دستاوردهای اخیر کشور در حوزه سامانه‌های ریز مقیاس زیستی

Small scale robots have significant promise for advancing medical diagnosis and treatment because of their unique ability to move and perform complex tasks at small scales. Due to high importance of the magnetic small-scale robots and their great potential for the biomedical applications, they attracted a lot of attention during recent years. In this presentation, we introduce the field of micro/nano robotics, particularly magnetic small robots, and review their biomedical applications in diagnosis, microsurgery, targeted drug delivery, bio sampling, and wound healing. Also some of recent projects of Sharif Micro/Nano Robotics (SMNR) Laboratory are presented.

The advancements in nanotechnologies, computer programming, and consumer electronics have allowed the development of mobile health diagnostics with applications in disease detection and treatment monitoring at the point-of-care. Metal nanoprobes and self-propelling nanoparticles possess unique catalytic properties that can be utilized in the development of mobile health diagnostics by seamlessly integrating with the advancements in smartphone-based image processing and machine learning. Amongst the advantages of catalytically-powered nanomotors and nanoprobes are its simplicity in signal amplification, its stability over time, and easy integration with portable devices such as smartphones. We have developed multiple smartphone-based diagnostic systems by utilizing intrinsic catalytic properties of metal nanoparticles and on-phone deep learning-based image processing. Our unique approach of optical signal amplification through micro- or macro-sized gas bubble formation combined with accurate and rapid on-phone deep learning-based image processing allows the development of simple, low-cost virus detection using a smartphone camera with and without using any smartphone-based optical hardware attachment. We have been able to detect both intact viruses and nucleic acids in complex biological samples. In those scenarios where we targeted nucleic acids, we integrated loop-mediated isothermal amplification (LAMP) or clustered regularly interspaced short palindromic repeats (CRISPR) with our catalytically-powered nanomaterials for bright-field optical sensing. We also employed adversarial neural networks to enhance the adaptability of our platform technology for the detection of different viruses by leveraging a retrospective dataset of smartphone-taken microfluidic chip photos to create on-demand image classifiers for target pathogens. We have evaluated the performance of our developed catalytically-powered diagnostic systems with hundreds of patients samples with different viral infections such as HIV, HBV, HCV, ZIKV, and SARS-CoV-2.

Wearable electronic sensors are an integral part of digital health. An efficient sensor needs to be optimized for cost and accuracy. Use of the emerging Machine Learning algorithms is a great step forward to design accurate sensors. Nevertheless, power consumption, mobile data offloading, and processing time are important chalenges that must be addresses in the design of any commercial device for Digital Health. In this talk, the sensors developed in Biosen Group, in Electrical Engineering Dept. of Sharif University of Technology are discussed including: Smart watch for health monitoring, ECG patch for Heart Arrhythmia Detection, Human Stress Sensor, Elderly Fall Detection, and Digital Stethoscope. The idea behind the design of these sensors is to use off-the-shelf integrated circuits with the state-of-the-art Machine Learning (ML) and Artificial Intelligence (AI) algorithms to detect disease or abnormal situations, in a reasonable time with an affordable cost. The comfort of the user and the non-invasive performance are two key issues considered in the design of these sensors.

Microfluidic technologies have paved the way for miniaturization and automation of analytical protocols, enabling development of integrated point-of-care devices for early-stage diagnosis of diseases. Recently, Lab-on-a-Disc (LoD) technology (so called centrifugal microfluidics), has gained a considerable attention due to its unique features. In this system, a configuration, consisting of chambers and channels, is mounted on the surface of a disc, and the liquid is transferred through it by means of rotational forces generated by the centrifugation. This system has its intrinsic governing forces including Coriolis force, Euler force, and most importantly Centrifugal force, that is easily accessible using a motor and decreases the number of required physical connections or pumps used in a typical microfluidic platform. This advantage brings this technology closer to producing commercial products in the form of point of care testing (POCT) systems. In this talk, I will present my group recent effort in design and manufacturing centrifugal microfluidic disks by application in blood analysis such as WBC’s lysis and DNA extraction, different biomarkers detection (hemoglobin and hemoglobin A1c), and cfDNA extraction from plasma.

