Step-by-step fabrication of heart-on-chip systems as models for cardiac disease modeling and drug screening.

Cardiovascular diseases are caused by hereditary factors, environmental conditions, and medication-related issues. On the other hand, the cardiotoxicity of drugs should be thoroughly examined before entering the market. In this regard, heart-on-chip (HOC) systems have been developed as a more efficient and cost-effective solution than traditional methods, such as 2D cell culture and animal models. HOCs must replicate the biology, physiology, and pathology of human heart tissue to be considered a reliable platform for heart disease modeling and drug testing. Therefore, many efforts have been made to find the best methods to fabricate different parts of HOCs and to improve the bio-mimicry of the systems in the last decade. Beating HOCs with different platforms have been developed and techniques, such as fabricating pumpless HOCs, have been used to make HOCs more user-friendly systems. Recent HOC platforms have the ability to simultaneously induce and record electrophysiological stimuli. Additionally, systems including both heart and cancer tissue have been developed to investigate tissue-tissue interactions' effect on cardiac tissue response to cancer drugs. In this review, all steps needed to be considered to fabricate a HOC were introduced, including the choice of cellular resources, biomaterials, fabrication techniques, biomarkers, and corresponding biosensors. Moreover, the current HOCs used for modeling cardiac diseases and testing the drugs are discussed. We finally introduced some suggestions for fabricating relatively more user-friendly HOCs and facilitating the commercialization process.

Low-tech vs. high-tech approaches in µPADs as a result of contrasting needs and capabilities of developed and developing countries focusing on diagnostics and point-of-care testing.

Paper-based analysis has captivated scientists' attention in the field of analytical chemistry and related areas for the last two decades. Arguably no other area of modern chemical analysis is so broad and diverse in its approaches spanning from simple 'low-tech' low-cost paper-based analytical devices (PADs) requiring no or simple instrumentation, to sophisticated PADs and microfluidic paper-based analytical devices (µPADs) featuring elements of modern material science and nanomaterials affording high selectivity and sensitivity. Correspondingly diverse is the applicability, covering resource-limited scenarios on the one hand and most advanced approaches on the other. Herein we offer a view reflecting this diversity in the approaches and types of devices. The core idea of this article rests in dividing µPADs according to their type into two groups: A) instrumentation-free µPADs for resource-limited scenarios or developing countries and B) instrumentation-based µPADs as futuristic POC devices for e-diagnostics mainly aimed at developed countries. Each of those two groups is presented and discussed with the view of the main requirements in the given area, the most common targets, sample types and suitable detection approaches either implementing high-tech elements or low-tech low-cost approaches. Finally, a socioeconomic perspective is offered in discussing the fabrication and operational costs of µPADs, and, future perspectives are offered.

A microfluidic device for enhanced capture and high activity release of heterogeneous CTCs from whole blood.

Circulating tumor cells (CTCs) are tumor cells that spontaneously detach from the primary focus, and early detection and characterization of CTCs is vital for cancer diagnosis and appropriate treatment. Current methods commonly use EpCAM to capture CTCs, but this results in a loss of information on other CTC subsets (EpCAM-negative cells) due to the heterogeneity of CTCs. Here, we report a novel microfluidic device that integrates the capture and release of heterogeneous CTCs directly from whole blood. A spiral chip was designed for the separation of differently sized cells, and larger CTCs were effectively separated from smaller blood cells with a 98% recovery rate. CD146-containing magnetic beads were used to complement the EpCAM-based CTC capture methods, and the capture efficiency of Fe3O4@Gelatin@CD146/EpCAM increased by 20% over Fe3O4@Gelatin@EpCAM. Finally, MMP-9 was employed to release CTCs with high efficiency and less damage by degrading gelatins on the surface of Fe3O4. The established method was successfully applied to CTC capture and release in a simulated patient's whole blood. The developed method achieved enhanced capture and high activity release of heterogeneous CTCs with less interference by blood cells, which contributes to the early detection and clinical downstream analysis of CTCs.

Evaluation of Barrier Integrity Using a Two-Layered Microfluidic Device Mimicking the Blood-Brain Barrier.

