"","legend":"\u003cp\u003eElectrical parameters measurement at 1.06MHz.\u003c/p\u003e","description":"","filename":"Picture5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4217196/v1/97108375ec81219ab1e824a8.jpg"},{"id":54998209,"identity":"5f5d679b-4acd-494f-95ab-21a65d67f8b0","added_by":"auto","created_at":"2024-04-19 18:22:55","extension":"jpg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":16701,"visible":true,"origin":"","legend":"\u003cp\u003eElectrical parameters measurement at 2MHz.\u003c/p\u003e","description":"","filename":"Picture6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4217196/v1/1b0283790cc4d51336f2c820.jpg"},{"id":54999717,"identity":"22dce5d7-7f86-445d-be9e-4c96db374ea3","added_by":"auto","created_at":"2024-04-19 18:30:55","extension":"jpg","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":23149,"visible":true,"origin":"","legend":"\u003cp\u003eMagnitude (Impedance) response of cells: Normal (Non-Cancerous) Vs Cancerous\u003c/p\u003e","description":"","filename":"Picture7.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4217196/v1/ce469813ca02838bf5a5430d.jpg"},{"id":56437606,"identity":"9cf0e171-6ec9-489f-b9c8-f6b3aa0b5c76","added_by":"auto","created_at":"2024-05-14 07:45:01","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":512153,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4217196/v1/9ff6301e-fd45-4665-9122-9ed6b4bd39a1.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Development of a MEMS-Based Biosensor for Analyzing the Bio-Electrical Characteristics of Colon Cancer Cells","fulltext":[{"header":"I.\tINTRODUCTION","content":"\u003cp\u003eThis paper outlines the rapidly expanding, evolving area of research that addresses cancer cell biomechanics. Tumor cells change their electrical properties during cancer development, including their resistance and capacitance, which may lead to their altered electrical response. These electrical characteristics are critical to understanding how cells lose memory to do specific functions \u0026amp; forget apoptosis.\u0026nbsp;The importance of cell electrical characteristics in cancer spread is becoming increasingly apparent as our knowledge of cancer research expands. Nevertheless, the advancement in comprehension is not keeping pace with the actual implementation of these methods. Electrical and morphologic screening of cell characteristics provides useful information for differentiating between cell kinds and stages. Numerous techniques have been used to investigate the bioelectric characteristics of individual cells. As label-free diagnostic indicators for the development and course of cancer, these bioelectric properties show promise [4, 5]. However, when working with a large number of cells, it becomes difficult to focus on the unique bioelectric properties of each individual cell [6]. As a result, there is growing interest in microfluidic-based methods, which present extremely precise chances for single-cell screening [7\u0026ndash;10].Utilizing label-free analysis, we introduced a method for screening individual cells. A single cell can be captured by the device and mechanically stimulated, as demonstrated by cell contraction. Comprehensive study of individual cells at multiple levels is made possible by accurate electrical stimulation and real-time data [11].\u003c/p\u003e\n\u003cp\u003eMorphological changes that impact electrical parameters are also linked to the transition from normal to malignant states, in addition to changes in physiological and biochemical features. This methodology makes it easier to identify and differentiate between diverse electrical patterns that are exclusive to cancerous and normal cells. Furthermore, there is evidence from multiple studies that changes in cell membrane properties are associated with malignancy, indicating that differences in cell diameter may or may not occur in tandem with changes in electrical properties. [12].\u003c/p\u003e\n\u003cp\u003eIt is imperative to incorporate biosensor components into a device that can load samples and reagents simultaneously and detect signals in an automated format called lab-on-a-chip (LOC) [13]. In an effort to find new paths for improving diagnosis and treatment, this study explores the relationship between sensor research, technology, and a number of high-mortality malignancies (including colorectal, prostate, breast, and lung cancers). The results emphasise the critical role that biosensors and electrochemical biosensors play in the study of prostate, lung, and breast cancers, but not colorectal cancers [14]. Research on prostate, lung, and breast cancers uses electrochemical biosensors; however, colorectal cancers do not.