Engineering a 3D human intracranial aneurysm model using liquid-assisted injection molding and tuned hydrogels.

Physiologically relevant intracranial aneurysm (IA) models are crucially required to facilitate testing treatment options for IA. Herein, we report the development of a new in vitro tissue-engineered platform, which recapitulates the microenvironment, structure, and cellular complexity of native human IA. A new modified liquid-assisted injection molding technique was developed to fabricate a three-dimensional hollow IA model with clinically relevant IA dimensions within a mechanically tuned Gelatin Methacryloyl (GelMA) hydrogel. An endothelium lining was created inside the IA model by culturing human umbilical vein endothelial cells over pre-cultured human brain vascular smooth muscle cells. These cellularized IA models were subjected to medium perfusion at flow rates between 6.3 and 15.75 mL/min for inducing biomimetic vessel wall shear stress (10-25 dyn/cm2) to the cells for ten days. Both cell types maintained their secretome profiles and showed more than 96% viability, demonstrating the biocompatibility of the hydrogel during perfusion cell culture at such flow rates. Based on the characterized viscoelastic properties of the GelMA hydrogel and with the aid of a fluid-structure interaction model, the capability of the IA model in predicting the response of the IA to different fluid flow profiles was mathematically shown. With physiologically relevant behavior, our developed in vitro human IA model could allow researchers to better understand the pathophysiology and treatment of IA. STATEMENT OF SIGNIFICANCE: A three-dimensional intracranial aneurysm (IA) tissue model recapitulating the microenvironment, structure, and cellular complexity of native human IA was developed. • An endothelium lining was created inside the IA model over pre-cultured human brain vascular smooth muscle cells over at least 10-day successful culture. • The cells maintained their secretome profiles, demonstrating the biocompatibility of hydrogel during a long-term perfusion cell culture. • The IA model showed its capability in predicting the response of IA to different fluid flow profiles. • The cells in the vessel region behaved differently from cells in the aneurysm region due to alteration in hemodynamic shear stress. • The IA model could allow researchers to better understand the pathophysiology and treatment options of IA.

A tuned gelatin methacryloyl (GelMA) hydrogel facilitates myelination of dorsal root ganglia neurons in vitro.

Investigating axonal myelination by Schwann cells (SCs) is crucial for understanding mechanisms underlying demyelination and remyelination, which may help gain insights into incurable disorders like neurodegenerative diseases. In this study, a gelatin-based hydrogel, gelatin methacryloyl (GelMA), was optimized to achieve the biocompatibility, porosity, mechanical stability, and degradability needed to provide high cell viability for dorsal root ganglia (DRG) neurons and SCs, and to enable their long-term coculture needed for myelination studies. The results of cell viability, neurite elongation, SC function and maturation, SC-axon interaction, and myelination were compared with two other commonly used substrates, namely collagen and Poly-d Lysine (PDL). The tuned GelMA constructs (Young's modulus of 32.6 ± 1.9 kPa and the median value of pore size of 10.3 µm) enhanced single axon generation (unlike collagen) and promoted the interaction of DRG neurons and SCs (unlike PDL). While DRG cells exhibited relatively higher viability on PDL after 48 h, i.e., 83.8%, the cells had similar survival rate on GelMA and collagen substrates, 66.7% and 61.5%, respectively. Further adjusting the hydrogel properties to achieve two distinct ranges of relatively small and large pores supported SCs to extend their processes freely and enabled physical contact with and wrapping around their corresponding axons. Staining the cells with myelin basic protein (MBA) and myelin-associated glycoprotein (MAG) revealed enhanced myelination on GelMA hydrogel compared to PDL and collagen. Moreover, the engineered porosity enhanced DRGs and SCs attachments and flexibility of movement across the substrate. This engineered hydrogel structure can now be further explored to model demyelination in neurodegenerative diseases, as well as to study the effects of various compounds on myelin regeneration.

Role of temperature on bio-printability of gelatin methacryloyl bioink in two-step cross-linking strategy for tissue engineering applications.