The blood-brain barrier (BBB) plays an essential role in maintaining the homeostasis of the brain microenvironment by controlling the influx and efflux of biological substances that are necessary to sustain the neuronal metabolic activity and functions. This barrier is established at the blood-brain interface of the brain microcapillaries by different cells. These include microvascular endothelial cells, astrocytes, and pericytes besides other components such as microglia, basal membrane, and neuronal cells forming together what is commonly referred to as the neurovascular unit; different in vivo and in vitro platforms are available to study the BBB where each system provides specific benefits and drawbacks. Recently, organ-on-a-chip platforms combine the elegance of microengineering technology with the complexity of biological systems to create near-ideal experimental models for various diseases and organs. These microfluidic devices with micron-sized channels allow the cells to be grown in a more biologically relevant environment, enabling cell to cell communications with continuous bathing in biological fluids in a tissue-like fashion. They also closely represent tissue and organ functionality by recapitulating mechanical forces as well as vascular perfusion. Here, we describe the use of humanized BBB model created with microfluidic organ-on-a-chip technology where human brain microvascular endothelial cells (BMECs) are cocultured with primary human pericytes and astrocytes. We thoroughly described the method to assess BBB integrity using a microfluidic chip and various sizes of labeled dextran as permeability markers. In addition, we provide a detailed protocol on how to microscopically investigate the tight junction proteins expression between hBMECs.

Numerical evaluation and experimental validation of fluid flow behavior within an organ-on-a-chip model.

BACKGROUND AND OBJECTIVE: By combining biomaterials, cell culture, and microfluidic technology, organ-on-a-chip (OoC) platforms have the ability to reproduce the physiological microenvironment of human organs. For this reason, these advanced microfluidic devices have been used to resemble various diseases and investigate novel treatments. In addition to the experimental assessment, numerical studies of biodevices have been performed aiming at their improvement and optimization. Despite considerable progress in numerical modeling of biodevices, the validation of these computational models through comparison with experimental assays remains a significant gap in the current literature. This step is critical to ensure the accuracy and reliability of numerical models, and consequently enhance confidence in their predictive results. The aim of the present work is to develop a numerical model capable of reproducing the fluid flow behavior within an OoC, for future investigations, encompassing the geometry optimization. METHODS: In this study, the validation of a numerical model for an OoC microfluidic device was undertaken. This comprised both quantitative and qualitative assessments of trace microparticles flowing through a physical OoC model. High-speed microscopy images of the flow, using a blood analog fluid, were analyzed and compared with the numerical simulations run using the Ansys Fluent software. For a qualitative analysis, the particles' paths through the inlet and bifurcations were observed whereas, for a quantitative analysis, the particle velocities were measured. Furthermore, oxygen transport was simulated and evaluated for different Reynolds numbers. RESULTS: In both qualitative and quantitative analyses, the results predicted by the numerical model and the ones outputted by the experimental model were in good agreement. These findings underscore the capability and potential of the developed numerical model. The examination of oxygen transport at various vertical positions within the organoid has revealed that for lower positions, oxygen transport predominantly occurs through diffusion, leading to a symmetric distribution of oxygen. Contrastingly, the convection phenomenon becomes more evident in the upper region of the organoid. CONCLUSIONS: The successful validation of the numerical model against experimental data shows its accuracy and reliability in simulating the fluid flow within the OoC, which consequently can expedite the OoC design process by reducing the need for prototypes' fabrication and costly laboratory experiments.

Investigating the Interaction Between Ice-Binding Proteins and Ice Surfaces Using Microfluidic Devices and Cold Stages.

Ice-binding proteins (IBPs) protect organisms living in sub-freezing conditions by inhibiting ice growth in fish and insects, limiting ice recrystallization in plants, and assisting bacteria to adhere to ice. The mechanisms by which these proteins bind to ice and inhibit its growth have been studied both experimentally and using molecular dynamic simulations. A unique experimental technique developed to test and characterize the interactions between IBPs and ice using a combination of a microfluidic device, cold stages with millikelvin temperature resolution, fluorescence-labeled IBPs, and fluorescence microscopy is described herein. The main advantage of this technique is the ability to exchange the solution around micron-sized ice crystals and characterize their binding to and inhibition of ice.

Biohybrid tongue based on hypothalamic neuronal network-on-a-chip for real-time blood glucose sensing and assessment.

