Dielectrophoresis applications in biomedical field and future perspectives in biomedical technology.
TL;DR: A review of DEP applications in the biomedical field is presented in this article, where the authors highlight research work that shows significant approach related to DEP application in biomedical field reported between 2016 and 2020.
Abstract: Dielectrophoresis (DEP) is a technique to manipulate trajectories of polarisable particles in nonuniform electric fields by utilizing unique dielectric properties. The manipulation of a cell using DEP has been demonstrated in various modes, thereby indicating potential applications in the biomedical field. In this review, recent DEP applications in the biomedical field are discussed. This review is intended to highlight research work that shows significant approach related to DEP application in biomedical field reported between 2016 and 2020. First, single-shell model and multiple-shell model of cells are introduced. Current device structures and recently introduced electrode patterns for DEP applications are discussed. Second, the biomedical uses of DEP in liquid biopsies, stem cell-based therapies, and diagnosis of infectious diseases due to bacteria and viruses are presented. Finally, the challenges in DEP research are discussed, and the reported solutions are explained. DEP's potential research directions are mentioned.
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TL;DR: A detailed review of signal-based DEP methods can be found in this paper , where the applied signal parameters, including frequency, amplitude, phase, and shape for cell/particle separation and manipulation are discussed.
8 citations
TL;DR: In this paper , the authors focused on the recent advances in the lab-on-a-chip electrophoretic analysis of pathogenic bacteria and viruses in different complex matrices.
Abstract: Life‐threatening diseases, such as hepatitis B, pneumonia, tuberculosis, and COVID‐19, are widespread due to pathogenic bacteria and viruses. Therefore, the development of highly sensitive, rapid, portable, cost‐effective, and selective methods for the analysis of such microorganisms is a great challenge. Microchip electrophoresis (ME) has been widely used in recent years for the analysis of bacterial and viral pathogens in biological and environmental samples owing to its portability, simplicity, cost‐effectiveness, and rapid analysis. However, microbial enrichment and purification are critical steps for accurate and sensitive analysis of pathogenic bacteria and viruses in complex matrices. Therefore, we first discussed the advances in the sample preparation technologies associated with the accurate analysis of such microorganisms, especially the on‐chip microfluidic‐based sample preparations such as dielectrophoresis and microfluidic membrane filtration. Thereafter, we focused on the recent advances in the lab‐on‐a‐chip electrophoretic analysis of pathogenic bacteria and viruses in different complex matrices. As the microbial analysis is mainly based on the analysis of nucleic acid of the microorganism, the integration of nucleic acid‐based amplification techniques such as polymerase chain reaction (PCR), quantitative PCR, and multiplex PCR with ME will result in an accurate and sensitive analysis of microbial pathogens. Such analyses are very important for the point‐of‐care diagnosis of various infectious diseases.
3 citations
TL;DR: Three methods of electrical quantification of DEP responses are reviewed: electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV) and capacitance measurement for protein BSA DEP manipulation.
Abstract: Research relating to dielectrophoresis (DEP) has been progressing rapidly through time as it is a strong and controllable technique for manipulation, separation, preconcentration, and partitioning of protein. Extensive studies have been carried out on protein DEP, especially on Bovine Serum Albumin (BSA). However, these studies involve the usage of dye and fluorescent probes to observe DEP responses as the physical properties of protein albumin molecular structure are translucent. The use of dye and the fluorescent probe could later affect the protein’s physiology. In this article, we review three methods of electrical quantification of DEP responses: electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV) and capacitance measurement for protein BSA DEP manipulation. The correlation of these methods with DEP responses is further discussed. Based on the observations on capacitance measurement, it can be deduced that the electrical quantifying method is reliable for identifying DEP responses. Further, the possibility of manipulating the protein and electrically quantifying DEP responses while retaining the original physiology of the protein and without the usage of dye or fluorescent probe is discussed.
3 citations
TL;DR: In this article , the authors used DEP force (FDEP) to manipulate 3.2, 4.8, 10, and 15 μm polystyrene (PS) particles to predict the migration capability of human epidermal keratinocytes (HEKs).
Abstract: Diabetes affects approximately 170 million people worldwide, is expected to double by 2030, and is a severe problem. Electrical stimulation (ES) via dielectrophoresis (DEP) technique may be an effective alternative in enhancing healing rates in diabetic patients with open ulcers. This research used DEP force (FDEP) to manipulate 3.2, 4.8, 10, and 15 μm polystyrene (PS) particles to predict the migration capability of human epidermal keratinocytes (HEKs). A numerical modeling method, MyDEP, was used to predict the interpretation of Clausius–Mossotti factors of PS particles and HEKs. The finite element method computes the electric field intensity and particle trajectory based on DEP and drag forces in their respective medium. DEP experiments on numerous size PS particles and alive HEKs were carried out in a tapered aluminium microelectrode array using a non-uniform electric field. The distinct PS particles exhibit positive DEP (PDEP), crossover frequency (fXO), and negative DEP (NDEP), whereas the HEKs experience, only NDEP due to its high conductive medium in frequency ranges from 100 kHz to 1 MHz. Finally, the DIPP-MotionV analysis shows that particle mobility between speed and acceleration is statistically considerable. When an appropriate frequency is applied to HEKs in random locations, the FDEP aligns at the desired target position based on its dielectric properties, which accelerates wound healing in in-vivo conditions.