Additive manufacturing has shown promising results in reconstructing three-dimensional (3D) living tissues for various applications, including tissue engineering, regenerative medicine, drug discovery, and high-throughput drug screening. In extrusion-based bioprinters, stable formation of filaments and high-fidelity deposition of bioinks are the primary challenges in fabrication of physiologically relevant tissue constructs. Among various bioinks, gelatin methacryloyl (GelMA) is known as a photocurable and physicochemically tunable hydrogel with a demonstrated biocompatibility and tunable biodegradation properties. The two-step crosslinking of GelMA (reversible thermal gelation and permanent photo-crosslinking) has attracted researchers to make complex tissue constructs. Despite promising results in filament formation and printability of this hydrogel, the effect of temperature on physicochemical properties, cytocompatibility, and biodegradation of the hydrogel are to be investigated. This work studies the effect of thermoreversible, physical crosslinking on printability of GelMA. The results of 3D printing of GelMA at different temperatures followed by irreversible chemical photo-crosslinking show that the decrease in temperature improves the filament formation and shape fidelity of the deposited hydrogel, particularly at the temperatures around 15 °C. Time dependant mechanical testing of the printed samples revealed that decreasing the extruding temperature increases the elastic properties of the extruded filaments. Furthermore, our novel approach in minimizing the slippage effect during rheological study enabled to measure changes in linear and non-linear viscoelastic properties of the printed samples at different temperatures. A considerable increase in storage modulus of the extruded samples printed at lower temperatures confirms their higher solid behavior. Scanning electron microscopy revealed a remarkable decrease in porosity of the extruded hydrogels by decreasing the temperature. Chemical analysis by Fourier-transform infrared spectroscopy and circular dichroism showed a direct relationship between the coil-helix transition in hydrogel macromers and its physical alterations. Finally, biodegradation and cytocompatibility of the extruded hydrogels decreased at lower extruding temperatures.

Effect of cell imprinting on viability and drug susceptibility of breast cancer cells to doxorubicin.

This study demonstrates the effect of substrate's geometrical cues on viability and the efficacy of an anti-cancer drug, doxorubicin (DOX), on breast cancer cells. It is hypothesized that the surface topographical properties can mediate the cellular drug intake. Pseudo-three dimensional (3D) platforms were fabricated using imprinting technique from polydimethylsiloxane (PDMS) and gelatin methacryloyl (GelMA) hydrogel to recapitulate topography of cells' membranes. The cells exhibited higher viability on the cell-imprinted platforms for both PDMS and GelMA materials compared to the plain/flat counterparts. For instance, MCF7 cells showed a higher metabolic activity (11.9%) on MCF7-imprinted PDMS substrate than plain PDMS. The increased metabolic activity for the imprinted GelMA was about 44.2% compared to plain hydrogel. The DOX response of cells was monitored for 24 h. Although imprinted substrates demonstrated enhanced biocompatibility, the cultured cells were more susceptible to the drug compared to the plain substrates. In particular, MCF7 cells on imprinted PDMS and GelMA substrates showed 37% and 50% higher in cell death compared to the corresponding plain PDMS and GelMA, respectively. Interestingly, the drug susceptibility of the cells on the imprinted hydrogel was about 70% higher than the cells cultured on imprinted PDMS substrates. Having MCF7 cell-imprinted substrates, DOX responses of two other breast cancer cell lines, SKBR3 and ZR-75-1, were also evaluated. The results support that cell membrane curvature developed by multiscale topography is able to mediate intracellular signaling and drug intake. STATEMENT OF SIGNIFICANCE: Research in biological sciences and drug discovery mostly rely on two dimensional (2D) cell culture techniques which cannot provide a reliable physiologically relevant environment. Lack of extracellular matrix and a large shift in physicochemical properties of conventional 2D substrates can induce aberrant cellular behaviors. While chemical composition, topographical, and mechanical properties of substrates have remarkable impacts on drug susceptibility, gene expression, and protein synthesis, the most cell culture plates are from rigid and plain substrates. A number of (bio)polymeric 3D-platforms have been introduced to resemble innate cell microenvironment. However, their intricate culture protocols restrain their applications in demanding high-throughput drug screening. To address the above concerns, in the present study, a hydrogel-based pseudo-3D substrate with imprinted cell features has been introduced.

Scalable microfabrication of drug-loaded core-shell tablets from a single erodible polymer with adjustable release profiles.

Oral tablets with tunable release profiles have emerged to enhance the effectiveness of therapies in different clinical conditions. Although the concept of tablets with adjustable release profiles has been studied before, the lack of a fast and scalable production technique has limited their widespread application. In this study, a scalable fabrication method was developed to manufacture controlled-release polyanhydride tablets. A new polymeric core-shell tablet design is also proposed, that in conjunction with a micro-fabrication procedure, allows for achieving tunable release profiles required in personalized medicine in small-size tablets. Utilizing a surface-erodible polymeric carrier in the fabrication of the new tablet design resulted in achieving adjustable release profiles and improvements in the drug-loading capacity of the delivery system which allows for delivering a flexible amount of therapeutics with desirable patterns to patients. The proposed fabrication techniques allow for scalable production of personalized tablets with the high resolution required in precision medicine and hence have a high potential for clinical translation.