Rapid, simple, inexpensive and on-site measurement of species is one of the demands of today’s societies and human industrial life. Biosensors, as small and portable devices with simple operatory, can be a response to such a need. These devices are generally composed of three parts: a sensing element, a transducer, and a signal processor. They can be designed for many industrial, environmental, agricultural, biological, pharmaceutical and clinical applications. Biosensors are in fact sensors in which a biological process is responsible for the signal production. From the invention time to now, numerous biosensors have been designed for fast determination of biological important species which some of them were even commercialized. Nowadays, by progress in sciences and technologies, and by expanding the interdisciplinary collaborations, the number of biosensors which find a chance to be commercialized and enter the market are growing fast. Their applications in clinical medicine for determination of biomarkers for early diagnosis and screening or in managing a disease through point-of-care devices show their importance. However, the main challenges in designing biosensors are decreasing the limit of detection, increasing the sensitivity and accuracy of an analysis, increasing life-time and miniaturization ability which is very vital for placing them on lab-on-chip. Also, scientists are now trying to develop sensitive biosensors for non-invasive measurements of biomarkers in other biological samples of the body like breath, sweat, saliva or tears instead of blood. Finding a proper biomarker for the detection of disease in humans, animals, and even plants are the first challenge and then designing a suitable biosensor for that biomarker is the second challenge which can be solved to some extent by integration of various scientific disciplines.

Despite noteworthy developments in tumor therapy, cancer is still one of the main reasons for death worldwide. While present cures supply hopeful marks, they trigger harsh cytotoxicity, with limited success in preventing and recurrence of the disease. To overcome the mentioned issues, implantable biomaterials have been developed as promising systems for the local delivery of therapeutic agents to cancerous tissues. Due to the unique characteristics of biocompatible polymers, they have been used in different approaches of localized drug delivery to ensure accurate control over the release of chemotherapy drugs, genes, proteins, and peptides. In this presentation, the recent progress in stimuli-responsive implantable drug delivery systems for preventing tumor recurrence and suppressing tumors are reported. In particular, I pay to redox-, enzyme-, and pH-responsive systems in programmable drug delivery and the near-infrared-, ultrasound-, electric-, and magnetic-regulated release in on-demand local drug delivery systems. The preparation process, physicochemical characteristics of implantable materials, and kinetic models of the drug release from these platforms are also discussed in detail.

In this lecture, design methods for microfluidic chips are discussed. The aim is to share some fundamental rules that governs the separation efficiency, throughput and viability. Specific case studies including dielectrophoresis and spiral microfluidics are presented. In addition, designs and simulation results that uses cell inherent motion are also discussed. In the final part of the lecture, feasible particle detection and tracking techniques are discussed. The audience have the time to ask their questions and propose suggestions regarding the presented materials.

As the building block of our bodies, cells play a crucial role in research laboratories to develop any kind of product in medicine. It is believed that isolation of cells from the body and cultivation of cells in vitro changes cells' function in gene and protein expressions. About 50 years ago, it was reported that the original spherical morphology of chondrocytes is altered to the spindle fibroblast-like morphologies after isolation from hyaline cartilage. In addition, the expression of collagen type II is changed to collagen type I. Therefore, many types of research are conducted to provide a similar condition to the natural environment in vitro. We introduced cell imprinting as a physical method to mimic the natural shape of cells in vitro. In this method, cells are considered as mold, and polymeric materials replicate their shape. The replicated construct is used as a substrate for the cultivation of cells. The cell imprinting method can provide a bio-imitated environment for regulation of cell function and maintain the original phenotype of cells in vitro. Moreover, it has been proved that cell imprinted substrates can induce chondrogenic, osteogenic, tenogenic, keratinogenic, myogenic, neurogenic and Schwann cell differentiation signals in cells both in vitro and in vivo. Recently, we analyzed the nano-scale topographies of different cells and found that each cell has its own fingerprint on the replicated substrate. It seems that in the near future, the conventional polystyrene-based tissue culture plates will be substituted with substrates with physical-chemical properties similar to the cell microenvironment to regulate cell fate.

