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Cambridge, MA, United States

Steinhilber D.,Free University of Berlin | Seiffert S.,Harvard University | Heyman J.A.,Harvard University | Heyman J.A.,HabSel Inc. | And 3 more authors.
Biomaterials | Year: 2011

We report the preparation of polyglycerol particles on different length scales by extending the size of hyperbranched polyglycerols (3 nm) to nanogels (32 nm) and microgels (140 and 220. μm). We use miniemulsion templating for the preparation of nanogels and microfluidic templating for the preparation of microgels, which we obtain through a free-radical polymerization of hyperbranched polyglycerol decaacrylate and polyethylene glycol-diacrylate. The use of mild polymerization conditions allows yeast cells to be encapsulated into the resultant microgels with cell viabilities of approximately 30%. © 2010 Elsevier Ltd. Source

Guo M.T.,Harvard University | Rotem A.,Harvard University | Heyman J.A.,Harvard University | Heyman J.A.,HabSel Inc. | Weitz D.A.,Harvard University
Lab on a Chip - Miniaturisation for Chemistry and Biology | Year: 2012

Droplet microfluidics offers significant advantages for performing high-throughput screens and sensitive assays. Droplets allow sample volumes to be significantly reduced, leading to concomitant reductions in cost. Manipulation and measurement at kilohertz speeds enable up to 108 samples to be screened in one day. Compartmentalization in droplets increases assay sensitivity by increasing the effective concentration of rare species and decreasing the time required to reach detection thresholds. Droplet microfluidics combines these powerful features to enable currently inaccessible high-throughput screening applications, including single-cell and single-molecule assays. This journal is © 2012 The Royal Society of Chemistry. Source

Windbergs M.,Harvard University | Windbergs M.,Saarland University | Windbergs M.,Helmholtz Institute for Pharmaceutical science Saarland | Windbergs M.,Korea Institute of Science and Technology | And 5 more authors.
Journal of the American Chemical Society | Year: 2013

Simultaneous encapsulation of multiple active substances in a single carrier is essential for therapeutic applications of synergistic combinations of drugs. However, traditional carrier systems often lack efficient encapsulation and release of incorporated substances, particularly when combinations of drugs must be released in concentrations of a prescribed ratio. We present a novel biodegradable core-shell carrier system fabricated in a one-step, solvent-free process on a microfluidic chip; a hydrophilic active (doxorubicin hydrochloride) is encapsulated in the aqueous core, while a hydrophobic active (paclitaxel) is encapsulated in the solid shell. Particle size and composition can be precisely controlled, and core and shell can be individually loaded with very high efficiency. Drug-loaded particles can be dried and stored as a powder. We demonstrate the efficacy of this system through the simultaneous encapsulation and controlled release of two synergistic anticancer drugs using two cancer-derived cell lines. This solvent-free platform technology is also of high potential value for encapsulation of other active ingredients and chemical reagents. © 2013 American Chemical Society. Source

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 99.67K | Year: 2009

DESCRIPTION (provided by applicant): We seek to develop a completely new microfluidics-based method (Droplet Compartmentalized Selection - DCS) to isolate cells that produce antibodies with desired binding characteristics. In DCS, individual cells are encapsulated (together with components to assay binding activity) in pico-liter scale droplets, which can then be screened for binding activity at rates of about 1,000 droplets per second. Individual cells will fill the droplets with antibody to (M concentrations within a few hours. A fluorescent read-out can then be used to identify and collect droplets that contain the desired antibody-producing cells. Crucially, there is no need to immortalize the antibody-producing cells. Instead, the antibody-encoding genes can be isolated from individual selected cells by reverse-transcriptase PCR and then cloned into appropriate expression vectors. DCS has three major advantages over typical methods to isolate monoclonal antibodies. 1) Because the screening can be performed on individual, non-immortalized cells, a great deal of time is saved. There is no need to create hybridomas to immortalize the antibody-producing cells, and the time required to grow and assay individual clones is several hours rather than several weeks. 2) DCS allows access to much greater antibody diversity. By eliminating the highly inefficient process of hybridoma generation (typically only 1/100,000 antibody-producing cells are immortalized), and by greatly speeding the screening process, it is possible to screen tens- or hundreds- of thousands of individual cells for the ability to produce desired antibodies. In contrast, a typical monoclonal antibody screen can analyze at most several hundred unique antibody-producing hybridomas. And 3), DCS will allow screening of cell types which are not amenable to typical hybridoma-based methods. For example, cells that produce antibodies against particular targets could be isolated from blood from human patients. This could pave the way for novel diagnostic tests and would facilitate identification of endogenous human antibodies that might serve as building blocks for therapeutic antibodies. PUBLIC HEALTH RELEVANCE: Therapeutic monoclonal antibodies make up the fastest-growing segment of the prescription pharmaceutical market and are the cornerstone of an emerging class of 'targeted' cancer therapies that are designed to prevent tumor growth by more specific actions than older treatments, via the targeting of molecular drivers of carcinogenesis. Our new microfluidics-based method (Droplet Compartmentalized Selection - DCS) to isolate cells that produce antibodies with desired binding characteristics will revolutionize the production of mAbs. It will enable much higher throughput screening, giving far greater access to immune repertoires, thus allowing the isolation of more and better antibody therapeutics. Moreover, because the antibodies from a single cell can be detected, it becomes possible to directly screen non-immortalized cells instead of hybridomas, further increasing the antibody diversity that can be accessed.

Rossow T.,Free University of Berlin | Heyman J.A.,Harvard University | Heyman J.A.,HabSel Inc. | Ehrlicher A.J.,Harvard University | And 7 more authors.
Journal of the American Chemical Society | Year: 2012

Micrometer-sized hydrogel particles that contain living cells can be fabricated with exquisite control through the use of droplet-based microfluidics and bioinert polymers such as polyethyleneglycol (PEG) and hyperbranched polyglycerol (hPG). However, in existing techniques, the microgel gelation is often achieved through harmful reactions with free radicals. This is detrimental for the viability of the encapsulated cells. To overcome this limitation, we present a technique that combines droplet microfluidic templating with bio-orthogonal thiol-ene click reactions to fabricate monodisperse, cell-laden microgel particles. The gelation of these microgels is achieved via the nucleophilic Michael addition of dithiolated PEG macro-cross-linkers to acrylated hPG building blocks and does not require any initiator. We systematically vary the microgel properties through the use of PEG linkers with different molecular weights along with different concentrations of macromonomers to investigate the influence of these parameters on the viability and proliferation of encapsulated yeast cells. We also demonstrate the encapsulation of mammalian cells including fibroblasts and lymphoblasts. © 2012 American Chemical Society. Source

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