We demonstrate a low-power (<0.1 mW), low-voltage (<10 Vp-p) on-chip piezoelectrically actuated micro-sorter that can deflect single particles and cells at high-speed. With rhodamine in the stream, switching of flow between channels can be visualized at high actuation frequency (~1.7 kHz). The magnitude of the cell deflection can be precisely controlled by the magnitude and waveform of input voltage. Both simulation and experimental results indicate that the drag force imposed on the suspended particle/cell by the instantaneous fluid displacement can alter the trajectory of the particle/cell of any size, shape, and density of interest in a controlled manner. The open-loop E. Coli cell deflection experiment demonstrates that the sorting mechanism can produce a throughput of at least 330 cells/s, with a promise of a significantly higher throughput for an optimized design. To achieve close-loop sorting operation, fluorescence detection, real-time signal processing, and field-programmable-gate-array (FPGA) implementation of the control algorithms were developed to perform automated sorting of fluorescent beads. The preliminary results show error-free sorting at a sorting efficiency of ~70%. Since the piezoelectric actuator has an intrinsic response time of 0.1–1 ms and the sorting can be performed under high flowrate (particle speed of ~1–10 cm/s), the system can achieve a throughput of >1,000 particles/s with high purity.
A novel design is demonstrated for a solid state, reagent-less sensor capable of rapid and simultaneous measurement of pH and Total Alkalinity (A) using ion sensitive field effect transistor (ISFET) technology to provide a simplified means of characterization of the aqueous carbon dioxide system through measurement of two "master variables": pH and A. ISFET-based pH sensors that achieve 0.001 precision are widely used in various oceanographic applications. A modified ISFET is demonstrated to perform a nanoliter-scale acid-base titration of A in under 40 s. This method of measuring A, a Coulometric Diffusion Titration, involves electrolytic generation of titrant, H, through the electrolysis of water on the surface of the chip via a microfabricated electrode eliminating the requirement of external reagents. Characterization has been performed in seawater as well as titrating individual components (i.e., OH, HCO, CO, B(OH), PO) of seawater A. The seawater measurements are consistent with the design in reaching the benchmark goal of 0.5% precision in A over the range of seawater A of ∼2200-2500 μmol kg which demonstrates great potential for autonomous sensing.
We report here the in vivo combined-modality imaging of multifunctional drug delivery nanoparticles. These dextran core-based stealth liposomal nanoparticles (nanosomes) contained doxorubicin, iron oxide for MRI contrast, and Bodipy for fluorescence. The particles were long-lived in vivo due to surface decoration with polyethylene glycol (PEG) and the incorporation of acetylated lipids which were UV cross-linked for physical stability. We developed a rodent dorsal skinfold window chamber which facilitated both MRI and non-destructive optical imaging of nanoparticle accumulation in the same tumors. Chamber tumors were genetically labeled with DsRed-2 that enabled the MR images, the red fluorescence of the tumor, and the blue fluorescence of the nanoparticles to be co-localized. The nanoparticle design and MR imaging developed with the window chamber were then extended to orthotopic pancreatic tumors expressing DsRed-2. The tumors were MR imaged using iron oxide-dextran liposomes and by fluorescence to demonstrate the deep imaging capability of these nanoparticles.
In recent years, blood coagulation monitoring has become crucial to diagnosing causes of hemorrhages, developing anticoagulant drugs, assessing bleeding risk in extensive surgery procedures and dialysis, and investigating the efficacy of hemostatic therapies. In this regard, advanced technologies such as microfluidics, fluorescent microscopy, electrochemical sensing, photoacoustic detection, and micro/nano electromechanical systems (MEMS/NEMS) have been employed to develop highly accurate, robust, and cost-effective point of care (POC) devices. These devices measure electrochemical, optical, and mechanical parameters of clotting blood. Which can be correlated to light transmission/scattering, electrical impedance, and viscoelastic properties. In this regard, this paper discusses the working principles of blood coagulation monitoring, physical and sensing parameters in different technologies. In addition, we discussed the recent progress in developing nanomaterials for blood coagulation detection and treatments which opens up new area of controlling and monitoring of coagulation at the same time in the future. Moreover, commercial products, future trends/challenges in blood coagulation monitoring including novel anticoagulant therapies, multiplexed sensing platforms, and the application of artificial intelligence in diagnosis and monitoring have been included.
We demonstrate an
autonomous, high-throughput mechanism for sorting
of emulsion droplets with different sizes concurrently flowing in
a microfluidic Hele-Shaw channel. The aqueous droplets of varying
radii suspended in olive oil are separated into different streamlines
across the channel upon interaction with a shallow (depth ∼
700 nm) inclined guiding track ablated into the polydimethylsiloxane-coated
surface of the channel with focused femtosecond laser pulses. Specifically,
the observed differences in the droplet trajectories along the guiding
track arise due to the different scaling of the confinement force
attracting the droplets into the track, fluid drag, and wall friction,
with the droplet radius. In addition, the distance traveled by the
droplets along the track also depends on the track width, with wider
tracks providing more stable droplet guiding for any given droplet
size. We systematically study the influence of the droplet size and
velocity on the trajectory of the droplets in the channel and analyze
the sensitivity of size-based droplet sorting for varying flow conditions.
The droplet guiding and sorting experiments are complemented by modeling
of the droplet motion in the channel flow using computational fluid
dynamics simulations and a previously developed model of droplet guiding.
Finally, we demonstrate a complete separation of droplets produced
by fusion of two independent droplet streams at the inlet of the Hele-Shaw
channel from unfused daughter droplets. The presented droplet sorting
technique can find applications in the development of analytical and
preparative microfluidic protocols.
Early detection is important for many solid cancers but the images provided by ultrasound, magnetic resonance imaging (MRI), and computed tomography applied alone or together, are often not sufficient for decisive early screening ∕ diagnosis. We demonstrate that MRI augmented with fluorescence intensity (FI) substantially improves detection. Early stage murine pancreatic tumors that could not be identified by blinded, skilled observers using MRI alone, were easily identified with MRI along with FI images acquired with photomultiplier tube detection and offset laser scanning. Moreover, we show that fluorescence lifetime (FLT) imaging enables positive identification of the labeling fluorophore and discriminates it from surrounding tissue autofluorescence. Our data suggest combined-modality imaging with MRI, FI, and FLT can be used to screen and diagnose early tumors.
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