TECHNOLOGY

In sickle cell disease (SCD), hemoglobin molecules polymerize intracellularly and lead to a cascade of events resulting in decreased deformability and increased adhesion of red blood cells (RBCs). Decreased deformability and increased adhesion of sickle RBCs lead to blood vessel occlusion (vaso-occlusion) in SCD patients. Here, we present a microfluidic approach integrated with a cell dimensioning algorithm to analyze dynamic deformability of adhered RBC at the single-cell level in controlled microphysiological flow. We measured and compared dynamic deformability and adhesion of healthy hemoglobin A (HbA) and homozygous sickle hemoglobin (HbS) containing RBCs in blood samples obtained from 24 subjects. We introduce a new parameter to assess deformability of RBCs: the dynamic deformability index (DDI), which is defined as the time-dependent change of the cell's aspect ratio in response to fluid flow shear stress. Our results show that DDI of HbS-containing RBCs were significantly lower compared to that of HbA-containing RBCs. Moreover, we observed subpopulations of HbS containing RBCs in terms of their dynamic deformability characteristics: deformable and non-deformable RBCs. Then, we tested blood samples from SCD patients and analyzed RBC adhesion and deformability at physiological and above physiological flow shear stresses. We observed significantly greater number of adhered non-deformable sickle RBCs than deformable sickle RBCs at flow shear stresses well above the physiological range, suggesting an interplay between dynamic deformability and increased adhesion of RBCs in vaso-occlusive events.

The objective of this study was to create a method for studying cell–matrix interactions in a physiologically relevant 3D protein-based tissue construct that could be scaled up to perform large-scale screens, study cell–matrix interactions on a population basis, or be remodeled by cells to build larger tissues. We have developed an easy-to-use method to miniaturize protein-based tissue constructs that maintains the 3D in vitro environment, while alleviating several obstacles associated with larger avascular tissue constructs. In this study, we demonstrate that (i) cells can interact with the 3D environment both while encapsulated or while interacting only with the surface of the microtissues, (ii) encapsulated cells are highly viable and, for the first time, (iii) microtissues on this size scale (~200 μm) can be used to quantify cell contractility. This versatile platform should facilitate large-scale screens in 3D in vitro culture conditions for drug development and high throughput mechanistic biology.

Sorting of target cells from complex cellular samples into a high-purity product is challenging yet essential for downstream cell biology research and clinical diagnostics. Inertial microfluidics is an emerging technology attracting a lot of interest for passive and label-free sorting of cells with high throughput. Here, we introduce an inertial microfluidic device based on our vortex sorting platform for continuous size-based double sorting and purification of the larger target cells from the smaller background cells. Our device uses a microscale chamber with three outlets as a sorting unit, and integrates it into a specific topology to enable double sorting and purification functionalities. With properly designed fluidic resistance network and optimized flow conditions, we demonstrated continuous sorting of spiked human cancer stem-like cells from human blood with >90% efficiency and >1,500× enhanced purity, as well as removal of red blood cells with ~99.97% efficiency. We envision this integrated vortex-aided sorter can serve as a viable tool for size-based sorting of large target cells from complex cellular samples. Furthermore, this vortex-aided sorting platform can be integrated into more sophisticated topology with versatile functions for other cell sorting applications.

Microbial fuel cells have gained popularity as a viable, environmentally friendly alternative for the production of energy. However, the challenges in miniaturizing the system for application in smaller devices as well as the short duration of operation have limited the application of these devices. Here, the capillary motion was employed to design a self-pumped paper-based microbial fuel cell operating under continuous flow condition. A proof-of-concept experiment ran approximately 5 days with no outside power or human interference required for the duration of operation. Shewanella oneidensis MR-1 was used to create a maximum current of 52.25 µA in a 52.5 µL paper-based microfluidic device. SEM images of the anode following the experiment showed biofilm formation on the carbon cloth electrode. The results showed a power density of approximately 25 W/m³ and proved unique capabilities of the paper-based microbial fuel cells to produce energy for an extended period of time.

Neutrophil migration and chemotaxis are fundamentally important biological processes and have direct relevance to various health problems. Microfluidic devices provide useful experimental tools for the quantitative analysis of neutrophil chemotaxis in controlled microenvironments. However, such experiments often require specialized research facilities and lengthy cell preparation from a large amount of blood. In this paper, we report a new, yet simple, all-on-chip method for the magnetic isolation of untouched neutrophils directly from small volumes of blood, followed by chemotaxis testing on the same microfluidic device. Furthermore, we incorporated a cell-docking structure to the microfluidic device for better control of the cells’ initial positions before the chemotaxis test and for improved data analysis. The whole experiment can be performed in less than 25 minutes. We successfully validated this method by testing neutrophil chemotaxis to both purified chemoattractant (i.e. fMLP) and clinical samples (sputum from patients with Chronic Obstructive Pulmonary Disease, COPD). Thus, the “all-on-chip” method can be a useful tool for research and clinical applications that require rapid and accurate chemotaxis testing of untouched neutrophils.

Droplet actuation is an essential mechanism for droplet-based microfluidic systems. On-demand electromagnetic actuation is used in a ferrofluid-based microfluidic system for water droplet displacement. Electropermanent magnets (EPMs) are used to induce 50 mT magnetic fields in a ferrofluid filled microchannel with gradients up to 6.4 × 10⁴ kA/m². Short 50 µs current pulses activate the electropermanent magnets and generate negative magnetophoretic forces that range from 10 to 70 nN on 40 to 80 µm water-in-ferrofluid droplets. Maximum droplet displacement velocities of up to 300 µm/s are obtained under flow and no-flow conditions. Electropermanent magnet-activated droplet sorting under continuous flow is demonstrated using a split-junction microfluidic design.

One of the critical challenges in engineering is the wireless transfer of energy to power miniaturized electronic devices that have sizes smaller than the wavelength of electromagnetic radiation. Here, we describe a strategy to self-fold three-dimensional (3D) low gigahertz responsive antennas with small form factors using capillary forces. The antennas are sub-millimeter (500 × 500 × 500 (m³) cubic devices with small form factors and hollow free space in their interior which could be used to embed other devices. We characterize and demonstrate the efficacy of these antennas in dispersive media. Remarkeably, we observe significantly higher power transfer with over an order of magnitude higher transfer efficiency as compared to similarly shaped planar antennas. Moreover, we show that the antennas can transfer on the order of 30 mW to power an LED, highlighting proof of concept for practical applications. Our findings suggest that self-folding polyhedral microantennas could provide a viable solution for powering tiny microdevices.

Here we present the first generation of two-photon beta cell specific in vivo imaging probes based on GLP1R targeting peptides. Among the three compounds of potential interest, we found quite unexpectedly that a squarine-rotaxane conjugate (2PEx-647) had near ideal in vivo imaging characteristics.