Picoliter agar droplet breakup in microfluidics meets microbiology application: numerical and experimental approaches.

Droplet microfluidics has provided lab-on-a-chip platforms with the capability of bacteria encapsulation in biomaterials, controlled culture environments, and live monitoring of growth and proliferation. The droplets are mainly generated from biomaterials with temperature dependent gelation behavior which necessitates stable and size-controlled droplet formation within microfluidics. Here, the biomaterial is agar hydrogel with a non-Newtonian response at operating temperatures below 40 °C, the upper-temperature threshold for cells and pathogens. The size of the produced droplets and the formation regimes are examined when the agar is injected at a constant temperature of 37 °C with agar concentrations of 0.5%, 1%, and 2% and different flow rate ratios of the dispersed phase to the continuous phase (φ: 0.1 to 1). The numerical simulations show that φ and the capillary number (Ca) are the key parameters controlling the agar droplet size and formation regime, from dripping to jetting. Also, increasing the agar concentration produces smaller droplets. The simulation data were validated against experimental agar droplet generation and transport in microfluidics. This work helps to understand the physics of droplet generation in droplet microfluidic systems operating with non-Newtonian fluids. Pathogenic bacteria were successfully cultured and monitored in high resolution in agar droplets for further research in antibiotic susceptibility testing in bacteremia and urinary tract infection.

Sandwich-structured nanoparticles-grafted functionalized graphene based 3D nanocomposites for high-performance biosensors to detect ascorbic acid biomolecule.

We present a highly sensitive and selective nano-biosensor for rapid, stable and highly reproducible detection of ascorbic acid (AA) in the presence of dopamine, uric acid and other interferences by a three-layer sandwich arrangement of nitrogen-doped functionalized graphene (NFG), silver nanoparticles (AgNPs) and nanostructured polyaniline (PANI) nanocomposite. The enhanced AA electrochemical properties of the NFG/AgNPs/PANI electrode is attributed to the superior conductivity of the NFG-PANI and the excellent catalytic activity of AgNPs. The critical modification of the AgNPs-grafted NFG-PANI coated on very low-cost fluorine doped tin oxide electrode (FTOE) increased the charge transfer conductivity of the electrode (the resistance drops down from 11,000 Ω to 6 Ω). The nano-biosensor was used to accurately detect AA in vitamin C tablets with the recovery of 98%. The sensor demonstrated a low detection limit of 8 µM (S/N = 3) with a very wide linear detection range of 10-11,460 µM, good reproducibility and excellent selectivity performance for AA detection. The results demonstrate that this nanocomposite is a promising candidate for rapid and selective detection of AA in practical clinical samples.

In vitro models and systems for evaluating the dynamics of drug delivery to the healthy and diseased brain.

The blood-brain barrier (BBB) plays a crucial role in maintaining brain homeostasis and transport of drugs to the brain. The conventional animal and Transwell BBB models along with emerging microfluidic-based BBB-on-chip systems have provided fundamental functionalities of the BBB and facilitated the testing of drug delivery to the brain tissue. However, developing biomimetic and predictive BBB models capable of reasonably mimicking essential characteristics of the BBB functions is still a challenge. In addition, detailed analysis of the dynamics of drug delivery to the healthy or diseased brain requires not only biomimetic BBB tissue models but also new systems capable of monitoring the BBB microenvironment and dynamics of barrier function and delivery mechanisms. This review provides a comprehensive overview of recent advances in microengineering of BBB models with different functional complexity and mimicking capability of healthy and diseased states. It also discusses new technologies that can make the next generation of biomimetic human BBBs containing integrated biosensors for real-time monitoring the tissue microenvironment and barrier function and correlating it with the dynamics of drug delivery. Such integrated system addresses important brain drug delivery questions related to the treatment of brain diseases. We further discuss how the combination of in vitro BBB systems, computational models and nanotechnology supports for characterization of the dynamics of drug delivery to the brain.

Cyclic Stretch Effects on Adipose-Derived Stem Cell Stiffness, Morphology and Smooth Muscle Cell Gene Expression.