Since the introduction of droplet-based microfluidics, the manipulation of droplets within microfluidic-droplet-generation devices has provided opportunities for various applications such as drug and growth factor encapsulation, nutrition delivery control, single-cell analysis, cell culturing, and material synthesis. Various methods concerning microdroplet generation have been introduced based on the organization of multiphase fluid flow with respect to designed geometry, in which three of the most popular designs are T-junction, flow-focusing, and co-flowing. In such microdevices, shear and pressure forces cause the continuous phase to squeeze the dispersed phase and split up the droplets due to their immiscibility. Well-designed droplet-based microfluidic devices facilitate the ability to produce highly monodispersed droplets with high controllability over the frequency. Capability in controlling the size, morphology, chemical composition, spatio-temporal regulation of the produced microcapsules are their unprecedented features for shifting away from traditional arduous clinical and biological assays to more compact and mobile microdevices. Herein, we report microfluidically generated microgels containing VEGF-conjugated fluorescent carbon dots (CDs) for imaging-monitored tracking of VEGF delivery to ischemic muscles as an example of droplet-based microfluidics.

The presentations will provide an overview about the use of microfluidics for drug development and drug testing, in particular for the production of various nanodrug carriers. Various methods for the production of nano carriers particularly for mRNA vaccines will be discussed and the role of microfluidics as a paradigm-shifting approach will be explained. Finally, Dr. Mousavi Shaegh will explain the technologies that have been developed in his research group for the production of lipid nano particles (LNP) for Covid-19 vaccine delivery.

Circulating tumor cells (CTCs) carry crucial information on primary tumors critical for improving precise cancer treatment monitoring according to NCCN (national comprehensive cancer network) guidelines. Numerous microfluidic platforms have been developed in the last few years to isolate these rare cells in the patient bloodstream for monitoring treatment. However, the practical method would need for a clinical application that is low cost, simple and efficient. Herein, we demonstrate a novel microarray-based microfluidic device that consumes the lowest materials and volume and can work with real blood with the lowest manipulation. The key novelty of this approach lies in the optimum and new geometry of pillar arrays in the chip flow components for reducing its size and volume and increasing capture efficiency. Therefore, the device makes us suitable for clinical applications. Our device is developed with the optimized channel geometries and flow rate, the capture efficiency reached >90% with a purity of >82% when capturing spiked tumor cells in the buffer. The capture efficiency of >90% has been achieved for Rhomboid and Rectangular pillars using spiked cancer cells in whole blood from a healthy donor. The presented platform shows great promise for precise CTC enumeration, drug and biological evaluations of CTCs, and cancer metastasis, as well as for monitoring the cancer treatment.