2 citations
TL;DR: In this article , the authors discuss the possible implementation of Fluid-Screen in the context of the Venus Life Finder (VLF) missions, emphasizing the unique science output of the FluidScreen instrument.
Abstract: Evidence of chemical disequilibria and other anomalous observations in the Venusian atmosphere motivate the search for life within the planet’s temperate clouds. To find signs of a Venusian aerial biosphere, a dedicated astrobiological space mission is required. Venus Life Finder (VLF) missions encompass unique mission concepts with specialized instruments to search for habitability indicators, biosignatures and even life itself. A key in the search for life is direct capture, concentration and visualization of particles of biological potential. Here, we present a short overview of Fluid-Screen (FS) technology, a recent advancement in the dielectrophoretic (DEP) microbial particle capture, concentration and separation. Fluid-Screen is capable of capturing and separating biochemically diverse particles, including multicellular molds, eukaryotic cells, different species of bacteria and even viruses, based on particle dielectric properties. In this short communication, we discuss the possible implementation of Fluid-Screen in the context of the Venus Life Finder (VLF) missions, emphasizing the unique science output of the Fluid-Screen instrument. FS can be coupled with other highly sophisticated instruments such as an autofluorescence microscope or a laser desorption mass spectrometer (LDMS). We discuss possible configurations of Fluid-Screen that upon modification and testing, could be adapted for Venus. We discuss the unique science output of the Fluid-Screen technology that can capture biological particles in their native state and hold them in the focal plane of the microscope for the direct imaging of the captured material. We discuss the challenges for the proposed method posed by the concentrated sulfuric acid environment of Venus’ clouds. While Venus’ clouds are a particularly challenging environment, other bodies of the solar system, e.g., with liquid water present, might be especially suitable for Fluid-Screen application.
2 citations
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TL;DR: The CTC-chip successfully identified CTCs in the peripheral blood of patients with metastatic lung, prostate, pancreatic, breast and colon cancer in 115 of 116 samples, with a range of 5–1,281CTCs per ml and approximately 50% purity.
Abstract: Viable tumour-derived epithelial cells (circulating tumour cells or CTCs) have been identified in peripheral blood from cancer patients and are probably the origin of intractable metastatic disease. Although extremely rare, CTCs represent a potential alternative to invasive biopsies as a source of tumour tissue for the detection, characterization and monitoring of non-haematologic cancers. The ability to identify, isolate, propagate and molecularly characterize CTC subpopulations could further the discovery of cancer stem cell biomarkers and expand the understanding of the biology of metastasis. Current strategies for isolating CTCs are limited to complex analytic approaches that generate very low yield and purity. Here we describe the development of a unique microfluidic platform (the 'CTC-chip') capable of efficient and selective separation of viable CTCs from peripheral whole blood samples, mediated by the interaction of target CTCs with antibody (EpCAM)-coated microposts under precisely controlled laminar flow conditions, and without requisite pre-labelling or processing of samples. The CTC-chip successfully identified CTCs in the peripheral blood of patients with metastatic lung, prostate, pancreatic, breast and colon cancer in 115 of 116 (99%) samples, with a range of 5-1,281 CTCs per ml and approximately 50% purity. In addition, CTCs were isolated in 7/7 patients with early-stage prostate cancer. Given the high sensitivity and specificity of the CTC-chip, we tested its potential utility in monitoring response to anti-cancer therapy. In a small cohort of patients with metastatic cancer undergoing systemic treatment, temporal changes in CTC numbers correlated reasonably well with the clinical course of disease as measured by standard radiographic methods. Thus, the CTC-chip provides a new and effective tool for accurate identification and measurement of CTCs in patients with cancer. It has broad implications in advancing both cancer biology research and clinical cancer management, including the detection, diagnosis and monitoring of cancer.
3,450 citations
TL;DR: This review comprehensively covers the epidemiology, pathophysiology, clinical manifestations, and management of S. aureus as a leading cause of bacteremia and infective endocarditis as well as osteoarticular, skin and soft tissue, pleuropulmonary, and device-related infections.