Recent investigations consider adipose-derived stem cells (ASCs) as a promising source of stem cells for clinical therapies. To obtain functional cells with enhanced cytoskeleton and aligned structure, mechanical stimuli are utilized during differentiation of stem cells to the target cells. Since function of muscle cells is associated with cytoskeleton, enhanced structure is especially essential for these cells when employed in tissue engineering. In this study by utilizing a custom-made device, effects of uniaxial tension (1Hz, 10% stretch) on cytoskeleton, cell alignment, cell elastic properties, and expression of smooth muscle cell (SMC) genes in ASCs are investigated. Due to proper availability of ASCs, results can be employed in cardiovascular engineering when production of functional SMCs in arterial reconstruction is required. Results demonstrated that cells were oriented after 24 hours of cyclic stretch with aligned pseudo-podia. Staining of actin filaments confirmed enhanced polymerization and alignment of stress fibers. Such phenomenon resulted in stiffening of cell body which was quantified by atomic force microscopy (AFM). Expression of SM α-actin and SM22 α-actin as SMC associated genes were increased after cyclic stretch while GAPDH was considered as internal control gene. Finally, it was concluded that application of cyclic stretch on ASCs assists differentiation to SMC and enhances functionality of cells.

An electrical bio-chip to transfer and detect electromagnetic stimulation on the cells based on vertically aligned carbon nanotubes.

A highly sensitive impedimetric bio-chip based on vertically aligned multiwall carbon nanotubes (VAMWCNTs), was applied in direct interaction with lung cancer cells. Our tool provided both inducing and monitoring the bioelectrical changes in the cells initiated by electromagnetic (EM) wave stimulation. EM wave of 940MHz frequency with different intensities was used. Here, wave ablation might accumulate electrical charge on the tips of nanotubes penetrated into cell's membrane. The charge might induce ionic exchanges into the cell and cause alterations in electrical states of the membrane. Transmembrane electrostatic/dynamic states would be strongly affected due to such exchanges. Our novel modality was that, the cells' vitality changes caused by charge inductions were electrically detected with the same nanotubes in the architecture of electrodes for impedance measurement. The responses of the sensor were confirmed by electron and florescent microscopy images as well as biological assays. In summation, our method provided an effective biochip for enhancing and detecting external EM stimulation on the cells useful for future diagnostic and therapeutic applications, such as wave-guided drug-resistance breakage.

Dual effect of F-actin targeted carrier combined with antimitotic drug on aggressive colorectal cancer cytoskeleton: Allying dissimilar cell cytoskeleton disrupting mechanisms.

A recent approach to colon cancer therapy is to employ selective drugs with specific extra/intracellular sites of action. Alteration of cytoskeletal protein reorganization and, subsequently, to cellular biomechanical behaviour during cancer progression highly affects the cancer cell progress. Hence, cytoskeleton targeted drugs are an important class of cancer therapy agents. We have studied viscoelastic alteration of the human colon adenocarcinoma cell line, SW48, after treatment with a drug delivery system comprising chitosan as the carrier and albendazole as the microtubule-targeting agent (MTA). For the first time, we have evaluated the biomechanical characteristics of the cell line, using the micropipette aspiration (MA) method after treatment with drug delivery systems. Surprisingly, employing a chitosan-albendazole pair, in comparison with both neat materials, resulted in more significant change in the viscoelastic parameters of cells, including the elastic constants (K1 and K2) and the coefficient of viscosity (µ). This difference was more pronounced for cancer cells after 48h of the treatment. Microtubule and actin microfilament (F-actin) contents in the cell line were studied by immunofluorescent staining. Good agreement was observed between the mechanical characteristics results and microtubule/F-actin contents of the treated SW48 cell line, which declined after treatment. The results showed that chitosan affected F-actin more, while MTA was more effective for microtubules. Toxicity studies were performed against two cancer cell lines (SW48 and MCF10CA1h) and compared to normal cells, MCF10A. The results showed cancer selectiveness, safety of formulation, and enhanced anticancer efficacy of the CS/ABZ conjugate. This study suggests that employing such a suitable pair of drug-carriers with dissimilar sites of action, thus allying the different cell cytoskeleton disrupting mechanisms, may provide a more efficient cancer therapy approach.

Skin Diseases Modeling using Combined Tissue Engineering and Microfluidic Technologies.

