1.Inertial label-free sorting and chemotaxis of polymorphonuclear neutrophil in sepsis patients based on microfluidic technology.
Chaoru GAO ; Xiao YANG ; Lijuan LIU ; Yue WANG ; Ling ZHU ; Jinhua ZHOU ; Yong LIU ; Ke YANG
Journal of Biomedical Engineering 2023;40(6):1217-1226
Reduced chemotactic migration of polymorphonuclear neutrophil (PMN) in sepsis patients leads to decreased bacterial clearance and accelerates the progression of sepsis disease. Quantification of PMN chemotaxis in sepsis patients can help characterize the immune health of sepsis patients. Microfluidic microarrays have been widely used for cell chemotaxis analysis because of the advantages of low reagent consumption, near-physiological environment, and visualization of the migration process. Currently, the study of PMN chemotaxis using microfluidic chips is mainly limited by the cumbersome cell separation operation and low throughput of microfluidic chips. In this paper, we first designed an inertial cell sorting chip to achieve label-free separation of the two major cell types by using the basic principle that leukocytes (mainly granulocytes, lymphocytes and monocytes) and erythrocytes move to different positions of the spiral microchannel when they move in the spiral microchannel under different strength of inertial force and Dean's resistance. Subsequently, in this paper, we designed a multi-channel cell migration chip and constructed a microfluidic PMN inertial label-free sorting and chemotaxis analysis platform. The inertial cell sorting chip separates leukocyte populations and then injects them into the multi-channel cell migration chip, which can complete the chemotaxis test of PMN to chemotactic peptide (fMLP) within 15 min. The remaining cells, such as monocytes with slow motility and lymphocytes that require pre-activation with proliferative culture, do not undergo significant chemotactic migration. The test results of sepsis patients ( n=6) and healthy volunteers ( n=3) recruited in this study showed that the chemotaxis index (CI) and migration velocity ( v) of PMN from sepsis patients were significantly weaker than those from healthy volunteers. In conclusion, the microfluidic PMN inertial label-free sorting and chemotaxis analysis platform constructed in this paper can be used as a new tool for cell label-free sorting and migration studies.
Humans
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Chemotaxis
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Neutrophils/metabolism*
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Microfluidics
;
Cell Movement
;
Sepsis/metabolism*
2.Cell-loaded hydrogel microspheres based on droplet microfluidics: a review.
Caiyun ZHANG ; Yi ZENG ; Na XU ; Zhiling ZHANG
Chinese Journal of Biotechnology 2023;39(1):74-85
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*
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Microfluidics/methods*
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Microspheres
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Regenerative Medicine
;
Tissue Engineering/methods*
3.Detection of IgG protein in human urine based on vertical flow paper microfluidic chip.
Xinru LI ; Xinyi WANG ; Ziyu WEI ; Penghui ZHANG ; Jingwen XU ; Lang XU ; Feifan ZHENG ; Zhenwei YANG ; Yuanyuan CHEN ; Xianbo QIU ; Lulu ZHANG
Chinese Journal of Biotechnology 2023;39(1):337-346
The kidney is the body's most important organ and the protein components in urine could be detected for diagnosing certain diseases. The amount of IgG protein in urine could be used to determine the degree of kidney function damage. IgG protein in human urine was detected by vertical flow paper-based microfluidic chip, double-antibody sandwich immunoreaction, and cell phone image processing. The results showed that using an IgG antibody concentration of 500 μg/mL and a gold standard antibody concentration of 100 μg/mL, the image signal showed a good linear relationship in the range of IgG concentration of 0.2-3.2 μg/mL, with R2=0.973 3 achieved. A complete set of detection devices were designed and the detection method showed good non-specificity.
Humans
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Microfluidics
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Immunoglobulin G
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Kidney
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Microfluidic Analytical Techniques
4.Mechanism of blood-activating and mass-dissipating Chinese patent medicine against hyperplasia of mammary glands and use with other medicine: a review.
