15 research outputs found
Bioinspired Nanoparticulate Medical Glues for Minimally Invasive Tissue Repair
Delivery of tissue glues through small-bore needles or trocars is critical for sealing holes, affixing medical devices, or attaching tissues together during minimally invasive surgeries. Inspired by the granule-packaged glue delivery system of sandcastle worms, a nanoparticulate formulation of a viscous hydrophobic light-activated adhesive based on poly(glycerol sebacate)-acrylate is developed. Negatively charged alginate is used to stabilize the nanoparticulate surface to significantly reduce its viscosity and to maximize injectability through small-bore needles. The nanoparticulate glues can be concentrated to ≈30 w/v% dispersions in water that remain localized following injection. With the trigger of a positively charged polymer (e.g., protamine), the nanoparticulate glues can quickly assemble into a viscous glue that exhibits rheological, mechanical, and adhesive properties resembling the native poly(glycerol sebacate)-acrylate based glues. This platform should be useful to enable the delivery of viscous glues to augment or replace sutures and staples during minimally invasive procedures.United States. National Institutes of Health (GM086433)United States. National Institutes of Health (DE013023
A Portable Chemotaxis Platform for Short and Long Term Analysis
Flow-based microfluidic systems have been widely utilized for cell migration studies given their ability to generate versatile and precisely defined chemical gradients and to permit direct visualization of migrating cells. Nonetheless, the general need for bulky peripherals such as mechanical pumps and tubing and the complicated setup procedures significantly limit the widespread use of these microfluidic systems for cell migration studies. Here we present a simple method to power microfluidic devices for chemotaxis assays using the commercially available ALZET® osmotic pumps. Specifically, we developed a standalone chemotaxis platform that has the same footprint as a multiwell plate and can generate well-defined, stable chemical gradients continuously for up to 7 days. Using this platform, we validated the short-term (24 hours) and long-term (72 hours) concentration dependent PDGF-BB chemotaxis response of human bone marrow derived mesenchymal stem cells.Harvard Stem Cell InstituteNational Institutes of Health (U.S.) (grant HL095722)National Institutes of Health (U.S.) (grant HL097172)Massachusetts Institute of Technology (MIT-UROP program)Massachusetts Institute of Technology (John Reed Fund)National Institute of Biomedical Imaging and Bioengineering (U.S.) (BioMEMS Resource Center (P41 EB 002503)
Sensing the electrical activity of single ion channels with top-down silicon nanoribbons.
Using top-down fabricated silicon nanoribbons, we measure the opening and closing of ion channels alamethicin and gramicidin A. A capacitive model of the system is proposed to demonstrate that the geometric capacitance of the nanoribbon is charged by ion channel currents. The integration of top-down nanoribbons with electrophysiology holds promise for integration of electrically active living systems with artificial electronics
Mass measurements during lymphocytic leukemia cell polyploidization decouple cell cycle- and cell size-dependent growth
© 2020 National Academy of Sciences. All rights reserved. Cell size is believed to influence cell growth and metabolism. Consistently, several studies have revealed that large cells have lower mass accumulation rates per unit mass (i.e., growth efficiency) than intermediate-sized cells in the same population. Sizedependent growth is commonly attributed to transport limitations, such as increased diffusion timescales and decreased surface-to-volume ratio. However, separating cell size- and cell cycle-dependent growth is challenging. To address this, we monitored growth efficiency of pseudodiploid mouse lymphocytic leukemia cells during normal proliferation and polyploidization. This was enabled by the development of large-channel suspended microchannel resonators that allow us to monitor buoyant mass of single cells ranging from 40 pg (small pseudodiploid cell) to over 4,000 pg, with a resolution ranging from ∼1% to ∼0.05%. We find that cell growth efficiency increases, plateaus, and then decreases as cell cycle proceeds. This growth behavior repeats with every endomitotic cycle as cells grow into polyploidy. Overall, growth efficiency changes 33% throughout the cell cycle. In contrast, increasing cell mass by over 100-fold during polyploidization did not change growth efficiency, indicating exponential growth. Consistently, growth efficiency remained constant when cell cycle was arrested in G2. Thus, cell cycle is a primary determinant of growth efficiency. As growth remains exponential over large size scales, our work finds no evidence for transport limitations that would decrease growth efficiency
Cellphone-Enabled Microwell-Based Microbead Aggregation Assay for Portable Biomarker Detection
Quantitative biomarker
detection methods featured with rapidity,
high accuracy, and label-free are demonstrated for the development
of point-of-care (POC) technologies or “beside” diagnostics.
Microbead aggregation via protein-specific linkage provides an effective
approach for selective capture of biomarkers from the samples, and
can directly readout the presence and amount of the targets. However,
sensors or microfluidic analyzers that can accurately quantify the
microbead aggregation are scared. In this work, we demonstrate a microwell-based
microbeads analyzing system, by which online manipulations of microbeads
including trapping, arraying, and rotations can be realized, providing
a series of microfluidic approaches to layout the aggregated microbeads
for further convenient characterizations. Prostate specific antigen
is detected using the proposed system, demonstrating the limit of
detection as low as 0.125 ng/mL (3.67 pM). A two-step reaction kinetics
model is proposed for the first time to explain the dynamic process
of microbeads aggregation. The developed microbeads aggregation analysis
system has the advantages of label-free detection, high throughput,
and low cost, showing great potential for portable biomarker detection
Nanoelectronic Platform for Ultrasensitive Detection of Protein Biomarkers in Serum using DNA Amplification
Silicon nanowire field effect transistors
(NWFETs) are low noise,
low power, ultrasensitive biosensors that are highly amenable to integration.
However, using NWFETs to achieve direct protein detection in physiological
buffers such as blood serum remains difficult due to Debye screening,
nonspecific binding, and stringent functionalization requirements.
In this work, we performed an indirect sandwich immunoassay in serum
combined with exponential DNA amplification and pH measurement by
ultrasensitive NWFET sensors. Measurements of model cytokine interleukin-2
concentrations from <20 fM to >200 pM were demonstrated, surpassing
the conventional NWFET urease-based readout. Our approach paves way
for future development of universal, highly sensitive, miniaturized,
and integrated nanoelectronic devices that can be applied to a wide
variety of analytes