In recent years, both tissue engineering and microfluidics have significantly contributed in engineering of in vitro skin substitutes to test the penetration of chemicals or to replace damaged skins. Organ-on-chip platforms have been recently inspired by the integration of microfluidics and biomaterials in order to develop physiologically relevant disease models. However, the application of organ-on-chip on the development of skin disease models is still limited and needs to be further developed. The impact of tissue engineering, biomaterials and microfluidic platforms on the development of skin grafts and biomimetic in vitro skin models is reviewed. The integration of tissue engineering and microfluidics for the development of biomimetic skin-on-chip platforms is further discussed, not only to improve the performance of present skin models, but also for the development of novel skin disease platforms for drug screening processes.

Microfluidic integrated acoustic waving for manipulation of cells and molecules.

Acoustophoresis with its simple and low-cost fabrication, rapid and localized fluid actuation, compatibility with microfluidic components, and biocompatibility for cellular studies, has been extensively integrated into microfluidics to provide on-chip microdevices for a variety of applications in biology, bioengineering and chemistry. Among different applications, noninvasive manipulation of cells and biomolecules are significantly important, which are addressed by acoustic-based microfluidics. Here in this paper, we briefly explain the principles and different configurations of acoustic wave and acoustic streaming for the manipulation of cells and molecules and overview its applications for single cell isolation, cell focusing and sorting, cell washing and patterning, cell-cell fusion and communication, and tissue engineering. We further discuss the application of acoustic-based microfluidic systems for the mixing and transport of liquids, manipulation of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) molecules, followed by explanation on the present challenges of acoustic-based microfluidics for the handling of cells and molecules, and highlighting the future directions.

Microfluidic Manipulation of Core/Shell Nanoparticles for Oral Delivery of Chemotherapeutics: A New Treatment Approach for Colorectal Cancer.

A microfluidics approach to synthesize core-shell nanocarriers with high pH tunability is described. The sacrificial shell protects the core layer with the drugs and prevents their release in the severe pH conditions of the gastrointestinal tract, while allowing for drug release in the proximity of a tumor. The proposed nanoparticulate drug-delivery system is designed for the oral administration of cancer therapeutics.

Effects of uniaxial cyclic stretch loading on morphology of adipose derived stem cells.

Adipose derived stem cells (ADSC) are good candidates for the replacement of bone marrow derived mesenchymal stem cells due to their abundance, multipotency property, and easier accessibility. In order to explore the behavior of these cells in response to mechanical stimulation, in this study we have investigated the effects of uniaxial dynamic mechanical loading on ADSC's morphology. Stem cells derived from the fat tissue of human and after an overnight culture were seeded on a silicone rubber strips. Afterwards, cells were subjected to a uniaxial dynamic loading in three different groups. Cell images were evaluated considering different morphological parameters. Fractal dimension decreased significantly after loading while in control groups there were a significant increase (p<0.05), approving that cyclic strain would lead to more aligned and organized cells. Cell orientation also increased significantly (p<0.05). Moreover cells' orientation angle, 24 hour after loading does not change compared to the observations immediately after loading, which attests to the practicality of the cyclic strain in functional tissue engineering. Cell width decreased and cell length increased which led to a significant increase in cell shape index (p<0.05). Results confirmed that uniaxial dynamic loading affects cell morphological parameters comparing their values before and after loading. In addition, the number of cycles are also an important factor since different number of cycles lead to different amounts of certain morphological parameters. Conclusively, cyclic strain can be a practical method in the field of functional tissue engineering.

Effects of hypergravity on adipose-derived stem cell morphology, mechanical property and proliferation.

Alteration in specific inertial conditions can lead to changes in morphology, proliferation, mechanical properties and cytoskeleton of cells. In this report, the effects of hypergravity on morphology of Adipose-Derived Stem Cells (ADSCs) are indicated. ADSCs were repeatedly exposed to discontinuous hypergravity conditions of 10 g, 20 g, 40 g and 60 g by utilizing centrifuge (three times of 20 min exposure, with an interval of 40 min at 1 g). Cell morphology in terms of length, width and cell elongation index and cytoskeleton of actin filaments and microtubules were analyzed by image processing. Consistent changes observed in cell elongation index as morphological change. Moreover, cell proliferation was assessed and mechanical properties of cells in case of elastic modulus of cells were evaluated by Atomic Force Microscopy. Increase in proliferation and decrease in elastic modulus of cells are further results of this study. Staining ADSC was done to show changes in cytoskeleton of the cells associated to hypergravity condition specifically in microfilament and microtubule components. After exposing to hypergravity, significant changes were observed in microfilaments and microtubule density as components of cytoskeleton. It was concluded that there could be a relationship between changes in morphology and MFs as the main component of the cells.

