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1.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 2249-2252, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018455

RESUMO

We report on a unique microfluidic device that can enrich nanoparticles in a continuous flow by railing them along activated tracks (electrodes). This was achieved based on dielectrophoretic force and electrohydrodynamic drag (electrothermal rolls and AC electroosmosis) in both low and high conductive media. The results have implication for the isolation of high quality and pure nanoparticles such as exosomes from biofluids for applications in cancer diagnosis and prognosis.


Assuntos
Técnicas Analíticas Microfluídicas , Nanopartículas , Condutividade Elétrica , Eletro-Osmose , Dispositivos Lab-On-A-Chip
3.
Nat Commun ; 11(1): 4489, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895384

RESUMO

We report a covalent chemistry-based hepatocellular carcinoma (HCC)-specific extracellular vesicle (EV) purification system for early detection of HCC by performing digital scoring on the purified EVs. Earlier detection of HCC creates more opportunities for curative therapeutic interventions. EVs are present in circulation at relatively early stages of disease, providing potential opportunities for HCC early detection. We develop an HCC EV purification system (i.e., EV Click Chips) by synergistically integrating covalent chemistry-mediated EV capture/release, multimarker antibody cocktails, nanostructured substrates, and microfluidic chaotic mixers. We then explore the translational potential of EV Click Chips using 158 plasma samples of HCC patients and control cohorts. The purified HCC EVs are subjected to reverse-transcription droplet digital PCR for quantification of 10 HCC-specific mRNA markers and computation of digital scoring. The HCC EV-derived molecular signatures exhibit great potential for noninvasive early detection of HCC from at-risk cirrhotic patients with an area under receiver operator characteristic curve of 0.93 (95% CI, 0.86 to 1.00; sensitivity = 94.4%, specificity = 88.5%).


Assuntos
Biomarcadores Tumorais/isolamento & purificação , Carcinoma Hepatocelular/diagnóstico , Detecção Precoce de Câncer/métodos , Vesículas Extracelulares/genética , Neoplasias Hepáticas/diagnóstico , Idoso , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Química Click/instrumentação , Química Click/métodos , Química Computacional , Simulação por Computador , Diagnóstico Diferencial , Dimetilpolisiloxanos/química , Progressão da Doença , Detecção Precoce de Câncer/instrumentação , Feminino , Células Hep G2 , Humanos , Dispositivos Lab-On-A-Chip , Biópsia Líquida/instrumentação , Biópsia Líquida/métodos , Cirrose Hepática/sangue , Cirrose Hepática/patologia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Técnicas Analíticas Microfluídicas/instrumentação , Técnicas Analíticas Microfluídicas/métodos , Pessoa de Meia-Idade , Nanoestruturas/química , Nanofios/química , Estadiamento de Neoplasias , RNA Mensageiro/genética , RNA Mensageiro/isolamento & purificação , Curva ROC , Reação em Cadeia da Polimerase Via Transcriptase Reversa/instrumentação , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos
4.
Nat Commun ; 11(1): 4405, 2020 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-32879320

RESUMO

Active biofluid management is central to the realization of wearable bioanalytical platforms that are poised to autonomously provide frequent, real-time, and accurate measures of biomarkers in epidermally-retrievable biofluids (e.g., sweat). Accordingly, here, a programmable epidermal microfluidic valving system is devised, which is capable of biofluid sampling, routing, and compartmentalization for biomarker analysis. At its core, the system is a network of individually-addressable microheater-controlled thermo-responsive hydrogel valves, augmented with a pressure regulation mechanism to accommodate pressure built-up, when interfacing sweat glands. The active biofluid control achieved by this system is harnessed to create unprecedented wearable bioanalytical capabilities at both the sensor level (decoupling the confounding influence of flow rate variability on sensor response) and the system level (facilitating context-based sensor selection/protection). Through integration with a wireless flexible printed circuit board and seamless bilateral communication with consumer electronics (e.g., smartwatch), contextually-relevant (scheduled/on-demand) on-body biomarker data acquisition/display was achieved.


