Characterizing asthma from a drop of blood using neutrophil chemotaxis

Sackmann, Eric K.; Berthier, Jean; Schwantes, Elizabeth A.; Fichtinger, Paul S.; Evans, Michael D.; Dziadzio, Laura; Huttenlocher, Anna; Mathur, Sameer K.; Beebe, David J.

doi:10.1073/pnas.1324043111

Cited by 73 publications

(92 citation statements)

References 57 publications

(52 reference statements)

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“…Therefore, the CPI is very low, classifying cell movement as no chemotaxis. In case 4, the directness has a value of 0.35, as in an example reported by Sackmann et al (58). An FMI of 0.3 results in an SMI of 0.18, which leads to a low CPI of 0.21.…”

Section: Statistical Analysis Of Haptotactic Behaviormentioning

confidence: 67%

“…5). Thus, it bears these problems like the FMI with the disregard of the x direction of migration as well (58). Directness weights the migration in x and y direction equally, and only information about the ratio of the path length in x and y direction is considered, whereas the overall direction of migration itself is not examined.…”

Section: Statistical Analysis Of Haptotactic Behaviormentioning

confidence: 99%

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A Haptotaxis Assay for Leukocytes Based on Surface-Bound Chemokine Gradients

Rink

Helmer

et al. 2015

The Journal of Immunology

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The migration of leukocytes in response to chemokine gradients is an important process in the homeostasis of the human immune system and inflammation. In vivo the migration takes place on the surface of the endothelium to which the chemokine gradient is immobilized via interaction with glycosaminoglycans. To study leukocyte migration in response to surface-bound chemokines, we generated chemokine gradients by a simple stamping method: agarose stamps were soaked with chemokine solution to form continuous chemokine gradients by diffusion. These gradients could be easily transferred to a petri dish surface by stamping. We show that neutrophil granulocytes recognize these gradients and migrate toward increasing chemokine concentrations dependent on the slope of the gradient. Single-cell responses were recorded, and statistical analyses of cell behavior and migration were performed. For analysis of chemotaxis/haptotaxis, we propose a chemotactic precision index that is broadly applicable, valid, and allows for a straightforward and rapid quantification of the precision by which cells follow the direction of a given gradient. The presented technique is very simple, cost-efficient, and can be broadly applied for generating defined and reproducible immobilized gradients of almost any protein on surfaces, and it is a valuable tool to study haptotaxis.

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Section: Statistical Analysis Of Haptotactic Behaviormentioning

confidence: 67%

Section: Statistical Analysis Of Haptotactic Behaviormentioning

confidence: 99%

A Haptotaxis Assay for Leukocytes Based on Surface-Bound Chemokine Gradients

Rink

Helmer

et al. 2015

The Journal of Immunology

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“…For accurate diagnosis of asthma, a microfluidic device was recently developed that provides an alternative platform for the clinicians to characterize asthma based on the cellular function. They showed that neutrophils move slower than normal in response to inflammation among asthmatics compared to those with allergic rhinitis [26]. Also, COPD correlates well to neutrophil infiltration into airways through chemo tactic migration.…”

Section: Development Of a Diagnostic Systemmentioning

confidence: 99%

Untitled

2016

IJBSBE

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Revisiting Pulmonary Diseases using Microfluidic IntroductionThe human respiratory system consists of nose, pharynx (throat), larynx (voice box), trachea (windpipe), bronchi, and the lungs [1]. The nose, pharynx, larynx, trachea and bronchi together form the respiratory airways. The bronchus continues to divide within lung into many narrower and shorter airways known as bronchioles [2]. The branching networks of pulmonary airways are lined with a viscous liquid film secreted by airway epithelial cells [3]. Terminal bronchioles are clustered in grapelike sacs, the alveoli. Gaseous exchange between air and blood takes place in the alveoli. The lungs contain approximately 500 million alveoli, each about 200 to 300 μm in diameter. The alveolar wall consists of a single layer of type I alveolar cells. Each alveolus is surrounded by a network of pulmonary capillaries. The interstitial space between pulmonary capillaries and alveolus forms a very thin barrier which facilitates gaseous exchange. Apart from type I alveolar cells, 5 % of the alveolar surface epithelium is covered by type II alveolar cells, which secrete a phosphor lipoprotein complex known as pulmonary surfactant that facilitates lung expansion [2]. In addition to type II alveolar cells, surfactant proteins are also produced by Clara cells of peripheral airways. The pulmonary surfactant produced from these cells is absorbed into the luminal air-liquid interface of the pulmonary airways and thus reduces the surface tension to values as low as zero during expiration. This in turn prevents the airway closure [4]. Lung epithelium is a highly complex tissue where epithelial cells, sub epithelial fibroblasts and the extracellular matrix of the airway wall are intricately involved in maintaining and regulating the structure and function of the lung [5]. Lung diseasesRespiratory diseases and disorders encompass pathological conditions that mostly affect the organs and tissues that take part in gaseous exchange (Figure 1). Notably, such abnormalities affect the airways, the physiology structure of lung tissue, and the pulmonary circulation [6]. The lung diseases are broadly classified into obstructive, restrictive and infectious diseases (Table 1).Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the world. The COPD burden is projected to increase globally in the coming decades because of continued exposure to COPD risk factors and aging of the population [7]. COPD, a chronic inflammatory disease, is generally an adult age problem [8] and characterized by breathing difficulty as a consequence of narrowed airways. Long term exposure of lungs to noxious particles or gases, such as cigarette smoke, is considered as the main cause of COPD. According to WHO, COPD will become third leading cause of death by 2030 [9].Similarly, asthma is also amongst the chronic inflammatory disorders characterized by active hyper responsiveness to a variety of stimuli e.g. airborne allergens. It results from a complex interaction among inflammatory cel...

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“…Microfluidic systems with integrated sensors have been widely used to perform molecular assays on blood samples 24 , capture circulating tumor cells 25 , and detect cancer-specific biomarkers 26 . However, these systems are mainly limited to planar structures and are able to transport liquid over small distances only.…”

Section: Introductionmentioning

confidence: 99%

A toolkit of thread-based microfluidics, sensors, and electronics for 3D tissue embedding for medical diagnostics

et al. 2016

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Threads, traditionally used in the apparel industry, have recently emerged as a promising material for the creation of tissue constructs and biomedical implants for organ replacement and repair. The wicking property and flexibility of threads also make them promising candidates for the creation of three-dimensional (3D) microfluidic circuits. In this paper, we report on thread-based microfluidic networks that interface intimately with biological tissues in three dimensions. We have also developed a suite of physical and chemical sensors integrated with microfluidic networks to monitor physiochemical tissue properties, all made from thread, for direct integration with tissues toward the realization of a thread-based diagnostic device (TDD) platform. The physical and chemical sensors are fabricated from nanomaterial-infused conductive threads and are connected to electronic circuitry using thread-based flexible interconnects for readout, signal conditioning, and wireless transmission. To demonstrate the suite of integrated sensors, we utilized TDD platforms to measure strain, as well as gastric and subcutaneous pH in vitro and in vivo.

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Characterizing asthma from a drop of blood using neutrophil chemotaxis

Cited by 73 publications

References 57 publications

A Haptotaxis Assay for Leukocytes Based on Surface-Bound Chemokine Gradients

A Haptotaxis Assay for Leukocytes Based on Surface-Bound Chemokine Gradients

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A toolkit of thread-based microfluidics, sensors, and electronics for 3D tissue embedding for medical diagnostics

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