\u003c/p\u003e\n\u003cp\u003eThis work highlights the great promise of wearable microfluidics and microfluidics in the biomedical domain, especially in continuous health monitoring, diagnosis, and treatment. It highlights notable research projects that use 2D materials for sensing in various environmental and healthcare fields. Electrochemical biosensors stand out among wearable biosensors as important players in sensing technology [15].\u003c/p\u003e\n\u003cp\u003eMicrofluidic cytometry (MC) and electrical impedance spectroscopy (EIS) are two methods that are particularly important in the field of biomedical engineering. Numerous domains, including as stem cell differentiation and cancer metastasis investigations, use microfluidic cytometry. It provides an easy-to-use, label-free, real-time method for tracking and characterising cell fates [16].\u003c/p\u003e\n\u003cp\u003eMicrofluidic devices can identify a variety of cancer-related indicators found in biological fluids and can also be used to create customized nanoparticles for medication administration. As such, their application has great potential in cancer research field because of their exceptional sensitivity, throughput, and affordability. Microfluidic systems are expected to become the main technology for cancer diagnosis and therapy, even if they haven\u0026apos;t yet entered clinical use. The unique electrical, optical, and structural characteristics of electrochemical biosensors and nanomaterials, along with their biocompatibility, make them unique for use in the development of peptide-based microfluidic biosensors. There is a lot of promise in this method for finding circulating tumor cells (CTCs) [17].\u003c/p\u003e\n\u003cp\u003eIn a traditional label-free biosensor configuration, signals are transformed into optical, mechanical, or electrical forms for sensing, which provides increased accuracy because biorecognition systems are involved directly. In biomedical research, label-free electrochemical biosensors are especially important. Through direct electron transfer between the electrode surface and biorecognition components, which is facilitated by the interaction between biomolecules and analytes, information from reactions is converted into electrical signals within these electrochemical biosensors [18].\u003c/p\u003e\n\u003cp\u003eFor the purpose of medical treatment, diagnostics, and other biological applications, biosensor systems that analyse and characterise particles according to their intrinsic dielectric characteristics are crucial [19].\u003c/p\u003e"},{"header":"II.\tBIO ELECTICAL CHARACTERIZATION","content":"\u003cp\u003eDue to changes in the cytoskeletal structure of the cells ther will be changes in the electric/dielectric properties of the cells. The changes in composition of the cytoplasm during tumorigenesis provide a major avenue for identifying cancer cells. One major obstacle to the accurate analysis of single cancer cells is capturing individual cancer cells within a population of cancer cells with different potential for metastasis, or within a mixture of noncancerous cells, like in a blood sample. Using microscale dielectrophoretic forces in lab-on-a-chip (LOC) platforms is one new approach that is starting to show promise in physically manipulating cancer cells. [20].\u003c/p\u003e\n\u003cp\u003eThe electrical impedance is another parameter used to characterize biophysically cancer cells at the single-cell levels. EIS relies on capturing cells between a pair of electrodes with an applied potential and measuring the impedance at various frequencies. The measurement at different frequencies allows for deciphering the capacitive components from the conductive components [21].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMeasuring impedance turns out to be a powerful method for evaluating cells according to their electrical behavior in particular frequency bands. It becomes clear that electrochemical impedance spectroscopy (EIS) is a useful method for identifying and evaluating cancer cells. A microfluidic instrument designed for single-cell impedance measurements is presented in this study. Utilizing cell impedance measurement for single-cell analysis provides thorough insights into each individual cell\u0026apos;s electrical properties and pathological state. This approach has remarkable diagnostic potential because of how quickly and precisely it can define cellular physiology. Moreover, single-cell impedance is a promising tool for studying the effects of drugs, bacterial and viral infections, environmental conditions, and toxicity, among other things. The examination of single cells has been made significantly easier by the development of micro-electro-mechanical systems (MEMS) technology [22].