Assuntos
Biomarcadores/análise , Técnicas Analíticas Microfluídicas/métodos , Microfluídica , Técnicas Biossensoriais , Epiderme/química , Humanos , Suor/química , Dispositivos Eletrônicos Vestíveis
5.
Nat Commun ; 11(1): 4851, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32978386

RESUMO

Cell factories converting bio-based precursors to chemicals present an attractive avenue to a sustainable economy, yet screening of genetically diverse strain libraries to identify the best-performing whole-cell biocatalysts is a low-throughput endeavor. For this reason, transcriptional biosensors attract attention as they allow the screening of vast libraries when used in combination with fluorescence-activated cell sorting (FACS). However, broad ligand specificity of transcriptional regulators (TRs) often prohibits the development of such ultra-high-throughput screens. Here, we solve the structure of the TR LysG of Corynebacterium glutamicum, which detects all three basic amino acids. Based on this information, we follow a semi-rational engineering approach using a FACS-based screening/counterscreening strategy to generate an L-lysine insensitive LysG-based biosensor. This biosensor can be used to isolate L-histidine-producing strains by FACS, showing that TR engineering towards a more focused ligand spectrum can expand the scope of application of such metabolite sensors.


Assuntos
Sistemas de Transporte de Aminoácidos Básicos/química , Proteínas de Bactérias/química , Técnicas Biossensoriais/métodos , Ligantes , Engenharia Metabólica/métodos , Sistemas de Transporte de Aminoácidos Básicos/metabolismo , Proteínas de Bactérias/metabolismo , Corynebacterium glutamicum/metabolismo , Cristalografia , Citometria de Fluxo/métodos , Ensaios de Triagem em Larga Escala/métodos , Lisina/metabolismo , Técnicas Analíticas Microfluídicas , Modelos Moleculares , Conformação Proteica , Domínios Proteicos , Termodinâmica
6.
Biosens Bioelectron ; 169: 112572, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32916610

RESUMO

Convalescent serum with a high abundance of neutralization IgG is a promising therapeutic agent for rescuing COVID-19 patients in the critical stage. Knowing the concentration of SARS-CoV-2 S1-specific IgG is crucial in selecting appropriate convalescent serum donors. Here, we present a portable microfluidic ELISA technology for rapid (15 min), quantitative, and sensitive detection of anti-SARS-CoV-2 S1 IgG in human serum with only 8 µL sample volume. We first identified a humanized monoclonal IgG that has a high binding affinity and a relatively high specificity towards SARS-CoV-2 S1 protein, which can subsequently serve as the calibration standard of anti-SARS-CoV-2 S1 IgG in serological analyses. We then measured the abundance of anti-SARS-CoV-2 S1 IgG in 16 convalescent COVID-19 patients. Due to the availability of the calibration standard and the large dynamic range of our assay, we were able to identify "qualified donors" for convalescent serum therapy with only one fixed dilution factor (200 ×). Finally, we demonstrated that our technology can sensitively detect SARS-CoV-2 antigens (S1 and N proteins) with pg/mL level sensitivities in 40 min. Overall, our technology can greatly facilitate rapid, sensitive, and quantitative analysis of COVID-19 related markers for therapeutic, diagnostic, epidemiologic, and prognostic purposes.


Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Infecções por Coronavirus/virologia , Ensaio de Imunoadsorção Enzimática/instrumentação , Imunoglobulina G/sangue , Técnicas Analíticas Microfluídicas/instrumentação , Pneumonia Viral/virologia , Adolescente , Adulto , Anticorpos Antivirais/imunologia , Antígenos Virais/sangue , Antígenos Virais/imunologia , Técnicas Biossensoriais/economia , Técnicas Biossensoriais/instrumentação , Infecções por Coronavirus/terapia , Ensaio de Imunoadsorção Enzimática/economia , Desenho de Equipamento , Humanos , Imunização Passiva , Imunoglobulina G/imunologia , Limite de Detecção , Medições Luminescentes/economia , Medições Luminescentes/instrumentação , Técnicas Analíticas Microfluídicas/economia , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/terapia , Fatores de Tempo , Adulto Jovem
7.
Sheng Wu Gong Cheng Xue Bao ; 36(7): 1283-1292, 2020 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-32748586

RESUMO

Point-of-care testing (POCT) is a test method performed on the sampling site or patient bedside. 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, simple operation, rapid detection, portable equipment, and unrestricted application conditions. 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. The classification and characteristic of the paper are summarized in this review. Paper-based microfluidic sample pretreatment methods, the flow control in the process of reaction and the signal detecting and analyzing methods for the testing results are introduced. The research progress of various kinds of microfluidic paper-based analytical devices (µPADs) toward POCT in recent years is reviewed. Finally, remaining problems and the future prospects in POCT application of paper-based microfluidics are discussed.


