Blood biochemical indicators are an important basis for the diagnosis and treatment by doctors. The performance of related instruments, the qualification of operators, the storage method and time of blood samples and other factors will affect the accuracy of test results. However, it is difficult to meet the clinical needs of rapid detection and early screening of diseases with currently available methods. Point-of-care testing (POCT) is a new diagnostic technology with the characteristics of instant, portability, accuracy and efficiency. Microfluidic chips can provide an ideal experimental reaction platform for POCT. This paper summarizes the existing detection methods for common biochemical indicators such as blood glucose, lactic acid, uric acid, dopamine and cholesterol, and focuses on the application status of POCT based on microfluidic technology in blood biochemistry. It also summarizes the advantages and challenges of existing methods and prospects for development. The purpose of this paper is to provide relevant basis for breaking through the technical barriers of microfluidic and POCT product development in China.
Humans ; Point-of-Care Testing ; Lactic Acid/blood* ; Microfluidic Analytical Techniques/methods* ; Blood Glucose/analysis* ; Point-of-Care Systems ; Blood Chemical Analysis/instrumentation* ; Uric Acid/blood* ; Cholesterol/blood* ; Dopamine/blood* ; Microfluidics/methods*

As prepubertal boys do not yet produce spermatozoa, they cannot rely on sperm cryopreservation for fertility preservation before gonadotoxic therapy, such as high-dose alkylating agents or radiotherapy in the case of childhood cancers. According to the current guidelines, cryopreservation of testicular biopsies containing spermatogonial stem cells (SSCs) may be proposed to high-risk patients for potential later therapeutic use to fulfill the patients' wish for a biological child. One promising technique for human in vitro spermatogenesis and in vitro propagation of human SSCs is microfluidic (MF) culture, in which cells or tissues are subjected to a continuous flow of medium. This provides exact control over such parameters as nutrient content and gradients, as well as the removal of waste metabolites. While MF has been shown to maintain tissues and cell populations of organs for longer than conventional in vitro culture techniques, it has not been widely used for testicular in vitro culture. MF could advance human testicular in vitro culture and is also applicable to reprotoxicity studies. This review summarizes the findings and achievements of testis-on-chip (ToC) setups to date and discusses the benefits and limitations of these for spermatogenesis in vitro and toxicity assessment.
Humans ; Male ; Spermatogenesis/physiology* ; Testis/cytology* ; Cryopreservation ; Cell Culture Techniques/methods* ; Microfluidics/methods* ; Animals

OBJECTIVES: To synthesize a temperature-responsive multimodal motion microrobot (MMMR) using temperature and magnetic field-assisted microfluidic droplet technology to achieve targeted drug delivery and controlled drug release. METHODS: Microfluidic droplet technology was utilized to synthesize the MMMR by mixing gelatin with magnetic microparticles. The microrobot possessed a magnetic anisotropy structure to allow its navigation and targeted drug release by controlling the temperature field and magnetic field. In the experiment, the MMMR was controlled to move in a wide range along a preset path by rotating a uniform magnetic field, and the local circular motion was driven by a planar rotating gradient magnetic field of different frequencies. The MMMR was loaded with simulated drugs, which were released in response to laser heating. RESULTS: Driven by a rotating magnetic field, the MMMR achieved linear motion following a predefined path. The planar gradient rotating magnetic field controlled circular motion of the MMMR with an adjustable radius, utilizing the centrifugal force generated by rotation. The drug-loaded MMMR successfully reached the target location under magnetic guidance, where the gelatin matrix was melted using laser heating for accurate drug release, after which the remaining magnetic particles were removed using magnetic field. CONCLUSIONS The MMMR possesses multimodal motion capabilities to enable precise navigation along a predefined path and dynamic regulation of drug release within the target area, thus having great potential for a wide range of biomedical applications.
Drug Delivery Systems/methods* ; Temperature ; Drug Liberation ; Magnetic Fields ; Robotics ; Gelatin/chemistry* ; Delayed-Action Preparations ; Microfluidics ; Motion