Point-of-care testing (POCT) is a test method performed on the sampling site or patient bedside. Clinicians have relied upon lateral flow assays (LFAs) since the 1970s for diagnostic testing. The efficacy of dipstick assays goes back even earlier, to the 1940s. Immunochromatography (or lateral flow tests) combines separation of the sample molecules and reagents based on migration on a solid support by capillary flow and the identification and detection procedures are based on the antigen–antibody immune reaction. A typical lateral flow test format usually consists of a nitrocellulose or filter paper membrane that carries the liquid sample from the application pad via the conjugate release pad (e.g., labeled antibodies), along a strip. When an immunocomplex with the immobilized detection antibody is formed, if colloidal gold or latex particles are used as conjugates, a red-purple or blue line, respectively, is generated. Migration of the samples through the membrane is rapid (i.e., 5–15 min), which provides for rapid detection of the antigen in question. Further advantages of immunochromatography are the low sample volume, portable devices, and generally no need for extra-large and expensive equipment. More accurate results can be achieved rapidly by the application of portable analytical instruments and compatible reagents. It has been widely used in the field of in vitro diagnosis (IVD). Paper-based microfluidics technology has great potential in developing POCT due to its advantages in low cost, disposable, widely available, ease of safe handling, hydrophilic quality, and biocompatibility with most samples, simple operation, rapid detection, portable equipment and unrestricted application conditions which lend themselves to the mass production of POCT devices. Such paper-based devices incorporate materials such as cellulose or nitrocellulose. In recent years, the development of paper-based microfluidic technology and its integration with various new technologies and methods have promoted the substantial development of POCT technology and methods. Some other components are such as sample application pad, conjugate pad, substrate (nitrocellulose) membrane and adsorbent pad. In recent pandemic about 1 in 3 people with COVID-19 do not have symptoms but can still infect others. Rapid tests help to check if someone has COVID-19. If people test positive and self-isolate, it helps stop the virus spreading. Research shows rapid tests are a reliable test for COVID-19. They give a quick result and do not need to be sent to a lab.We in Tarbiat Modares University, Tehran have developed a rapid antigen and antibody test in which homemade reagents were used. These tests enjoy a 97 % sensitivity and 99 % specificity and presently are marketed by Rojan Azma mfg ,used in COVID-19 spread control in the national level as well as some neighboring countries .Nano gold particles are used in these assays for detection and visualization proposes .The average performance time is 15 minutes including nasopharyngeal sample collection and assay development .These assays are easily performed in field and are inexpensive as well as easy to handle by nonprofessional health workers or even the patient self-check.

Examining the tumor's margins during surgery for breast cancer patients is crucial to ensure the definitive removal of suspicious and high-risk cells with minimal damage to healthy tissue. The remanence of cancer cells in the body causes resurgeries and inevitable postoperative treatments, with many side effects. Frozen pathology of tumor margins during surgery is a conventionally accepted method to guide the surgeon during the operation. However, the time-consuming and inaccurate process of margin examination, along with 20 to 70% false negative, are limitations in evaluating margins by frozen pathology during surgery. Cancer Diagnostic Probe (CDP) was developed for the first time based on the real-time electrochemical measurement of the metabolism of hypoxia glycolysis and Reverse Warburg effect in precancerous and cancer cells during the surgery. CDP system with several US patents (US 11,179,076 B2, US 10,786,188 B1, US 11,179,077 B2, US 11,181,499 B2) and published ISI articles in the journals of bioengineering and translational medicine (https://doi.org/10.1002/btm2 .10236), International Journal of Medical Robotics and Computer Assisted Surgery (https://doi.org/10.1002/rcs.2335), Biosensors and Bioelectronics (https://doi.org/10.1016/j.bios.2020.112209), and License number 23212882 from the Ministry of Health is introduced as a surgical assistance system in breast cancer. In case of availability of frozen pathology, CDP is used as a complementary device, and in the absence of frozen pathology, it is used as a surgical assistance system to check the cavity-side margins. The new system uses a needle sensor to reveal the area of suspected cancerous margin inside the body (cavity-side margin) within a few millimeters in 30 seconds. This system has a clinical diagnostic classification corresponding with the pathological results of the tested tissues and the CDP response peaks, based on the classification of the pathological system (Ductal intraepithelial neoplasia (DIN), Lobular intraepithelial neoplasia (LIN), and Fibro epithelial lesion (FEL) (according to the latest reported revisions)) . The main part of CDP is electrically active carbon nanotubes decorated needle sensors. Functionalized CNTs are crucial in selective sensing of ROS released from cancer cells during glycolysis. The unique ability to instantly and non-invasively examine internal margins with pathological values (from benign and high-risk masses to pre-invasive and invasive cancerous lesions) makes CDP a distinctive surgical instrument with portable and straightforward equipment to increase the accuracy of cancer cells diagnosis in patients, candidates for breast cancer surgery.