Assuntos
Testes Diagnósticos de Rotina , Técnicas Analíticas Microfluídicas , Papel , Testes Imediatos , Testes Diagnósticos de Rotina/métodos , Humanos , Técnicas Analíticas Microfluídicas/instrumentação
8.
Nat Commun ; 11(1): 4244, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32843650

RESUMO

Acoustical tweezers open major prospects in microbiology for cells and microorganisms contactless manipulation, organization and mechanical properties testing since they are biocompatible, label-free and have the potential to exert forces several orders of magnitude larger than their optical counterpart at equivalent power. Yet, these perspectives have so far been hindered by the absence of spatial selectivity of existing acoustical tweezers - i.e., the ability to select and move objects individually - and/or their limited resolution restricting their use to large particle manipulation only and/or finally the limited forces that they could apply. Here, we report precise selective manipulation and positioning of individual human cells in a standard microscopy environment with trapping forces up to ~200 pN without altering their viability. These results are obtained with miniaturized acoustical tweezers combining holography with active materials to synthesize specific wavefields called focused acoustical vortices designed to produce stiff localized traps with reduced acoustic power.


Assuntos
Acústica , Técnicas Citológicas/instrumentação , Técnicas Analíticas Microfluídicas/instrumentação , Linhagem Celular Tumoral , Sobrevivência Celular , Desenho de Equipamento , Holografia , Humanos , Microscopia
9.
J Chromatogr A ; 1626: 461262, 2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32797810

RESUMO

In this paper, a semi-analytical investigation was performed to study the effect of the geometrical parameters of insulator-based dielectrophoresis (iDEP) systems for cell free DNA (cfDNA) trapping. For this purpose, first electrical potential and fluid flow fields were calculated by solving the governing equations including Poisson and Navier-stokes equations with appropriate boundary conditions (BCs) and then a Lagrangian approach was utilized to analyze the motion of cfDNA under the most important forces affected on it including Brownian, Drag, electrophoresis and dielectrophoresis (DEP) forces. The effect of the different parameters such as the electrical conductivity of the medium, shape and geometrical parameters of the insulators on the dielectrophoretic behavior of cfDNA was studied and the optimal value of these parameters was presented. Finally, in order to predict the minimum voltage required for cfDNA trapping, artificial neural network (ANN) was utilized and a relation between input and output parameters was introduced.


Assuntos
Ácidos Nucleicos Livres/química , Eletroforese/métodos , Nanopartículas/química , Condutividade Elétrica , Técnicas Analíticas Microfluídicas , Redes Neurais de Computação
11.
Anal Chem ; 92(14): 9454-9458, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32615038

RESUMO

The outbreak of SARS-CoV-2 is posing serious global public health problems. Facing the emergence of this pandemic, we established a portable microfluidic immunoassay system for easy-to-use, sensitive, rapid (<15 min), multiple, and on-site detection of IgG/IgM/Antigen of SARS-CoV-2 simultaneously. This integrated method was successfully applied for detecting SARS-CoV-2 IgM and IgG antibodies in clinical human serum as well as SARS-CoV-2 antigen in pharyngeal swabs from 26 patients with COVID-19 infection and 28 uninfected people. The assay demonstrated high sensitivity and specificity, which is promising for the diagnosis and monitoring as well as control of SARS-CoV-2 worldwide.


Assuntos
Anticorpos Antivirais/análise , Betacoronavirus/imunologia , Infecções por Coronavirus/diagnóstico , Imunoensaio/métodos , Imunoglobulina G/análise , Imunoglobulina M/análise , Técnicas Analíticas Microfluídicas/métodos , Pneumonia Viral/diagnóstico , Técnicas de Laboratório Clínico/métodos , Ensaio de Imunoadsorção Enzimática , Humanos , Pandemias , Faringe/química , Faringe/imunologia , Sensibilidade e Especificidade
12.
Proc Natl Acad Sci U S A ; 117(27): 15659-15665, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32581119