Droplet microfluidics technology offers refined control over the flows of multiple fluids in micro/nano-scale, enabling fabrication of micro/nano-droplets with precisely adjustable structures and compositions in a high-throughput manner. With the combination of proper hydrogel materials and preparation methods, single or multiple cells can be efficiently encapsulated into hydrogels to produce cell-loaded hydrogel microspheres. The cell-loaded hydrogel microspheres can provide a three-dimensional, relatively independent and controllable microenvironment for cell proliferation and differentiation, which is of great value for three-dimensional cell culture, tissue engineering and regenerative medicine, stem cell research, single cell study and many other biological science fields. In this review, the preparation methods of cell-loaded hydrogel microspheres based on droplet microfluidics and its applications in biomedical field are summarized and future prospects are proposed.
Hydrogels/chemistry* ; Microfluidics/methods* ; Microspheres ; Regenerative Medicine ; Tissue Engineering/methods*

Objective To examine the antiplatelet effect of ticagrelor by microfluidic chip and flow cytometry under shear stress in vitro. Methods Microfluidic chip was used to examine the effect of ticagrelor on platelet aggregation at the shear rates of 300/s and 1500/s.We adopted the surface coverage of platelet aggregation to calculate the half inhibition rate of ticagrelor.The inhibitory effect of ticagrelor on ADP-induced platelet aggregation was verified by optical turbidimetry.Microfluidic chip was used to construct an in vitro vascular stenosis model,with which the platelet reactivity under high shear rate was determined.Furthermore,the effect of ticagrelor on the expression of fibrinogen receptor (PAC-1) and P-selectin (CD62P) on platelet membrane activated by high shear rate was analyzed by flow cytometry. Results At the shear rates of 300/s and 1500/s,ticagrelor inhibited platelet aggregation in a concentration-dependent manner,and the inhibition at 300/s was stronger than that at 1500/s (both P<0.001).Ticagrelor at a concentration ≥4 μmol/L almost completely inhibited platelet aggregation.The inhibition of ADP-induced platelet aggregation by ticagrelor was similar to the results under flow conditions and also in a concentration-dependent manner.Ticagrelor inhibited the expression of PAC-1 and CD62P. Conclusion We employed microfluidic chip to analyze platelet aggregation and flow cytometry to detect platelet activation,which can reveal the responses of different patients to ticagrelor.
Humans ; Ticagrelor/pharmacology* ; Platelet Aggregation Inhibitors/pharmacology* ; Flow Cytometry/methods* ; Microfluidics ; Platelet Aggregation

In vitro compartmentalization (IVC) links genotype and phenotype by compartmentalizing individual genes (including expression system) or cells into a micro-droplet reaction region. Combined with fluorescence-activated cell sorting (FACS), it can detect and separate single droplets in ultra-high throughput. IVC-FACS screening method has been widely used in protein engineering, enzyme directed evolution, etc. However, it is difficult to control the homogeneity of droplet size by mechanical dispersion method in previous studies, which seriously affects the quantitative detection of droplets and reduces the efficiency and accuracy of this screening method. With the rapid development of microfluidic chip manufacturing technology, the microfluidic chip-based methods for droplet generation are becoming more efficient and controllable. In this study, firstly, the water-in-oil (W/O) single-layer droplet generation chip was used to prepare single-layer monodisperse W1/O droplets at a high generation frequency, and then the W1/O droplets were reinjected into water-in-oil-in-water (W/O/W) double-layer droplet generation chip to prepare uniform W1/O/W2 double-layer emulsion droplets. By optimizing the flow rate and ratio of the oil and water phases, a single-layer micro-droplet can be generated with a diameter range from 15.4 to 23.2 μm and remain stable for several days under normal incubation. Then the single-layer droplets were reinjected into the double emulsion generation chip. By adjusting the flow rate of drop phase, oil phase and water phase, the double-layer emulsion droplets with a diameter range from 30 to 100 μm at a rate of 1 000 droplets/s could be obtained. Escherichia coli embedded in the double-layer emulsion droplets could be cultured and induced for protein expression. This study lays a foundation for the establishment of a high-throughput screening method based on the droplet and flow cytometry.
Emulsions ; Flow Cytometry ; High-Throughput Screening Assays ; Microfluidics ; methods

Liquid biopsy, the analysis of circulating biomarkers from peripheral blood, such as circulating tumor cells (CTCs) and circulating tumor DNA, and exosomes, offers a less invasive, new source of cancer-derived materials that may reflect the status of the disease better and thereby contribute to personalized treatment. Recent advances in microfluidics and molecular analysis technologies have resulted in greatly improved CTC enumeration and detection. In this article, we review commercially available technologies used to isolate CTCs from peripheral blood, including immunoaffinity and label-free, physical property-based isolation methods. Although enormous technological progress has been made, especially within the last decade, only a few CTC detection methods have been approved for routine clinical use. Here, we provide an overview of the current CTC isolation methods and examples of their potential application for early diagnosis, prognosis, treatment monitoring, and prediction of resistance to cancer therapy. Furthermore, the challenges that remain to be addressed before such tools are implemented for routine use in clinical settings are discussed.
Biomarkers ; Biopsy ; DNA ; Early Diagnosis ; Exosomes ; Humans ; Methods* ; Microfluidics ; Neoplastic Cells, Circulating* ; Prognosis ; Stomach Neoplasms