The expression of sweet receptors in the hypothalamus has been implicated in energy homeostasis control and the pathogenesis of obesity and diabetes. However, the exact mechanism by which hypothalamic glucose-sensing neurons function remains unclear. Conventional detection methods, such as fiber photometry, optogenetics, brain-machine interfaces, patch clamp and calcium imaging, pose limitations for real-time glucose perception due to their complexity, cytotoxicity and so on. Therefore, this study proposes a biohybrid tongue based on hypothalamic neuronal network (HNN)-on-a-chip coupling with microelectrode array (MEA) for real-time glucose perception. Hypothalamic neuronal cultures were cultivated on a two-dimensional "brain-on-chip" device, enabling the formation of neuronal networks and electrophysiological signal detection. Additionally, we investigated the endogenous expression of sweet taste receptors (T1R2/T1R3) in hypothalamic neuronal cells, providing the basis for the biohybrid tongue based on HNN-on-a-chip's sweetness detection capabilities. The spike signal response to sucrose and glucose stimulation was detected, and concentration-dependent responses were explored with glucose concentrations ranging from 0.01 mM to 8 mM. MEAs allow for real-time recordings, enabling the observation of dynamic changes in neuronal responses to glucose fluctuations over time. The biohybrid tongue based on HNN-on-a-chip can measure various parameters, including spike frequency and amplitude, providing insights into neuronal firing patterns and excitability. Moreover, hypothalamic glucoregulatory neurons that sense and respond to changes in blood glucose was identified, including glucose-excited neurons (GE-Neurons) and glucose-inhibited neurons (GI-Neurons). The detection range for GE-Neurons spans from 0.4 to 6 mM, while GI-Neurons demonstrate sensitivity within the range of 1-8 mM. And the glucose detection limit was firmly established at 0.01 mM. Through non-linear regression analysis, the IC50 for GI-Neurons' spike firing was determined to be 4.18 mM. In conclusion, the biohybrid tongue based on HNN-on-a-chip offers a valuable in vitro tool for studying hypothalamic neurons, elucidating glucose sensing mechanisms, and understanding hypothalamic neuronal function.

A fully automated Lab-on-a-Disc platform integrated a high-speed triggered siphon valve for PBMCs extraction.

Human Peripheral Blood Mononuclear Cells (PBMCs) are isolated from peripheral blood and identified as any blood cell with a round nucleus that exhibits immune responses and undergoes immunophenotypic changes upon exposure to various pathophysiological stimuli. Obtaining high-recovery and clinical-grade PBMCs without decreasing cell viability and causing stress is crucial for disease diagnosis and successful immunotherapy. However, traditional manual PBMCs extraction methods rely on manual intervention with less recovery rate and reliability. In this study, we introduced a novel and efficient strategy for the fully automated extraction of PBMCs based on a Lab-on-a-Disk (LoaD) platform. The centrifugal chip used percoll as density gradient media (DGM) for separation and extraction on account of the density difference of cells in whole blood, without labeling and any additional extra cellular filtration or cell lysis steps. Above all, we proposed a high-speed triggered siphon valve, which was closed under the speed of cell sedimentation and subsequently opened by increasing speed to complete the extraction of PBMCs. It can avoid the problem that previous siphon valves rely on unstable hydrophilic surface treatment and prime under low/zero speed conditions. With valves and the clock channel integrated on the chip, users can achieve fully automated collection of PBMCs. Compared with the clinical laboratory results, the recovery rate of extracted PBMCs was 80 %. The experimental results prove that the high-speed triggered siphon valve improves the extraction efficiency of PBMCs. The robust chips, which are not only simple to manufacture and assemble but also stable and reliable to use, have great potential in biomedical and clinical applications.

Application of the fuzzy proportional integral differential (PID) temperature control algorithm in a liver function test system based on a centrifugal microfluidic device.

Clinical laboratory examinations frequently include biochemical analysis of the liver. The presence of alanine aminotransferase (ALT) and aspartate transaminase (AST) in serum can be used to identify liver damage. In this study, a centrifugal microfluidic-based clinical biochemical detection system was developed for the detection of liver function markers. Using the centrifugal microfluidic chip and centrifugal force on the chip, separation of blood cells and serum was performed. The extraction and mixing of quantitative serum and diluent were completed under the chip design of microchannels and microchambers. The lyophilized reagent beads in the chip interacted with the combined solution. The Fuzzy PID algorithm regulates the power of the heating film to deliver the ideal reaction temperature. In accordance with Beer-Lambert, the rate of change in the absorbance of the reaction solution at 340 nm of the light source was measured and a standard curve for the relationship between concentration and rate of change in absorbance was constructed. The system is portable, quick, and simple to use because it uses a centrifugal microfluidic chip instead of the conventional detection and analysis approach. In the future, it is anticipated that the system will have several applications in the detection of highly integrated on-chip point-of-care devices.

A portable microfluidic photometric detection method based on enzyme linked immunoscatter enhancement.

