RESUMEN
Thermal bubble-driven micro-pumps are an upcoming micro-actuator technology that can be directly integrated into micro/mesofluidic channels, have no moving parts, and leverage existing mass production fabrication approaches. These micro-pumps consist of a high-power micro-resistor that boils fluid in microseconds to create a high-pressure vapor bubble which performs mechanical work. As such, these micro-pumps hold great promise for micro/mesofluidic systems such as lab-on-a-chip technologies. However, to date, no current work has studied the interaction of these micro-pumps with biofluids such as blood and protein-rich fluids. In this study, the effects of organic fouling due to egg albumin and bovine whole blood are characterized using stroboscopic high-speed imaging and a custom deep learning neural network based on transfer learning of RESNET-18. It was found that the growth of a fouling film inhibited vapor bubble formation. A new metric to quantify the extent of fouling was proposed using the decrease in vapor bubble area as a function of the number of micro-pump firing events. Fouling due to egg albumin and bovine whole blood was found to significantly degrade pump performance as well as the lifetime of thermal bubble-driven micro-pumps to less than 104 firings, which may necessitate the use of protective thin film coatings to prevent the buildup of a fouling layer.
Asunto(s)
Incrustaciones Biológicas , Incrustaciones Biológicas/prevención & control , Animales , Bovinos , Albúminas , Dispositivos Laboratorio en un Chip , Albúmina Sérica Bovina/químicaRESUMEN
The ability to study chemical dynamics on ultrafast timescales has greatly advanced with the introduction of X-ray free electron lasers (XFELs) providing short pulses of intense X-rays tailored to probe atomic structure and electronic configuration. Fully exploiting the full potential of XFELs requires specialized experimental endstations along with the development of techniques and methods to successfully carry out experiments. The liquid jet endstation (LJE) at the Linac Coherent Light Source (LCLS) has been developed to study photochemistry and biochemistry in solution systems using a combination of X-ray solution scattering (XSS), X-ray absorption spectroscopy (XAS), and X-ray emission spectroscopy (XES). The pump-probe setup utilizes an optical laser to excite the sample, which is subsequently probed by a hard X-ray pulse to resolve structural and electronic dynamics at their intrinsic femtosecond timescales. The LJE ensures reliable sample delivery to the X-ray interaction point via various liquid jets, enabling rapid replenishment of thin samples with millimolar concentrations and low sample volumes at the 120 Hz repetition rate of the LCLS beam. This paper provides a detailed description of the LJE design and of the techniques it enables, with an emphasis on the diagnostics required for real-time monitoring of the liquid jet and on the spatiotemporal overlap methods used to optimize the signal. Additionally, various scientific examples are discussed, highlighting the versatility of the LJE.
RESUMEN
Solid tumors generally exhibit chromosome copy number variation, which is typically caused by chromosomal instability (CIN) in mitosis. The resulting aneuploidy can drive evolution and associates with poor prognosis in various cancer types as well as poor response to T-cell checkpoint blockade in melanoma. Macrophages and the SIRPα-CD47 checkpoint are understudied in such contexts. Here, CIN is induced in poorly immunogenic B16F10 mouse melanoma cells using spindle assembly checkpoint MPS1 inhibitors that generate persistent micronuclei and diverse aneuploidy while skewing macrophages toward a tumoricidal 'M1-like' phenotype based on markers and short-term anti-tumor studies. Mice bearing CIN-afflicted tumors with wild-type CD47 levels succumb similar to controls, but long-term survival is maximized by SIRPα blockade on adoptively transferred myeloid cells plus anti-tumor monoclonal IgG. Such cells are the initiating effector cells, and survivors make de novo anti-cancer IgG that not only promote phagocytosis of CD47-null cells but also suppress tumor growth. CIN does not affect the IgG response, but pairing CIN with maximal macrophage anti-cancer activity increases durable cures that possess a vaccination-like response against recurrence.