RESUMO

Cell size is believed to influence cell growth and metabolism. Consistently, several studies have revealed that large cells have lower mass accumulation rates per unit mass (i.e., growth efficiency) than intermediate-sized cells in the same population. Size-dependent growth is commonly attributed to transport limitations, such as increased diffusion timescales and decreased surface-to-volume ratio. However, separating cell size- and cell cycle-dependent growth is challenging. To address this, we monitored growth efficiency of pseudodiploid mouse lymphocytic leukemia cells during normal proliferation and polyploidization. This was enabled by the development of large-channel suspended microchannel resonators that allow us to monitor buoyant mass of single cells ranging from 40 pg (small pseudodiploid cell) to over 4,000 pg, with a resolution ranging from ∼1% to ∼0.05%. We find that cell growth efficiency increases, plateaus, and then decreases as cell cycle proceeds. This growth behavior repeats with every endomitotic cycle as cells grow into polyploidy. Overall, growth efficiency changes 33% throughout the cell cycle. In contrast, increasing cell mass by over 100-fold during polyploidization did not change growth efficiency, indicating exponential growth. Consistently, growth efficiency remained constant when cell cycle was arrested in G2 Thus, cell cycle is a primary determinant of growth efficiency. As growth remains exponential over large size scales, our work finds no evidence for transport limitations that would decrease growth efficiency.


Assuntos
Técnicas Biossensoriais , Crescimento Celular , Proliferação de Células/genética , Leucemia Linfoide/genética , Animais , Ciclo Celular/genética , Divisão Celular/genética , Linhagem Celular Tumoral , Humanos , Leucemia Linfoide/patologia , Camundongos , Técnicas Analíticas Microfluídicas , Poliploidia
13.
Proc Natl Acad Sci U S A ; 117(26): 14798-14804, 2020 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-32554496

RESUMO

Proper circulation of white blood cells (WBCs) in the pulmonary vascular bed is crucial for an effective immune response. In this branched vascular network, WBCs have to strongly deform to pass through the narrowest capillaries and bifurcations. Although it is known that this process depends on the cell mechanical properties, it is still poorly understood due to the lack of a comprehensive model of cell mechanics and of physiologically relevant experiments. Here, using an in-house microfluidic device mimicking the pulmonary capillary bed, we show that the dynamics of THP1 monocytes evolves along successive capillary-like channels, from a nonstationary slow motion with hops to a fast and smooth efficient one. We used actin cytoskeleton drugs to modify the traffic dynamics. This led us to propose a simple mechanical model that shows that a very finely tuned cortical tension combined with a high cell viscosity governs the fast transit through the network while preserving cell integrity. We finally highlight that the cortical tension controls the steady-state cell velocity via the viscous friction between the cell and the channel walls.


Assuntos
Capilares/fisiologia , Pulmão , Modelos Biológicos , Monócitos , Fenômenos Biomecânicos , Humanos , Pulmão/irrigação sanguínea , Pulmão/citologia , Técnicas Analíticas Microfluídicas/instrumentação , Monócitos/citologia , Monócitos/fisiologia , Células THP-1
14.
PLoS One ; 15(6): e0233239, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32516315

RESUMO

Foodborne contamination and associated illness in the United States is responsible for an estimated 48 million cases per year. Increased food demand, global commerce of perishable foods, and the growing threat of antibiotic resistance are driving factors elevating concern for food safety. Foodborne illness is often associated with fresh-cut, ready-to-eat produce commodities due to the perishable nature of the product and relatively minimal processing from farm to the consumer. The research presented here optimizes and evaluates the utility of microfluidic droplets, also termed ultra-miniaturized bioreactors, for rapid detection of viable Salmonella enterica ser. Typhimurium in a shredded lettuce wash water acquired from a major Mid-Atlantic produce processing facility (denoted as Producer) in the U.S. Using a fluorescently-labeled anti-S. Typhimurium antibody and relative fluorescence intensities, paired with in-droplet incubation, S. Typhimurium was detected and identified with 100% specificity in less than 5 h. In initial optimization experiments using S. Typhimurium-spiked sterile water, the relative fluorescence intensity of S. Typhimurium was approximately two times that of the observed relative intensities of five non-S. Typhimurium negative controls at 4-h incubation in droplets containing Rappaport-Vasiliadis (RV) broth at 37°C: relative fluorescence intensity for S. Typhimurium = 2.36 (95% CI: 2.15-2.58), Enterobacter aerogens 1.12 (95% CI: 1.09-1.16), Escherichia coli 700609 = 1.13 (95% CI: 1.09-1.17), E. coli 13706 1.13 (95% CI: 1.07-1.19), E. coli 700891 1.05 (95% CI: 1.03-1.07) and Citrobacter freundii 1.04 (95% CI: 1.03-1.05). S. Typhimurium- and E. aerogens-spiked shredded lettuce wash waters acquired from the Producer were then incubated 4 h in-droplet at 37°C with RV broth. The observed relative fluorescence of S. Typhimurium was significantly higher than that of E. aerogens, 1.56 (95% CI: 1.42-1.71) and 1.10 (95% CI: 1.08-1.12), respectively. While further optimization focusing on compatible concentration methodologies for highly-dilute produce water samples is needed, this application of droplet microfluidics shows great promise in dramatically shortening the time necessary-from days to hours-to confirm viable bacterial contamination in ready-to-eat produce wash waters used throughout the domestic and international food industry.