Monitoring the spreading stage of lung cells by silicon nanowire electrical cell impedance sensor for cancer detection purposes.

We developed a silicon nanowire based electrical cell impedance sensor (SiNW-ECIS) as an instrument that detects cancerous cultured living lung cells by monitoring their spreading state at which the cells stretched and become extended on nanowires. Further current penetration into the extended membrane of malignant cells in respect to normal ones (In the first 6h after cells interaction with surface) are the key mechanism in our diagnosis procedure. The developed device applied to monitor the spreading-induced electrical differences between cancerous and normal lung cells in an integral fashion. Detection was performed so faster than the time required to complete cells mitosis. Morphology and architecture of doped Si nanowires covered microelectrodes observably enhance the contact area between cells and electrodes which support accurate signal recording from stretched cells as indicated by SEM and florescent images.

Prediction of neural differentiation fate of rat mesenchymal stem cells by quantitative morphological analyses using image processing techniques.

Differentiation of bone marrow mesenchymal stem cells (BMSCs) into neural cells has received significant attention in recent years. However, there is still no practical method to evaluate differentiation process non-invasively and practically. The cellular quality evaluation method is still limited to conventional techniques, which are based on extracting genes or proteins from the cells. These techniques are invasive, costly, time consuming, and should be performed by relevant experts in equipped laboratories. Moreover, they cannot anticipate the future status of cells. Recently, cell morphology has been introduced as a feasible way of monitoring cell behavior because of its relationship with cell proliferation, functions and differentiation. In this study, rat BMSCs were induced to differentiate into neurons. Subsequently, phase contrast images of cells taken at certain intervals were subjected to a series of image processing steps and cell morphology features were calculated. In order to validate the viability of applying image-based approaches for estimating the quality of differentiation process, neural-specific markers were measured experimentally throughout the induction. The strong correlation between quantitative imaging metrics and experimental outcomes revealed the capability of the proposed approach as an auxiliary method of assessing cell behavior during differentiation.

A single-cell correlative nanoelectromechanosensing approach to detect cancerous transformation: monitoring the function of F-actin microfilaments in the modulation of the ion channel activity.

Cancerous transformation may be dependent on correlation between electrical disruptions in the cell membrane and mechanical disruptions of cytoskeleton structures. Silicon nanotube (SiNT)-based electrical probes, as ultra-accurate signal recorders with subcellular resolution, may create many opportunities for fundamental biological research and biomedical applications. Here, we used this technology to electrically monitor cellular mechanosensing. The SiNT probe was combined with an electrically activated glass micropipette aspiration system to achieve a new cancer diagnostic technique that is based on real-time correlation between mechanical and electrical behaviour of single cells. Our studies demonstrated marked changes in the electrical response following increases in the mechanical aspiration force in healthy cells. In contrast, such responses were extremely weak for malignant cells. Confocal microscopy results showed the impact of actin microfilament remodelling on the reduction of the electrical response for aspirated cancer cells due to the significant role of actin in modulating the ion channel activity in the cell membrane.

Silicon nanograss based impedance biosensor for label free detection of rare metastatic cells among primary cancerous colon cells, suitable for more accurate cancer staging.

Detection of rare metastatic cells within a benign tumor is a key challenge to diagnose the cancerous stage of the patients tested by clinical human biopsy or pap smear samples. We have fabricated and tested a nanograssed silicon based bioelectronic device with the ability of detecting a few human colon invasive cancer cells (SW48) in a mixed cell culture of primary cancerous colon cells (HT29) without any biochemical labels. A discernible impedance change was elicited after the presence of 5% metastatic cells in the whole benign sample. The electric field penetration as well as current flow to metastatic cells is different from benign ones due to their different membrane dielectric parameters. Beta dispersion as one of intrinsic bioelectrical properties of the cell membrane in blocking the stimulating current flow in the range of kHz is the specific parameter involved in our diagnosis approach. It can reflect in-depth information about the dielectric properties and the pathological condition of a cell before and after metastatic transformation. Electrically active doped silicon nanograss structures owing to their superior nanocontacts with cell membrane can detect any slight variations in current being originated from the presence of rare metastatic cells on the surface of the sensing electrode. The experimental results revealed that bare doped silicon microelectrodes are incapable of resolving different grades of attached cells.