Abstract: Staphylococcus aureus is a major human pathogen that causes a wide range of clinical infections. It is a leading cause of bacteremia and infective endocarditis as well as osteoarticular, skin and soft tissue, pleuropulmonary, and device-related infections. This review comprehensively covers the epidemiology, pathophysiology, clinical manifestations, and management of each of these clinical entities. The past 2 decades have witnessed two clear shifts in the epidemiology of S. aureus infections: first, a growing number of health care-associated infections, particularly seen in infective endocarditis and prosthetic device infections, and second, an epidemic of community-associated skin and soft tissue infections driven by strains with certain virulence factors and resistance to β-lactam antibiotics. In reviewing the literature to support management strategies for these clinical manifestations, we also highlight the paucity of high-quality evidence for many key clinical questions.
3,054 citations
TL;DR: The serial respiratory viral load of SARS-CoV-2 in posterior oropharyngeal saliva samples from patients with COVID-19, and serum antibody responses from patients infected with severe acute respiratory syndrome coronavirus 2 are ascertained.
Abstract: Summary Background Coronavirus disease 2019 (COVID-19) causes severe community and nosocomial outbreaks. Comprehensive data for serial respiratory viral load and serum antibody responses from patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not yet available. Nasopharyngeal and throat swabs are usually obtained for serial viral load monitoring of respiratory infections but gathering these specimens can cause discomfort for patients and put health-care workers at risk. We aimed to ascertain the serial respiratory viral load of SARS-CoV-2 in posterior oropharyngeal (deep throat) saliva samples from patients with COVID-19, and serum antibody responses. Methods We did a cohort study at two hospitals in Hong Kong. We included patients with laboratory-confirmed COVID-19. We obtained samples of blood, urine, posterior oropharyngeal saliva, and rectal swabs. Serial viral load was ascertained by reverse transcriptase quantitative PCR (RT-qPCR). Antibody levels against the SARS-CoV-2 internal nucleoprotein (NP) and surface spike protein receptor binding domain (RBD) were measured using EIA. Whole-genome sequencing was done to identify possible mutations arising during infection. Findings Between Jan 22, 2020, and Feb 12, 2020, 30 patients were screened for inclusion, of whom 23 were included (median age 62 years [range 37–75]). The median viral load in posterior oropharyngeal saliva or other respiratory specimens at presentation was 5·2 log10 copies per mL (IQR 4·1–7·0). Salivary viral load was highest during the first week after symptom onset and subsequently declined with time (slope −0·15, 95% CI −0·19 to −0·11; R2=0·71). In one patient, viral RNA was detected 25 days after symptom onset. Older age was correlated with higher viral load (Spearman's ρ=0·48, 95% CI 0·074–0·75; p=0·020). For 16 patients with serum samples available 14 days or longer after symptom onset, rates of seropositivity were 94% for anti-NP IgG (n=15), 88% for anti-NP IgM (n=14), 100% for anti-RBD IgG (n=16), and 94% for anti-RBD IgM (n=15). Anti-SARS-CoV-2-NP or anti-SARS-CoV-2-RBD IgG levels correlated with virus neutralisation titre (R2>0·9). No genome mutations were detected on serial samples. Interpretation Posterior oropharyngeal saliva samples are a non-invasive specimen more acceptable to patients and health-care workers. Unlike severe acute respiratory syndrome, patients with COVID-19 had the highest viral load near presentation, which could account for the fast-spreading nature of this epidemic. This finding emphasises the importance of stringent infection control and early use of potent antiviral agents, alone or in combination, for high-risk individuals. Serological assay can complement RT-qPCR for diagnosis. Funding Richard and Carol Yu, May Tam Mak Mei Yin, The Shaw Foundation Hong Kong, Michael Tong, Marina Lee, Government Consultancy Service, and Sanming Project of Medicine.
2,778 citations
TL;DR: This review of the essential features of theoretical models of electroporation focuses on transient aqueous pore models, which can account for key features of mechanical instability and dramatic reversible electrical behavior of certain planar membranes and of cell membranes, and some features of molecular transport.
1,539 citations
TL;DR: It is demonstrated that lymphatics can be established in solid tumors and implicates VEGF family members in determining the route of metastatic spread and could be blocked with an antibody specific for V EGF-D.
Abstract: Metastasis to local lymph nodes via the lymphatic vessels is a common step in the spread of solid tumors. To investigate the molecular mechanisms underlying the spread of cancer by the lymphatics, we examined the ability of vascular endothelial growth factor (VEGF)-D, a ligand for the lymphatic growth factor receptor VEGFR-3/Flt-4, to induce formation of lymphatics in a mouse tumor model. Staining with markers specific for lymphatic endothelium demonstrated that VEGF-D induced the formation of lymphatics within tumors. Moreover, expression of VEGF-D in tumor cells led to spread of the tumor to lymph nodes, whereas expression of VEGF, an angiogenic growth factor which activates VEGFR-2 but not VEGFR-3, did not. VEGF-D also promoted tumor angiogenesis and growth. Lymphatic spread induced by VEGF-D could be blocked with an antibody specific for VEGF-D. This study demonstrates that lymphatics can be established in solid tumors and implicates VEGF family members in determining the route of metastatic spread.
1,203 citations