Currently, the combination of smart phones and microfluidic chips is a commonly used device for point-of-care testing (POCT) detection. Enzyme linked immunosorbent assay (ELISA) is an effective way to detect specific proteins in disease. Because the detection accuracy of smartphone cameras is difficult to directly replace high-precision spectral devices, the combination of smartphones and ELISA has not been widely used. Therefore, this paper proposes a microfluidic photometric detection method based on ELISA scattering enhancement. Firstly, the scattering characteristics of IMB are mined, and the optimal value of absorbance error compensation parameter is obtained. Secondly, the absorbance error compensation model based on scattering enhancement characteristics is established to improve the image acquisition accuracy of smart phones. Finally, the microfluidic photometric detection chip is developed, and the optical path system, optical path adjustment system and POCT detection App of smart phone are designed. The optimal compensation parameters of IMB were obtained based on simulated samples, and the linearity of absorbance and concentration increased by 22.6% after compensation. In the IL-6 sample experiment, the detection results of the platform in this paper had a good linear correlation with IL-6 sample concentration, and the linear correlation coefficient was above 0.95459. At the same time, the detection limit and accuracy meet the detection requirements. Therefore, with the participation of smart phones and microfluidic chips, problems such as difficult carrying and complex operation in traditional ELISA daily detection have been solved, laying a foundation for the future promotion and application of ELISA based POCT platform.

Direct competitive assay for HER2 detection in human plasma using Bloch surface wave-based biosensors.

The overexpression and/or amplification of the HER2/neu oncogene has been proposed as a prognostic marker in breast cancer. The detection of the related peptide HER2 remains a grand challenge in cancer diagnosis and for therapeutic decision-making. Here, we used a biosensing device based on Bloch Surface Waves excited on a one-dimensional photonic crystal (1DPC) as valid alternative to standard techniques. The 1DPC was optimized to operate in the visible spectrum and the biosensor optics has been designed to combine label-free and fluorescence operation modes. This feature enables a real-time monitoring of a direct competitive assay using detection mAbs conjugated with quantum dots for an accurate discrimination in fluorescence mode between HER2-positive/negative human plasma samples. Such a competitive assay was implemented using patterned alternating areas where HER2-Fc chimera and reference molecules were bio-conjugated and monitored in a multiplexed way. By combining Label-Free and fluorescence detection analysis, we were able to tune the parameters of the assay and provide an HER2 detection in human plasma in less than 20 min, allowing for a cost-effective assay and rapid turnaround time. The proposed approach offers a promising technique capable of performing combined label-free and fluorescence detection for both diagnosis and therapeutic monitoring of diseases.

Neuromuscular Junction-on-a-Chip for Amyotrophic Lateral Sclerosis Modeling.

Amyotrophic lateral sclerosis (ALS) is a progressive and degenerative disorder of the nervous system that can significantly reduce the physical activity of patients at the end stages. As the field of disease pathophysiology has advanced in recent years, studies have looked at the role of neuromuscular junction's dysfunctionality in ALS. In the past years, various in vitro and in vivo models were developed to scrutinize the underlying mechanisms of the disease and investigate the effects of candidate drugs, but the application of the developed models faced many challenges. Hence, the attentions shifted to cutting-edge technologies such as the organ-on-a-chip, which can mimic the pathophysiology of the disease as a special biological platform using patient-derived cells in the integration of engineering sciences to expand researchers' perspectives on the disease. In addition, organ-on-a-chip technology can reduce some of the challenges of using other in vitro and in vivo models, which can pave the way for other discoveries and advances in this disease.

Operando investigation of particle re-entrainment mechanism in electrostatic capture process on the lab-on-a-chip.

Inhalable particle is a harmful air pollutant that causes a significant threat to people's health and ecological environments, which should be removed to purify air, but there exists limited removal efficiency due to particle re-entrainment. Here, Operando observation system based on microscopic visualization method is developed to make in situ test of particle migration, deposition and re-entrainment characteristics on a lab-on-a-chip to achieve the investigation in micro-level scale. The deposition evolution of charged particles is recorded in electric field region intuitively, which confirms the fracture of particle chain occurs during the growth process of deposited particles. It captures the instantaneous process that a larger particle with micron size due to the coagulation of submicron particles fractures from main body of the particle chain for the first time. The analysis of migration behavior of a single submicron particle near electrode surface demonstrates the direct influence of drag force on the fracture of particle chain. This work is the first-time visualization of dynamic process and mechanism elucidation of particle re-entrainment at the micron level, and the findings will provide the theory support for the particle re-entrainment mechanism and bring inspires of enhancing capture efficiency of inhalable particle.