Assuntos
Microbiologia de Alimentos/métodos , Doenças Transmitidas por Alimentos/prevenção & controle , Técnicas Analíticas Microfluídicas/métodos , Cloro/análise , Citrobacter freundii , Contagem de Colônia Microbiana , Desinfetantes , Escherichia coli O157 , Contaminação de Alimentos/análise , Manipulação de Alimentos/métodos , Indústria de Processamento de Alimentos , Doenças Transmitidas por Alimentos/microbiologia , Microfluídica/métodos , Salmonella typhimurium
15.
Nat Commun ; 11(1): 3111, 2020 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-32561725

RESUMO

Midbrain dopaminergic (DA) axons make long longitudinal projections towards the striatum. Despite the importance of DA striatal innervation, processes involved in establishment of DA axonal connectivity remain largely unknown. Here we demonstrate a striatal-specific requirement of transcriptional regulator Nolz1 in establishing DA circuitry formation. DA projections are misguided and fail to innervate the striatum in both constitutive and striatal-specific Nolz1 mutant embryos. The lack of striatal Nolz1 expression results in nigral to pallidal lineage conversion of striatal projection neuron subtypes. This lineage switch alters the composition of secreted factors influencing DA axonal tract formation and renders the striatum non-permissive for dopaminergic and other forebrain tracts. Furthermore, transcriptomic analysis of wild-type and Nolz1-/- mutant striatal tissue led to the identification of several secreted factors that underlie the observed guidance defects and proteins that promote DA axonal outgrowth. Together, our data demonstrate the involvement of the striatum in orchestrating dopaminergic circuitry formation.


Assuntos
Orientação de Axônios/fisiologia , Axônios/fisiologia , Corpo Estriado/crescimento & desenvolvimento , Neurônios Dopaminérgicos/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Animais , Carbocianinas/administração & dosagem , Corpo Estriado/diagnóstico por imagem , Embrião de Mamíferos , Feminino , Corantes Fluorescentes/administração & dosagem , Peptídeos e Proteínas de Sinalização Intracelular/genética , Microscopia Intravital , Camundongos Knockout , Técnicas Analíticas Microfluídicas , Microinjeções , Microscopia Confocal , Rede Nervosa/fisiologia , Proteínas do Tecido Nervoso/genética , Técnicas de Cultura de Tecidos
16.
Nat Commun ; 11(1): 2982, 2020 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-32532969

RESUMO

Non-invasive and label-free calorimetry could become a disruptive technique to study single cell metabolic heat production without altering the cell behavior, but it is currently limited by insufficient sensitivity. Here, we demonstrate microfluidic single-cell calorimetry with 0.2-nW sensitivity, representing more than ten-fold enhancement over previous record, which is enabled by (i) a low-noise thermometry platform with ultralow long-term (10-h) temperature noise (80 µK) and (ii) a microfluidic channel-in-vacuum design allowing cell flow and nutrient delivery while maintaining a low thermal conductance of 2.5 µW K-1. Using Tetrahymena thermophila as an example, we demonstrate on-chip single-cell calorimetry measurement with metabolic heat rates ranging from 1 to 4 nW, which are found to correlate well with the cell size. Finally, we perform real-time monitoring of metabolic rate stimulation by introducing a mitochondrial uncoupling agent to the microchannel, enabling determination of the spare respiratory capacity of the cells.


Assuntos
Calorimetria/métodos , Técnicas Analíticas Microfluídicas/métodos , Microfluídica/métodos , Análise de Célula Única/métodos , Temperatura , Tetrahymena thermophila/metabolismo , Metabolismo Basal , Calorimetria/instrumentação , Microfluídica/instrumentação , Mitocôndrias/metabolismo , Consumo de Oxigênio , Análise de Célula Única/instrumentação , Tetrahymena thermophila/citologia , Condutividade Térmica
17.
Nat Commun ; 11(1): 2851, 2020 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-32503979

RESUMO

The colonization of surfaces by bacteria is a widespread phenomenon with consequences on environmental processes and human health. While much is known about the molecular mechanisms of surface colonization, the influence of the physical environment remains poorly understood. Here we show that the colonization of non-planar surfaces by motile bacteria is largely controlled by flow. Using microfluidic experiments with Pseudomonas aeruginosa and Escherichia coli, we demonstrate that the velocity gradients created by a curved surface drive preferential attachment to specific regions of the collecting surface, namely the leeward side of cylinders and immediately downstream of apexes on corrugated surfaces, in stark contrast to where nonmotile cells attach. Attachment location and rate depend on the local hydrodynamics and, as revealed by a mathematical model benchmarked on the observations, on cell morphology and swimming traits. These results highlight the importance of flow on the magnitude and location of bacterial colonization of surfaces.