The private and public health providers are under extreme pressure to deliver effective patient care at the right point in the care pathway. During COVID-19 pandemic, the importance of POC testing devices has been enhanced. Point of care testing (POCT) has the power to disrupt traditional pathways and support improved patient outcomes as well as wellness. Moreover, early and rapid results out of accessible and affordable POCTs significantly cause the higher quality of life with a certain healthcare expenditure. In comparison to medical devices and pharmaceuticals, investing on IVD will pays back much more efficiently. But several challenges exist such as POCT Connectivity, POCT Regulations, Multiple Device Types & Capabilities and Operator Certifications. To pave the way, Stakeholder matrix from patient to regulatory should be considered.

Microfluidic devices have received wide attention and shown great potential in the field of tissue engineering and regenerative medicine. Investigating cell response to various stimulations is much more accurate and comprehensive with the aid of microfluidic devices. In this study, initially, we introduce a microfluidic device by which the matrix density as a mechanical property and the concentration profile of a biochemical factor as a chemical property could be altered. This microfluidic device is capable of mimicking both 2D to 3D and 3D to 3D migration of different types of cells. Fluid shear stress is negligible on the cells and a stable concentration gradient can be obtained by diffusion. The device was designed by a numerical simulation so that the uniformity of the concentration gradients throughout the cell culture chamber was obtained. Neural stem cells (NSCs) were cultured within varying collagen matrix densities while exposed to NGF concentrations and they experienced 3D to 3D collective migration. Also, adult neural cells were cultured within this device and they showed different branching and axonal navigation phenotypes within varying nerve growth factor (NGF) concentration profiles. Next, by generating vascular endothelial growth factor (VEGF) concentration gradients, adult human dermal microvascular endothelial cells (HDMVECs) were also migrated in a 2D to 3D manner and formed a stable lumen within a specific collagen matrix density. It was observed that a minimum absolute concentration and concentration gradient was required to stimulate migration of all types of the cells. This device has the advantage of changing multiple parameters simultaneously and is expected to have wide applicability in cell studies. In another study, we formed colon cancer tumor spheroids of HT-29 cells using a microfluidic droplet generation method and in the next step, the viability test was performed using a live-dead cell assay. This device will be used in drug screening of tumor vasculature to recapitulate the three-dimensional microenvironment that cells reside in in vivo, where cells communicate with other cells and extracellular matrix.

Droplet generation technologies have seen an increased uptake in the food and health industry. The is mainly due to the synergy of devices that optimize chemical reactions, with those in which the biological responses to such compounds. For example, in pharmaceutical industry, the increasing prevalence of these droplet generator systems has been a result of the spiralling costs associated with drug development and screening. pharmaceutical compound takes more than 10 years and $2.5 billion to be brought to the market . The efforts have been focused on building instruments that can generate pico-to-nano droplet sizes with high throughput and high monodispersity. The common methods appreciated in such applications for generation of droplets on demands have been inkjet printing and microfluidics. Due to the limitation of such methods in producing droplets from different materials, continuous phases are often engineered to have physical properties satisfying the requirements of these systems. For example, for inkjet printing, the drop detachment is governed by the Rayleigh-Plateau instability which involves a involves a strong coupling between interfacial and viscous forces. To ensure successful droplet ejection, the ink composition and printing parameters must be precisely tuned within a narrow printing window to balance the interplay of these force. Therefore, despite its high resolution (10µm droplets), contactless deposition, and high drop generation rates (1 to100 kHz) , inkjet printing is well suited only for patterning low viscosity inks (roughly between 10 to 100 times higher than the viscosity of water. To print more viscous inks, the viscosity of the ink is carefully pre-treated to place this narrow window of physical properties, either by using thermal process or solvent dilution. Producing simple or double emulsions technologies have shifted toward the microfluidic devices as they provide a carrier medium with an exquisite monodispersity. The generation of emulsions of droplets with the diameter from 20µm to 500µm mandates a versatile scalable device that could generate droplets of prescribed rate and prescribed volume of a broad range of materials. Here in this talk we review the recent progress on the production of single and double emulsion with the focus on microfluidic techniques. We specifically address the current challenges for the scale up and also the opportunities for future works.