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAnalysis of Cell-Impedance:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFig. 1 shows the circuit model of a cancer cell. It consists of a membrane and a nucleus. The symbols Rm and Cm indicates the resistance and capacitance of the membrane. There is frequency dependence in the impedance response of the parallel combination of Cm and Rm. The total impedance of the cell suspension includes both the impedance provided by the cells and the resistance of the buffer, R\u003csub\u003eb\u003c/sub\u003e. In addition to the strictly resistive behavior of the buffer, the cell component adds frequency-dependent properties. This cell component consists of the intracellular resistance (Ri) in series with the membrane resistance (Rm) and the membrane capacitance (Cm) in parallel [23]. \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTo distinguish between healthy and malignant cells, we have presented a microchamber array that measures cell impedance. The top layer, which creates a safe contact between the cells and the electrodes inside each microchamber, is an essential component. In contrast to earlier devices, our new configuration only requires loading the cells onto the electrodes inside each microchamber and covering the layer to ensure extended cell-to-electrode contact. Without the need for additional equipment, this design makes frequency-dependent impedance analysis easier.\u003c/p\u003e\n\u003cp\u003eImpedance equation of the cell is\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cimg src=\"data:image/png;base64,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\"\u003e\u003c/p\u003e\n\u003cp\u003eImpedance measurement equation of the module is\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cimg src=\"data:image/png;base64,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\"\u003e\u003c/p\u003e"},{"header":"III.\tPROPOSED MODEL’S WORKING PRINCIPLE ","content":"\u003cp\u003eFigure 1 illustrates an overview of the setup [5, 24]. For analyzing single-cell\u0026rsquo;s bioelectrical properties we have proposed a \u0026ldquo;non-invasive bio-sensor\u0026rdquo; [25-28]. To measure its electrical properties, the prepared cell is placed in a restricted zone. Applying force to the PDMS layer that covers the confined area causes deformation. Through simulation, the shape of cell deformation was determined. The cross-sectional dimensions of the model in this study were 30 \u0026micro;m \u0026times; 30 \u0026micro;m x 15 \u0026micro;m.\u003c/p\u003e\n\u003cp\u003eTo guarantee solid connections between the cell and electrode, a single-cell is first seeded into each microchamber. Next, as shown in Fig. 2(a), a PDMS cover is placed atop the microchamber array. Next, a simulator was used to measure frequency-dependent electrical signals. A set of electrodes is placed on the glass substrate in the microchamber (Fig. 2c) to position individual cells. A PDMS cover is placed on top to create contact between the electrode and cell [24]. Improving the working electrode\u0026apos;s surface area expands the region that can be used to immobilize the probe and speeds up electron transport at the electrode interface [29].\u003c/p\u003e\n\u003cp\u003eEach micro chamber\u0026rsquo;s volume is 30 \u0026times; 30 \u0026times; 15 \u0026mu;m\u003csup\u003e3\u003c/sup\u003e such that a single isolated cell could be trapped by the PDMS cover. The diameter of the contact region between the electrode and the cell is approximately 80% of the single-cell diameter, which is about 18\u0026mu;m. To take the signal analysis a gap of 5\u0026mu;m is taken between the electrodes. Thus, each electrode\u0026rsquo;s exposed area 13.5\u0026mu;m long and 18\u0026mu;m wide in a single chamber. The Electrode chamber Top-view is visible in Fig. 2(b). The electrode chamber\u0026rsquo;s dimensions of are shown in Table 1.\u003c/p\u003e\n\u003cp\u003eFor measuring the electrical property of the cell, a trap structure design is modeled using (COMSOL 5.3) F.E.M. tool. The structure is modeled in MEMS to estimate the bio electrical properties of cells [30-35].\u003c/p\u003e\n\u003cp\u003eThe E.I.S. approach has been used by many researchers to classify and identify malignant cells [24]. Increased permeability is the result of cancerization-induced membrane deterioration in both cells and mitochondria. As a result, in malignant cells, different ions can pass across these membranes [37]. Studies show that aberrant cells whether malignant or bacterially infected display different electrical properties from non cancerous cells because of alterations in ion channel activity or cytoplasmic content [25, 36]. Furthermore, the electrical characteristics of normal and malignant cells are affected by differences in their lipid compositions [38]. Cell electrical characteristics therefore have great potential as a critical marker for early cancer identification.