Assuntos
Aderência Bacteriana , Biofilmes/crescimento & desenvolvimento , Escherichia coli/fisiologia , Modelos Biológicos , Pseudomonas aeruginosa/fisiologia , Fenômenos Biomecânicos , Hidrodinâmica , Técnicas Analíticas Microfluídicas , Movimento/fisiologia , Propriedades de Superfície
18.
Elife ; 92020 05 12.
Artigo em Inglês | MEDLINE | ID: covidwho-245716

RESUMO

Platelets are anucleate cells in blood whose principal function is to stop bleeding by forming aggregates for hemostatic reactions. In addition to their participation in physiological hemostasis, platelet aggregates are also involved in pathological thrombosis and play an important role in inflammation, atherosclerosis, and cancer metastasis. The aggregation of platelets is elicited by various agonists, but these platelet aggregates have long been considered indistinguishable and impossible to classify. Here we present an intelligent method for classifying them by agonist type. It is based on a convolutional neural network trained by high-throughput imaging flow cytometry of blood cells to identify and differentiate subtle yet appreciable morphological features of platelet aggregates activated by different types of agonists. The method is a powerful tool for studying the underlying mechanism of platelet aggregation and is expected to open a window on an entirely new class of clinical diagnostics, pharmacometrics, and therapeutics.


Assuntos
Redes Neurais de Computação , Agregação Plaquetária , Citometria de Fluxo , Humanos , Dispositivos Lab-On-A-Chip , Técnicas Analíticas Microfluídicas , Ativação Plaquetária , Trombose/classificação
19.
Elife ; 92020 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-32393438

RESUMO

Platelets are anucleate cells in blood whose principal function is to stop bleeding by forming aggregates for hemostatic reactions. In addition to their participation in physiological hemostasis, platelet aggregates are also involved in pathological thrombosis and play an important role in inflammation, atherosclerosis, and cancer metastasis. The aggregation of platelets is elicited by various agonists, but these platelet aggregates have long been considered indistinguishable and impossible to classify. Here we present an intelligent method for classifying them by agonist type. It is based on a convolutional neural network trained by high-throughput imaging flow cytometry of blood cells to identify and differentiate subtle yet appreciable morphological features of platelet aggregates activated by different types of agonists. The method is a powerful tool for studying the underlying mechanism of platelet aggregation and is expected to open a window on an entirely new class of clinical diagnostics, pharmacometrics, and therapeutics.


Assuntos
Redes Neurais de Computação , Agregação Plaquetária , Citometria de Fluxo , Humanos , Dispositivos Lab-On-A-Chip , Técnicas Analíticas Microfluídicas , Ativação Plaquetária , Trombose/classificação
20.
Nat Commun ; 11(1): 2385, 2020 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-32404937

RESUMO

Upon tissue injury or microbial invasion, a large number of neutrophils converge from blood to the sites of injury or infection in a short time. The migration through a limited number of paths through tissues and capillary networks seems efficient and 'traffic jams' are generally avoided. However, the mechanisms that guide efficient trafficking of large numbers of neutrophils through capillary networks are not well understood. Here we show that pairs of neutrophils arriving closely one after another at capillary bifurcations migrate to alternating branches in vivo and in vitro. Perturbation of chemoattractant gradients and the increased hydraulic resistance induced by the first neutrophil in one branch biases the migration of the following neutrophil towards the other branch. These mechanisms guide neutrophils to efficiently navigate through capillary networks and outline the effect of inter-neutrophil interactions during migration on overall lymphocyte trafficking patterns in confined environments.


Assuntos
Movimento Celular/fisiologia , Fatores Quimiotáticos/metabolismo , Quimiotaxia/fisiologia , Técnicas Analíticas Microfluídicas/métodos , Neutrófilos/fisiologia , Algoritmos , Células Cultivadas , Humanos , Modelos Biológicos , Neutrófilos/citologia , Transdução de Sinais/fisiologia
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