Nucleic acid biomarkers serve as the most reliable and specific targets for molecular detection. However, because of low copy number of these biomarkers and to increase sensitivity, amplification of them is applied. The challenge of using isothermal amplification systems as an alternate to the most extensive and laborious PCR-based amplification of nucleic acids has arisen recently. The main advantage of isothermal amplification is no requirement for expensive laboratory equipment for thermal cycling. Considerable efforts have been made to improve the current techniques of nucleic acid amplification and the development of new approaches based on the main drawbacks of each method. The most important and challenging goal was to achieve a low-cost, straightforward system that is rapid, specific, accurate, and sensitive.

Visual detection, as a universal sensing approach, holds great promise in various fields such as environmental monitoring, food safety, security issues, clinical and point-of-care diagnosis, and healthcare assays in especially resource-constrained areas, where sophisticated instrumentation may not be available. Many efforts have been made over the past few decades to develop optical probes which can be classified into two main groups: colorimetric and fluorometric approaches. In the former, changes in the absorption signal or wavelength is assigned to the concentration of an analyte whereas in the latter, changes in the emission characteristics is monitored for quantification. In either of these analytical signal modes, implementation of nanostructures can greatly enhance sensing. Owing to the high extinction coefficient of plasmonic nanoparticles together with their size, shape and environment dependent absorption profiles, they provide much better colorimetric probes compared to their conventional counterparts. Similarly, it has been shown that emitters in nanoscale such as quantum dots, nanoclusters and metal organic framework materials with incredible and tunable emission properties, have recently attracted great attention in the fields of sensing and bioimaging. Moving from single optical probes towards cross-reactive sensor arrays enables the recognition and discrimination of groups of target species. In array-based sensors, instead of relying on a specific lock and key interaction for sensing, an array of semi-selective sensor elements is used. These cross-reactive sensor elements provide differential responses and generate measurable fingerprint patterns which are analyzed by pattern recognition methods in order to classify the data and to detect unknown samples. Since the large amount of data provided in a sensor array usually has a high dimension and cannot be analyzed by basic calibration methods, a multivariate data reduction method is required to reduce the dimension of the data and to make it better visually interpretable.
In this presentation, basic principles in the design of nanostructure-based optical sensor arrays will be outlined. Focusing on our recent research in this field , we will present several examples of luminescent and plasmonic nanoparticles that have been used to produce the desired assembly of sensor elements for detection and discrimination of important analytes.

Infertility is on the rise worldwide, affecting almost 15% of couples (over 48 million couples). In nearly half of the cases, male-related issues such as low sperm count or poor motility are responsible for the infertility issue. Assisted reproductive technologies (ART) have been developed and refined over 40 years to treat infertility. ARTs include intrauterine insemination (IUI), in vitro fertilization (IVF), and intracytoplasmic sperm injection (ICSI), in which a selected subpopulation of high-quality sperm is either introduced closer to the egg or injected directly into the egg to achieve fertilization. However, one of the major concerns about ART, and ICSI, is that they bypass almost all the natural selection barriers that sperm encounter in vivo. The selection of high-quality sperm is crucial to infertility treatment. The success rate of the ART treatment cycle and embryo development rate are both directly correlated with the quality of the selected sperm. Swim-Up (SU) and Density Gradient Centrifugation (DGC) are the two most commonly used clinical methods for selecting high-quality sperm. These methods are time-consuming, labor-intensive, highly subjective, and they introduce sperm DNA damage due to centrifugation while also resulting in relatively low recovery rates. It is crucial to develop new methods for rapid, automated, and non-invasive selection of high-quality sperm by mimicking the natural selection process in vivo, ultimately improving the ART outcome. Bio-MEMS has emerged as a rapid and automated platform for cell separation and studying gamete function, capable of providing geometrically confined microenvironments that closely mimic the natural in vivo environment. In this presentation, we will study the application of Bio-MEMS in ART.