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe flow control problems make attaining single-cell loading difficult. Furthermore, the current techniques do not allow enough time for the best possible cell-to-electrode contact, which results in imprecise frequency-dependent impedance responses. As a result, obtaining frequency-dependent data requires multiple repeated experiments because each frequency level\u0026apos;s attributes must be obtained separately. Many strategies have been tried to promote cell-electrode interaction, including the use of pneumatic membranes, the formation of augmented pillar structures, and the application of additional electric signals. However, these techniques require intricate sample controls in order to place cells on electrodes, and it is still difficult to make accurate contact with individual cells. Alternative approaches, such as cell capture structures, dielectrophoresis (D.E.P.) forces, and cell impedance analysis chips constrained by membranes under external pressures, have been proposed to solve these issues.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe chip places individual cells on electrodes inside each microchamber to guarantee a sufficient amount of time for cell-to-electrode contact. This is accomplished by applying polydimethylsiloxane (PDMS) to the top layer, which allows frequency-dependent analysis of single-cell impedance to be performed without the requirement of additional equipment. In addition to differentiating cells according to their electrical properties, this impedance analysis structure makes it possible to measure each cell\u0026apos;s electrical characteristics precisely, which enables sophisticated cellular analysis like cancer diagnosis.\u003c/p\u003e"},{"header":"IV.\tRESULTS AND DISCUSSION","content":"\u003cp\u003eFig.4 to Fig.7 shows the simulation results of electrical parameters measurements. In the frequency range of 25 kHz to 1.67 MHz, IEC-6 cells showed greater impedance magnitudes (60.07\u0026ndash;154.36k\u0026Omega;) than human colon cancer cells (SW480). Cellular components such physiological conditions, membrane characteristics, and cytosolic features are probably responsible for these variances in impedance response [39, 40].\u003c/p\u003e\n\u003cp\u003eWhen one cell is exposed to an electric field, there are detectable changes in the typical impedance signature of the cell, which are explained by localized distortions in the field. This makes it possible to classify normal cell types and identify aberrant cells. Normal cells have resistance and capacitance values of 318k\u0026Omega; and 8.12nF, respectively. These values are very different from those of cancer cells, which have values of 246k\u0026Omega; and 3.91nF for SW480. It was determined that cancer cells had an average resistance of 255k\u0026Omega; and an average capacitance of 3.53nF. It is noteworthy that the electrical parameter values for malignant tumor cells and SW480 cancer cells are within the same range. Furthermore, we noticed variations in electrical disruption values that correlated with the grades of cancer metastasis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAnalysis of Cell impedance\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eUnder optimal conditions, the impedance magnitude responses of IEC-6 normal colon cells and SW480 human colorectal cancer cells were measured and compared within the 200 Hz\u0026ndash;1.67 MHz frequency range using a 200 mVp-p AC signal. The observed differences in impedance magnitude between malignant and non-cancerous cells are shown in Fig. 8. Significant variations in response magnitude were observed, indicating significant differentiation between cancerous and normal cells.\u003c/p\u003e\n\u003cp\u003eIncreasing the frequency can cause variations in the membrane potential of cells due to electromagnetic fields. As such, the electrical characteristics of cancer cells may be altered by high-frequency electrical currents. This change frequently appears as a decrease in the resistance and capacitance values inside the cells, which eventually results in a decrease in the magnitude of the cell impedance. This effect is demonstrated in Figure 8, which shows the reduced impedance values found in both malignant and non-cancerous cells.\u003c/p\u003e\n\u003cp\u003eIn order to facilitate frequency-dependent single-cell impedance analysis, this study presents a simple microchamber array for impedance measurement. A PDMS cover maintains uniform cell-to-electrode connections within each microchamber. By adjusting cell concentrations and measuring cell-to-electrode contact rates, we used simulation to verify single-cell entrapment and contact stability. IEC-6 cells showed greater impedance magnitudes (60.07\u0026ndash;154.36k\u0026Omega;) in the 95.6 kHz\u0026ndash;2 MHz frequency range when compared to SW-480 human colon cancer cells in the impedance analysis. Furthermore, in the frequency range of 4.37 kHz to 2 MHz, IEC-6 cells showed greater impedance phases (3.96\u0026ndash;20.80\u0026deg;) than human colon cancer cells. As a result, compared to CCD-18 cell lines (271k\u0026Omega; and 7.01nF), cancer cells showed reduced resistance and capacitance (241k\u0026Omega; and 3.13nF), showing clear distinctions between healthy and malignant colon cells. Our microchamber array demonstrated consistent cell-to-electrode contact and effective single-cell loading, which made it easier to distinguish between cancerous and healthy cells. This process provides a viable method for describing the characteristics of cancer cells.