Despite their rarity in peripheral blood, basophils play important roles in allergic disorders and other diseases including sepsis and COVID-19. Existing basophil isolation methods require many manual steps and suffer...
Microscale surgery on single cells
and small organisms has enabled
major advances in fundamental biology and in engineering biological
systems. Examples of applications range from wound healing and regeneration
studies to the generation of hybridoma to produce monoclonal antibodies.
Even today, these surgical operations are often performed manually,
but they are labor intensive and lack reproducibility. Microfluidics
has emerged as a powerful technology to control and manipulate cells
and multicellular systems at the micro- and nanoscale with high precision.
Here, we review the physical and chemical mechanisms of microscale
surgery and the corresponding design principles, applications, and
implementations in microfluidic systems. We consider four types of
surgical operations: (1) sectioning, which splits a biological entity
into multiple parts, (2) ablation, which destroys part of an entity,
(3) biopsy, which extracts materials from within a living cell, and
(4) fusion, which joins multiple entities into one. For each type
of surgery, we summarize the motivating applications and the microfluidic
devices developed. Throughout this review, we highlight existing challenges
and opportunities. We hope that this review will inspire scientists
and engineers to continue to explore and improve microfluidic surgical
methods.
Heart development in the chicken embryo is regulated by a concert of cardiogenic morphogens and signaling molecules, but the physiological signal molecule nitric oxide(NO) has not been studied in the context of heart formation. A dynamic investigation of endoderm NO formation demonstrates for the first time a correlation with the established development events of the cardiac heart fields and heart tube. Manipulation of endoderm NO signaling demonstrate a role of NO signaling in the differentiation and proliferation of cardiac progenitors for heart tube formation and cardiac heart field development. To investigate NO in the proliferation of myocardial cells in the heart tube embryos, a computer vision based artificial intelligence approach is followed to automate the long and tedious job of counting cells in a large image dataset. We document NO as an important signaling molecule in the regulation of nascent embryonic cardiogenesis whose effects on other early cardiogenic morphogens is unknown.
Despite their rarity in peripheral blood, basophils play important roles in allergic disorders and other diseases including sepsis and COVID-19. Existing basophil isolation methods require many manual steps and suffer from significant variability in purity and recovery. We report an integrated basophil isolation device (i-BID) in microfluidics for negative immunomagnetic selection of basophils directly from 100 μL of whole blood within 10 minutes. We use a simulation-driven pipeline to design a magnetic separation module to apply an exponentially increasing magnetic force to capture magnetically tagged non-basophils flowing through a microtubing sandwiched between magnetic flux concentrators sweeping across a Halbach array. The exponential profile captures non-basophils effectively while preventing their excessive initial buildup causing clogging. The i-BID isolates basophils with a mean purity of 93.9%±3.6% and recovery of 95.6%±3.4% without causing basophil degradation or unintentional activation. Our i-BID has the potential to enable basophil-based point-of-care diagnostics such as rapid allergy assessment.
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