Red blood cell (RBC) dysfunction is often associated with a pathological intervention, and it has been proposed as a critical risk factor for certain lethal diseases. Examining the cell viability of RBCs under various physiological conditions is essential and of importance for precise diagnosis and drug discovery in the field of medicine and pharmacy. In this paper, we report a new analytical method that employs dielectrophoretic (DEP) force measurements in absolute units to assess the viability, and potentially the functionality of RBCs. We precisely quantify the frequency-dependent DEP forces of the RBCs by using a micro-electrode embedded chip combined with optical tweezers. DEP characteristics are known to be well-correlated with the viability of biological cells, and DEP forces are measured in both fresh and long-term stored RBCs to investigate the effect that the storage period has on the cell viability. Moreover, we investigate the DEP behavior of RBCs when exposed to oxidative stress and verify whether EDTA protects the RBCs from an oxidant. From the experiments, it is found that the fresh RBCs without oxidative stress display very high DEP forces over the entire frequency range, exhibiting two cutoff frequencies. However, both the RBCs stored for the long-term period and exposed to oxidative stress reveals that there exist no significant DEP forces over the frequency range. The results indicate that the DEP forces can serve as a useful parameter to verify whether the RBCs in certain blood are fresh and not exposed to oxidative stress. Therefore, it is believed that our system can be applied to a diagnostic system to monitor the cell viability of the RBCs or other types of cells.
Cell Survival ; Diagnosis ; Drug Discovery ; Edetic Acid ; Erythrocytes* ; Methods ; Microfluidics* ; Optical Tweezers* ; Oxidative Stress* ; Pharmacy ; Risk Factors

In tissue engineering, alginate has been an attractive material due to its biocompatibility and ability to form hydrogels, unless its uncontrollable degradation could be an undesirable feature. Here, we developed a simple and easy method to tune the degradation profile of the fibrous alginate scaffolds by the microfluidic wet spinning techniques, according with the use of isopropyl alcohol for dense packing of alginate chains in the microfiber production and the increase of crosslinking with Ca²⁺ ion. The degradation profiling was analyzed by mass losses, swelling ratios, and also observation of the morphologic changes. The results demonstrated that high packing density might be provided by self-aggregation of polymer chains through high dipole interactions between sheath and core fluids and that the increase of crosslinking rates could make degradation of alginate scaffold controllable. We suggest that the tunable degradation of the alginate fibrous scaffolds may expand its utilities for biomedical applications such as drug delivery, in vitro cell culture, wound healing, tissue engineering and regenerative medicine.
2-Propanol ; Cell Culture Techniques ; Hydrogel ; Hydrogels ; In Vitro Techniques ; Methods ; Microfluidics* ; Polymers ; Regenerative Medicine ; Tissue Engineering ; Wound Healing

Due to the low effectiveness of traditional assisted reproductive technology (ART), new technological possibilities are constantly explored. Lots of studies have demonstrated the potential of microfluidics to revolutionize the fundamental processes of in vitro fertilization (IVF). With the advantages of high efficiency, short time, harmless collection, real-time observation of separation, similar microenvironment, and automation, the application of microfluidics in sperm isolation and IVF has shown an evident superiority over the conventional approaches and provided a new platform for ART. This review highlights the application of various microfluidic techniques in sperm motility assessment and isolation, sperm chemotaxis assay, IVF, sperm concentration, and sperm separation and enrichment in recent years. It also briefly introduces the basic principles, structural design, and operation processes of the microfluidic platform, focusing on the advantages and disadvantages of each method and the potential of their clinical application. Obviously, there are still some challenges to the application of microfluidics in ART. However, it is believed that the development of this new technology would be toward a highly integrated application of several steps in one single device, known as IVF-lab-on-a-chip.
Fertilization in Vitro ; methods ; Humans ; In Vitro Techniques ; Male ; Microfluidics ; methods ; Reproductive Techniques, Assisted ; Sperm Motility ; Spermatozoa