\u003c/p\u003e"},{"header":"V.\tCONCLUSION","content":"\u003cp\u003eIn order to facilitate the evaluation of single-cell electrical properties, this work offers a microchamber array that is intended for simple measurement of capacitance and resistance. Each microchamber is equipped with a PDMS cover that guarantees robust cell-to-electrode connections. The method for determining each cell\u0026apos;s unique organic electrical characteristics is described in this paper. Because of the high sensitivity of our model, we can precisely identify changes in the electrical characteristics of cells. Our study combines microfluidics\u0026apos; high-throughput capabilities with sensitive microelectromechanical systems (MEMS) technology measurements to carry out biophysical characterization of circulating cells for diagnostic purposes. SW480 human colon cancer cells showed lower resistance levels in the electrical investigation than did IEC-6 cells. As thus, compared to normal colon cells (271k\u0026Omega; and 7.01nF), cancer cells showed reduced resistance and capacitance values (241k\u0026Omega; and 3.13nF). At a frequency of 50 KHz significant difference is observed between normal cells (700k\u0026Omega;) and cancer cells (608k\u0026Omega;) in magnitude response. We demonstrated by simulation that the microchamber array may be used to discriminate between normal and cancerous cells by facilitating straightforward single-cell loading and preserving stable cell-to-electrode connections.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eThis work is not funded by any organization. Facilities were provided by MEMS Lab, KL University\u003c/p\u003e\n\u003cp\u003eAcknowledgment\u003c/p\u003e\n\u003cp\u003eWe acknowledge that a portion of our research was conducted using the facilities at the MEMS Lab, KLEF.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMohajerzadeh, Single-cell resolution diagnosis of cancer cells by carbon nanotube electrical spectroscopy, Nanoscale, The Royal Society of Chemistry 2013, DOI: 10.1039/c3nr33430a\u003c/li\u003e\n\u003cli\u003eGrossi and B. Ricc\u0026ograve;: E.I.S. for biological analysis and food characterization, J. Sens. Sens. 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(2019), \u0026lsquo;Design and F.E.M. model analysis of MEMS cantilever structure for detection of colon cancer using mass sensing\u0026rsquo;, Research Journal of Pharmacy and Technology, 12(9), PP.4250-4254.\u003c/li\u003e\n\u003cli\u003eZhang, Z.; Huang, X.; Liu,K.; Lan, T.;Wang, Z.; Zhu, Z. Recent Advances in Electrical Impedance Sensing Technology for Single-Cell Analysis. Biosensors 2021, 11, 470.\u003c/li\u003e\n\u003cli\u003eBarbosa, A. I.,\u0026nbsp;Borges, J.,\u0026nbsp;Meira, D. I.,\u0026nbsp;Costa, D.,\u0026nbsp;Rodrigues, M. S.,\u0026nbsp;Rebelo, R.,\u0026nbsp;Correlo, V. M.,\u0026nbsp;Vaz, F., \u0026amp;\u0026nbsp;Reis, R. L.\u0026nbsp;(2019).\u0026nbsp;Development of label-free plasmonic Au-TiO2 thin film immunosensor devices.\u0026nbsp;Materials Science and Engineering C,\u0026nbsp;100,\u0026nbsp;424\u0026ndash;432.\u003c/li\u003e\n\u003cli\u003eVineetha K.V., Kumar P.A., Sailaja B.V.S., Guha K., Sravani K.G., Rao K.S. ( 2018) , \u0026lsquo;Design of MEMS sensor for the detection of cholera and diarrehea by capacitance modulation\u0026rsquo;,Microsystem Technologies, 24 (8), P.P. 3371- 3379\u003c/li\u003e\n\u003cli\u003eRao K.S., Vineetha K.V., Sailaja B.V.S., Guha K., Maity N.P., Maity R., Sravani K.G. ( 2018) , \u0026lsquo;Design, simulation and performance analysis bio-sensors for the detection of cholera and diarrhea using MEMS technology\u0026rsquo;,Microsystem Technologies, (), P.P. 1- 23\u003c/li\u003e\n\u003cli\u003eSiddaiah N., Prasad G.R.K., Sai Pravallika S.S., Sai Prasanna G.V.S., Raja Gopal R.R. ( 2018) , \u0026lsquo;Performance of analysis crab leg based RF MEMS switch for defense and aerospace applications\u0026rsquo;,International Journal of Engineering and Technology(U.A.E.), 7 (1.5), P.P. 71- 76\u003c/li\u003e\n\u003cli\u003eJayavardhani K., Noureen Fathima S.K., Bhima Sankar K., Kavya Sri K., Sunithamani S. ( 2018) , \u0026lsquo;Design and simulation of low actuation voltage RF MEMS shunt capacitive switch with serpentine flexures \u0026amp; rectangular perforations\u0026rsquo;, International Journal of Engineering and Technology(U.A.E.), 7 (2), P.P. 4- 8\u003c/li\u003e\n\u003cli\u003eRao K.S., Jasti S. (2017),\u0026rsquo;Design and analysis of MEMS based bio sensor for T.B. detection\u0026rsquo;,2016 International Conference on Electrical, Electronics, Communication, Computer and Optimization Techniques, ICEECCOT 2016,PP.361-365.