Qi-Rui FAN ; Mei CHEN ; Xiao-Yi DONG ; Rui TAO ; Jing-Rui WANG ; Shun-Li XIA ; Tao HAN
China Journal of Chinese Materia Medica 2023;48(2):292-299
Caused by endocrine disorder, hyperplasia of mammary glands(HMG) tends to occur in the young with increasing incidence, putting patients at the risk of cancer and threatening the health of women. Therefore, the prevention and treatment of HMG is attracting more and more attention. Amid the modernization of traditional Chinese medicine(TCM), many scholars have found that Chinese patent medicine has unique advantages and huge potential in treatment of endocrine disorder. Particularly, Chinese patent medicine with the function of blood-activating and mass-dissipating, such as Xiaojin Pills and Xiaozheng Pills, has been commonly used in clinical treatment of HMG, which features multiple targets, obvious efficacy, small side effect, and ease of taking and carrying around. Clinical studies have found that the combination of Chinese patent medicine with other medicine can not only improve the efficacy and relieve symptoms such as hyperplasia and pain but also reduce the toxic and side effects of western medicine. Therefore, based on precious pharmacological research and clinical research, this study reviewed the mechanisms of blood-activating mass-dissipating Chinese patent medicine alone and in combination with other medicine, such as regulating levels of in vivo hormones and receptors, promoting apoptosis, inhibiting angiogenesis, improving hemorheology indexes, enhancing immunity, and boosting antioxidant ability. In addition, limitations and problems were summarized. Thereby, this study is expected to lay a theoretical basis for the further study and clinical application of blood-activating mass-dissipating Chinese patent medicine alone or in combination with other medicine against HMG.
Humans
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Female
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Hyperplasia/drug therapy*
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Nonprescription Drugs
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Mammary Glands, Human/pathology*
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Medicine, Chinese Traditional
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Hemorheology
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Drugs, Chinese Herbal/therapeutic use*
5.Microfluidic Chip and Flow Cytometry for Examination of the Antiplatelet Effect of Ticagrelor.
Xiao-Jing HUANG ; Tian-Cong ZHANG ; Xue-Mei GAO ; Cui HE ; Xuan-Rong HUAN ; Yuan LI
Acta Academiae Medicinae Sinicae 2023;45(2):257-263
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
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Ticagrelor/pharmacology*
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Platelet Aggregation Inhibitors/pharmacology*
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Flow Cytometry/methods*
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Microfluidics
;
Platelet Aggregation
6.Study on Platelet Adhesion and Aggregation Induced by Gradient Shear Stress Using Microfluidic Chip Technology.
Hai-Dong MA ; Cui HE ; Su-Rong DENG ; Ting-Ting ZHANG ; Yuan LI ; Tian-Cong ZHANG
Journal of Experimental Hematology 2023;31(2):495-502
OBJECTIVE:
To study the effect of gradient shear stress on platelet aggregation by microfluidic chip Technology.
METHODS:
Microfluidic chip was used to simulate 80% fixed stenotic microchannel, and the hydrodynamic behavior of the stenotic microchannel model was analyzed by the finite element analysis module of sollidwork software. Microfluidic chip was used to analyze the adhesion and aggregation behavior of platelets in patients with different diseases, and flow cytometry was used to detect expression of the platelet activation marker CD62p. Aspirin, Tirofiban and protocatechuic acid were used to treat the blood, and the adhesion and aggregation of platelets were observed by fluorescence microscope.
RESULTS:
The gradient fluid shear rate produced by the stenosis model of microfluidic chip could induce platelet aggregation, and the degree of platelet adhesion and aggregation increased with the increase of shear rate within a certain range of shear rate. The effect of platelet aggregation in patients with arterial thrombotic diseases were significantly higher than normal group (P<0.05), and the effect of platelet aggregation in patients with myelodysplastic disease was lower than normal group (P<0.05).
CONCLUSION
The microfluidic chip analysis technology can accurately analyze and evaluate the platelet adhesion and aggregation effects of various thrombotic diseases unde the environment of the shear rate, and is helpful for auxiliary diagnosis of clinical thrombotic diseases.
Humans
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Microfluidics
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Platelet Adhesiveness
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Platelet Aggregation
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Blood Platelets/metabolism*
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Platelet Aggregation Inhibitors/pharmacology*
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Platelet Activation/physiology*
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Thrombosis
7.Application of microfluidic assays for cardiovascular disease markers in early warning and rapid diagnosis.
Tai Ju CHEN ; Rui Ning LIU ; Hong ZHANG ; Hua Ming MOU ; Yang LUO
Chinese Journal of Preventive Medicine 2023;57(7):1115-1123
Cardiovascular disease is a major threat to human health and has become the leading cause of death worldwide; therefore, early diagnosis and treatment are of great value. Due to its miniaturization, integration, and ease of operation, microfluidic technology enables the rapid, multi-target detection of cardiovascular disease markers and significantly facilitates the early and rapid diagnosis of cardiovascular disease. This article reviews the research progress of microfluidics in cardiovascular disease detection, analyzes its advantages and weaknesses in the rapid detection of protein, lipid, and nucleic acid biomarkers, hopes to provide a reference to promote the quick detection technology of cardiovascular disease, and thus proposes new considerations for the early management of cardiovascular disease.