Cell-free fetal DNA (cffDNA) extraction from whole blood by using a fully automatic centrifugal microfluidic device based on displacement of magnetic silica beads.

The purpose of this research was to design a fully automated centrifugal microfluidic system (Lab-on-a-Disk) for isolating cell free fetal DNAs (cffDNAs) from whole blood. To achieve this goal, magnetic silica beads were used, such that after attaching cffDNA to them, they were transferred between chambers by using external fixed magnets. All the standards and required steps for cffDNA extraction including plasma separation, adding proteinase K, lysis buffer, binding buffer, washing buffer, and elution buffer were considered in this designed disk. To evaluate the function of the disk, the collected samples were tested from several aspects. First, the purity of extracted plasma from whole blood was investigated which included hemoglobin test, hemocytometer, etc. This disk could extract 1.3 mL pure plasma from 3 mL blood with 45% hematocrit. The results of the extracted plasma showed 99% purity. Finally, the cffDNAs were examined by using a male fetal gender identification kit and real-time PCR machine. The results indicated the correct function of the disk in extracting cffDNAs in samples of 10 Landa from cycle 34 onwards. Compared to the clinical method, the disk not only was able to extract cffDNA in 20 min but also it led to less buffer consumption since the disk only required 1 mL plasma for extraction of cffDNAs.

A novel PDMS-based digital magnetofluidic platform for lab-on-a-chip applications.

Superhydrophobic gold film embedded PDMS was employed as a novel platform for digital magnetofluidics. The device performance for lab-on-a-chip applications was investigated by demonstrating four types of reactions. First, acid-based titration was introduced as a simple mixing reaction. Second, colorimetric detection of phosphate based on the molybdenum blue method was represented as a more complicated reaction. The fabricated device was able to determine the amount of phosphate in the concentration range of 10-100 ppm with %RSD of color intensity of less than 5%. Third, colorimetric detection of glucose using glucose oxidase was demonstrated as an enzymatic reaction. A linear range of 1-20 mM for determination of glucose was applied for measuring glucose in beverages with recovery percentages of glucose in the acceptable range of 89.6-106.8%. Finally, multistep analysis of C-reactive protein (CRP) based on immunomagnetic separation was successfully demonstrated on this proposed device. Therefore, the superhydrophobic gold-coated PDMS has shown its ability to be a simple platform for digital magnetofluidics for a variety of applications in the field of lab-on-a-chip technology.

Therapeutic targeting of tumor spheroids in a 3D microphysiological renal cell carcinoma-on-a-chip system.

Metastatic renal cell carcinoma (RCC) remains an incurable disease for most patients highlighting an urgent need for new treatments. However, the preclinical investigation of new therapies is limited by traditional two-dimensional (2D) cultures which do not recapitulate the properties of tumor cells within a collagen extracellular matrix (ECM), while human tumor xenografts are time-consuming, expensive and lack adaptive immune cells. We report a rapid and economical human microphysiological system ("RCC-on-a-chip") to investigate therapies targeting RCC spheroids in a 3D collagen ECM. We first demonstrate that culture of RCC cell lines A498 and RCC4 in a 3D collagen ECM more faithfully reproduces the gene expression program of primary RCC tumors compared to 2D culture. We next used bortezomib as a cytotoxin to develop automated quantification of dose-dependent tumor spheroid killing. We observed that viable RCC spheroids exhibited collective migration within the ECM and demonstrated that our 3D system can be used to identify compounds that inhibit spheroid collective migration without inducing cell death. Finally, we demonstrate the RCC-on-a-chip as a platform to model the trafficking of tumor-reactive T cells into the ECM and observed antigen-specific A498 spheroid killing by engineered human CD8+ T cells expressing an ROR1-specific chimeric antigen receptor. In summary, the phenotypic differences between the 3D versus 2D environments, rapid imaging-based readout, and the ability to carefully study the impact of individual variables with quantitative rigor will encourage adoption of the RCC-on-a-chip system for testing a wide range of emerging therapies for RCC.

Bionanotechnology and bioMEMS (BNM): state-of-the-art applications, opportunities, and challenges.