In this presentation, a label-free method for detection of the biomolecules including virus RNA/DNA in nasopharyngeal swab samples is reported. The presented method does not need any purification step and multiplication of the target which simplifies and expedites the analysis process. The kit consists of a textile which is agitated with liquid crystals (LC) and placed in a crossed polarized microscopy. The swab samples are placed on the LCs. In the presence of a particular biomolecule, the direction of LCs changes locally based on the properties of the biomolecule and forms a particular pattern. This method was examined for SARS-CoV2 virus. It could differentiate negative and positive SARS-CoV2 samples with an accuracy of 96% and also differentiated SARS-CoV2 from influenza types A and B with an accuracy of 93%. The kit is portable, simple to manufacture, convenient to operate, cost-effective, rapid and sensitive. The simplicity of the specimen processing, the speed of image acquisition, and fast diagnostic operations enable the deployment of the proposed technique for performing extensive on-spot screening of COVID-19 in public places.

Recent advances in microfabrication technologies have enabled us to construct collagen gel microbeads, which can be cultured with hepatocytes. However, little is known about the hepatocyte–collagen gel microbead interactions. Here, we aimed to clarify the effects of the balance between cell–cell and cell–collagen gel microbead interactions on hepatocyte morphogenesis and functions. The magnitude of cell–microbead interactions was controlled by changing the size of the microbeads, which were smaller than, comparable to, and larger than hepatocytes. These small, medium, and large microbeads were cultured separately with primary hepatocytes. Phase-contrast and time-lapse imaging revealed that the medium microbeads significantly induced the construction of 3D structures composed of the microbeads and hepatocytes in a self-organizing manner, whereas hepatocytes formed 2D monolayers with the small or large microbeads. These results suggest that only the medium microbeads induced the 3D tissue formation of hepatocytes. Furthermore, liver-specific functions, such as albumin secretion and ammonia clearance, were significantly upregulated in the 3D structures. These findings are critical to understand how to control the construction of 3D hepatocyte tissues with hydrogel microbeads in the context of biofabrication.

Watching LNPs smoothly coming out of the micromixer may surprise the engineering/science team and appear to them: oh God, we are done! we made the mRNA-Vaccine! But this is not the whole story, at least not for us!: 1- The whole process should be done “back to back” till the vaccine comes out of the device in the final vessels and packed! The only step that can be done after is labelling (even the latter is not much recommended). This mandate ensures, a p-value of less than 0.05, in all statistical analysis of the parameters; PDI < 0.8: normal requirements: 0.2, for a uniform size in 25 nm 95%of liposome product). 2- Throughputs less than 10 l/h from one single set-up does not work: do not buy headache (friendly advice ;D) 3- In simple words: the main challenge is Throughput and Filtration to the final product! The minor challenge is the design of a uniform wave-head diffusive micromixer with self-impinging flux which is not necessarily turbulent or chaotic. The remaining job is to design the hydro-fluidic network, capable of constant flow (resistant independent) network and put enough gages and high sampling rate control system. All in all, interesting and amazing challenge. In this seminar Dr. Asiaei will briefly review the scientific basis and main challenges involved in microfluidic holistic production of lnp based drugs.

Ali Mohammad Soltani: Head of Converging Technologies Policy Center
Mohammad Reza Movahedi: Vice President for Research and Technology, Sharif University of Technology