\u003c/li\u003e\n\u003cli\u003eYarraguntla N., Tirumala N., Shameem S., Rao K.S. ( 2018) , \u0026lsquo;Detection of Hepatitis viruses (HBV, H.A.V., HCV) in serum using MEMS based Bio-Sensor\u0026rsquo;,Proceedings of the 2nd International Conference on Computing Methodologies and Communication, ICCMC 2018, , P.P. 405- 409.\u003c/li\u003e\n\u003cli\u003eSubra Suresh, Biomechanics and biophysics of cancer cells, Acta Biomater. 2007, 3(4): 413\u0026ndash;438.\u003c/li\u003e\n\u003cli\u003eRamdane A. Harouaka, Circulating tumor cell enrichment based on physical properties, J Lab Autom. 2013 December; 18(6).\u003c/li\u003e\n\u003cli\u003eVasudha C. Shukla, Lab-on-a-Chip Platforms for Biophysical Studies of Cancer with Single-Cell Resolution, Trends in biotechnology,2018,1-13.\u003c/li\u003e\n\u003cli\u003eSharda Yadav, Biophysical properties of cells for cancer diagnosis, Journal of Biomechanics 86 (2019) 1\u0026ndash;7\u003c/li\u003e\n\u003cli\u003eNa Liu, Microfluidic-Based Mechanical Phenotyping of Androgen-Sensitive and Non-sensitive Prostate Cancer Cells Lines, Micromachines 2019, 10, 602.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTABLE I.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eelectrode chamber :Measurements\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.54961832061068%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eElements\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.229007633587788%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eSymbol\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.221374045801525%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eDimensions[\u0026mu;m]\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.54961832061068%\" valign=\"top\"\u003e\n \u003cp\u003eChamber width\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.229007633587788%\" valign=\"top\"\u003e\n \u003cp\u003eL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.221374045801525%\" valign=\"top\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.54961832061068%\" valign=\"top\"\u003e\n \u003cp\u003eChamber height\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.229007633587788%\" valign=\"top\"\u003e\n \u003cp\u003eHc\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.221374045801525%\" valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.54961832061068%\" valign=\"top\"\u003e\n \u003cp\u003eElectrode gap\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.229007633587788%\" valign=\"top\"\u003e\n \u003cp\u003eG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.221374045801525%\" valign=\"top\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.54961832061068%\" rowspan=\"2\"\u003e\n \u003cp\u003eElectrode width\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.229007633587788%\" valign=\"top\"\u003e\n \u003cp\u003eW1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.221374045801525%\" valign=\"top\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.91925465838509%\" valign=\"top\"\u003e\n \u003cp\u003eW2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"67.0807453416149%\" valign=\"top\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.54961832061068%\" valign=\"top\"\u003e\n \u003cp\u003eElectrode height\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.229007633587788%\" valign=\"top\"\u003e\n \u003cp\u003eHe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.221374045801525%\" valign=\"top\"\u003e\n \u003cp\u003e2000(A)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eTable 2 Impedance magnitude values of normal colon cell \u0026amp; cancer cell\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"295\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.23728813559322%\"\u003e\n \u003cp\u003e\u003cstrong\u003eFrequency(Hz)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.88135593220339%\"\u003e\n \u003cp\u003e\u003cstrong\u003eNon-cancer Impedance magnitude(Ω)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.88135593220339%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCancer Impedance magnitude(Ω)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.23728813559322%\"\u003e\n \u003cp\u003e200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.88135593220339%\"\u003e\n \u003cp\u003e7682215\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.88135593220339%\"\u003e\n \u003cp\u003e7110450\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.23728813559322%\"\u003e\n \u003cp\u003e10000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.88135593220339%\"\u003e\n \u003cp\u003e2360265\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.88135593220339%\"\u003e\n \u003cp\u003e1984051\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.23728813559322%\"\u003e\n \u003cp\u003e50000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.88135593220339%\"\u003e\n \u003cp\u003e700000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.88135593220339%\"\u003e\n \u003cp\u003e608000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.23728813559322%\"\u003e\n \u003cp\u003e250000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.88135593220339%\"\u003e\n \u003cp\u003e205000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.88135593220339%\"\u003e\n \u003cp\u003e132000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.23728813559322%\"\u003e\n \u003cp\u003e466820\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.88135593220339%\"\u003e\n \u003cp\u003e155000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.88135593220339%\"\u003e\n \u003cp\u003e87200\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.23728813559322%\"\u003e\n \u003cp\u003e666800\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.88135593220339%\"\u003e\n \u003cp\u003e95000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.88135593220339%\"\u003e\n \u003cp\u003e83000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.23728813559322%\"\u003e\n \u003cp\u003e800120\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.88135593220339%\"\u003e\n \u003cp\u003e88510\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.88135593220339%\"\u003e\n \u003cp\u003e71600\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.23728813559322%\"\u003e\n \u003cp\u003e1066760\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.88135593220339%\"\u003e\n \u003cp\u003e75800\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.88135593220339%\"\u003e\n \u003cp\u003e64800\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.23728813559322%\"\u003e\n \u003cp\u003e1200080\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.88135593220339%\"\u003e\n \u003cp\u003e70000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.88135593220339%\"\u003e\n \u003cp\u003e58360\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.23728813559322%\"\u003e\n \u003cp\u003e1400060\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.88135593220339%\"\u003e\n \u003cp\u003e66300\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.88135593220339%\"\u003e\n \u003cp\u003e57200\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.23728813559322%\"\u003e\n \u003cp\u003e1666700\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.88135593220339%\"\u003e\n \u003cp\u003e62000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.88135593220339%\"\u003e\n \u003cp\u003e54900\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"MEMS, Resistance, capacitance, Colorectal Cancer, conductivity, permittivity","lastPublishedDoi":"10.21203/rs.3.rs-4217196/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4217196/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Investigating the bioelectrical characteristics of individual cells can provide important information about many aspects of cellular processes and their roles in general health and disease conditions. Comprehending these attributes at the cellular level facilitates a more intricate comprehension of physiological mechanisms and creates novel opportunities for disease detection, management, and even averting. It's fascinating to observe how new methods and technological developments are allowing us to learn more about the intricacies of cellular biology and how they relate to human health. Since cancer cells have slightly lower capacitance and resistance values, the bioelectrical properties could be used as biomarkers for early cancer identification. Measurements were conducted on the capacitance and resistance of individual normal cell lines (IEC-6), and highly-invasive malignant (SW480) colon cancer cells using MEMS sensors during simulations. Normal cell resistance is 318kΩ, while normal cell capacitance is 8.12nF. These values differ from those of cancer cells, which have variable resistance and capacitance values (246kΩ and 3.91nF for SW480). At a frequency range of 200 Hz to 2 MHz significant difference is observed in impedance magnitude response values between normal cells (7.7 MΩ to 62kΩ) and cancer cells (7.1 MΩ to 54.9kΩ).","manuscriptTitle":"Development of a MEMS-Based Biosensor for Analyzing the Bio-Electrical Characteristics of Colon Cancer Cells","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-19 18:22:50","doi":"10.21203/rs.3.rs-4217196/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"bce4153e-76a6-4e28-8bb8-cf2c4e498bc8","owner":[],"postedDate":"April 19th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-05-24T12:39:21+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-19 18:22:50","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4217196","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4217196","identity":"rs-4217196","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

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