Humans
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Microfluidics
;
Cardiovascular Diseases/diagnosis*
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Biomarkers
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Early Diagnosis
8.Research advances on the techniques for diagnosing burn wound depth.
Yi Jia LIU ; Peng WU ; Gang AN ; Qiu FANG ; Jia ZHENG ; Yi Bing WANG
Chinese Journal of Burns 2022;38(5):481-485
The accurate diagnosis of burn wound depth is particularly important for evaluating the disease prognosis of burn patients. In the past, the diagnosis of burn wound depth often relied on the subjective judgment of doctors. With the continuous development of diagnostic technology, the methods for judging the depth of burn wound have also been updated. This paper mainly summarizes the research progress in the applications of indocyanine green angiography, laser Doppler imaging, laser speckle contrast imaging, and artificial intelligence in the diagnosis of burn wound depth, and compares the advantages and disadvantages of these techniques, so as to provide ideas for accurate diagnosis of burn wound depth.
Angiography
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Artificial Intelligence
;
Burns/diagnosis*
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Humans
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Laser-Doppler Flowmetry/methods*
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Skin
;
Wound Healing
9.Visualization analysis of microfluidics research status.
Wei WEI ; Ruijun WU ; Xiaodong SANG ; Tianyu LIANG ; Zhifei LI ; Zhi LI ; Yang YANG ; Yue SU
Journal of Biomedical Engineering 2022;39(3):551-560
Microfluidics is the science and technology to manipulate small amounts of fluids in micro/nano-scale space. Multiple modules could be integrated into microfluidic device, and due to its advantages of microminiaturization and controllability, microfluidics has drawn extensive attention since its birth. In this paper, the literature data related to microfluidics research from January 1, 2006 to December 31, 2021 were obtained from Web of Science Core Collection database. CiteSpace 5.8.R3 software was used for bibliometrics analysis, so as to explore the research progress and development trends of microfluidics research at home and abroad. Based on the analysis of 50 129 articles, it could be seen that microfluidics was a hot topic of global concern, and the United States had a certain degree of authority in this field. Massachusetts Institute of Technology and Harvard University not only had a high number of publications, but also had strong influence and extensive cooperation network. Combined with ultrasonic, surface modification and sensor technology, researchers constructed paper-based microfluidic, droplet microfluidic and digital microfluidic platforms, which were applied in the field of immediate diagnosis, nucleic acid and circulating tumor cell analysis of in vitro diagnosis and organ-on-a-chip. China was one of the countries with a high level of research in the field of microfluidics, while the industrialization of high-end products needed to be improved. As people's demand for disease risk prediction and health management increased, promoting microfluidic technological innovation and achievement transformation is of great significance to safeguard people's life and health.
China
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Humans
;
Microfluidic Analytical Techniques
;
Microfluidics
;
Oligonucleotide Array Sequence Analysis
10.Design, simulation and application of multichannel microfluidic chip for cell migration.
Huilai LI ; Xiao YANG ; Xiaosong WU ; Zhigang LI ; Chenggang HONG ; Yong LIU ; Ling ZHU ; Ke YANG
Journal of Biomedical Engineering 2022;39(1):128-138
Cell migration is defined as the directional movement of cells toward a specific chemical concentration gradient, which plays a crucial role in embryo development, wound healing and tumor metastasis. However, current research methods showed low flux and are only suitable for single-factor assessment, and it was difficult to comprehensively consider the effects of other parameters such as different concentration gradients on cell migration behavior. In this paper, a four-channel microfluidic chip was designed. Its characteristics were as follows: it relied on laminar flow and diffusion mechanisms to establish and maintain a concentration gradient; it was suitable for observation of cell migration in different concentration gradient environment under a single microscope field; four cell isolation zones (20 μm width) were integrated into the microfluidic device to calibrate the initial cell position, which ensured the accuracy of the experimental results. In particular, we used COMSOL Multiphysics software to simulate the structure of the chip, which demonstrated the necessity of designing S-shaped microchannel and horizontal pressure balance channel to maintain concentration gradient. Finally, neutrophils were incubated with advanced glycation end products (AGEs, 0, 0.2, 0.5, 1.0 μmol·L -1), which were closely related to diabetes mellitus and its complications. The migration behavior of incubated neutrophils was studied in the 100 nmol·L -1 of chemokine (N-formylmethionyl-leucyl-phenyl-alanine) concentration gradient. The results prove the reliability and practicability of the microfluidic chip.
Cell Movement
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Chemotaxis
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Equipment Design
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Lab-On-A-Chip Devices
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Microfluidic Analytical Techniques
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Microfluidics
;
Neutrophils
;
Reproducibility of Results

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