The development of micro- and nanotechnology for biomedical applications has defined the cutting edge of medical technology for over three decades, as advancements in fabrication technology developed originally in the semiconductor industry have been applied to solving ever-more complex problems in medicine and biology. These technologies are ideally suited to interfacing with life sciences, since they are on the scale lengths as cells (microns) and biomacromolecules (nanometers). In this paper, we review the state of the art in bionanotechnology and bioMEMS (collectively BNM), including developments and challenges in the areas of BNM, such as microfluidic organ-on-chip devices, oral drug delivery, emerging technologies for managing infectious diseases, 3D printed microfluidic devices, AC electrokinetics, flexible MEMS devices, implantable microdevices, paper-based microfluidic platforms for cellular analysis, and wearable sensors for point-of-care testing.

Brain stimulation-on-a-chip: a neuromodulation platform for brain slices.

Electrical stimulation of ex vivo brain tissue slices has been a method used to understand mechanisms imparted by transcranial direct current stimulation (tDCS), but there are significant direct current electric field (dcEF) dosage and electrochemical by-product concerns in conventional experimental setups that may impact translational findings. Therefore, we developed an on-chip platform with fluidic, electrochemical, and magnetically-induced spatial control. Fluidically, the chamber geometrically confines precise dcEF delivery to the enclosed brain slice and allows for tissue recovery in order to monitor post-stimulation effects. Electrochemically, conducting hydrogel electrodes mitigate stimulation-induced faradaic reactions typical of commonly-used metal electrodes. Magnetically, we applied ferromagnetic substrates beneath the tissue and used an external permanent magnet to enable in situ rotational control in relation to the dcEF. By combining the microfluidic chamber with live-cell calcium imaging and electrophysiological recordings, we showcased the potential to study the acute and lasting effects of dcEFs with the potential of providing multi-session stimulation. This on-chip bioelectronic platform presents a modernized yet simple solution to electrically stimulate explanted tissue by offering more environmental control to users, which unlocks new opportunities to conduct thorough brain stimulation mechanistic investigations.

Efficacy of Mesenchymal-Stromal-Cell-Derived Extracellular Vesicles in Ameliorating Cisplatin Nephrotoxicity, as Modeled Using Three-Dimensional, Gravity-Driven, Two-Layer Tubule-on-a-Chip (3D-MOTIVE Chip).

Mesenchymal stromal cell (MSC)-derived extracellular vesicles (EVs) are known to have a therapeutic effect on nephrotoxicity. As animal models require significant time and resources to evaluate drug effects, there is a need for a new experimental technique that can accurately predict drug effects in humans. We evaluated the therapeutic effect of MSC-derived EVs in cisplatin nephrotoxicity using a three-dimensional, gravity-driven, two-layer tubule-on-a-chip (3D-MOTIVE chip). In the 3D-MOTIVE chip, 10 µM cisplatin decreased the number of attached cells compared to the vehicle. Conversely, annexin V and reactive oxygen species (ROS) were increased. Cell viability was increased 2.8-fold and 2.5-fold after treatment with EVs at 4 and 8 µg/mL, respectively, compared to the cisplatin-induced nephrotoxicity group. Cell attachment was increased 2.25-fold by treatment with 4 µg/mL EVs and 2.02-fold by 8 µg/mL EVs. Annexin V and ROS levels were decreased compared to those in the cisplatin-induced nephrotoxicity group. There were no significant differences in annexin V and ROS levels according to EV concentration. In sum, we created a cisplatin-induced nephrotoxicity model on a 3D-MOTIVE chip and found that MSC-derived EVs could restore cell viability. Thus, MSC-derived EVs may have the potential to ameliorate cisplatin-induced nephrotoxicity.

A fully 3D-printed versatile tumor-on-a-chip allows multi-drug screening and correlation with clinical outcomes for personalized medicine.

Optimal clinical outcomes in cancer treatments could be achieved through the development of reliable, precise ex vivo tumor models that function as drug screening platforms for patient-targeted therapies. Microfluidic tumor-on-chip technology is emerging as a preferred tool since it enables the complex set-ups and recapitulation of the physiologically relevant physical microenvironment of tumors. In order to overcome the common hindrances encountered while using this technology, a fully 3D-printed device was developed that sustains patient-derived multicellular spheroids long enough to conduct multiple drug screening tests. This tool is both cost effective and possesses four necessary characteristics of effective microfluidic devices: transparency, biocompatibility, versatility, and sample accessibility. Compelling correlations which demonstrate a clinical proof of concept were found after testing and comparing different chemotherapies on tumor spheroids, derived from ten patients, to their clinical outcomes. This platform offers a potential solution for personalized medicine by functioning as a predictive drug-performance tool.