Self-assembled virus-like vectors for stem cell phenotyping
|Kind||Collaborative Project, FP7-NMP-2012-SMALL-6|
|Funding||3.9 Mio. €|
The Self-Assembled Virus-like Vectors for Stem Cell Phenotyping (SAVVY) project relies on hierarchical, multi-scale assembly of intrinsically dissimilar nanoparticles to develop novel types of multifunctional Raman probes for analysis and phenotyping of heterogeneous stem cell populations.
Our project will address a large unmet need, as stem cells have great potential for a broad range of therapeutic and biotechnological applications. Characterization and sorting of heterogeneous stem cell populations has been intrinsically hampered by (1) lack of specific antibodies, (2) need for fluorescence markers, (3) low concentration of stem cells, (4) low efficiencies/high costs.
Our technology will use a fundamentally different approach that (1) does not require antibodies, aptamers, or biomarkers, (2) is fluorescence-label free, and (3) is scalable at acceptable cost. The approach uses intrinsic differences in the composition of membranes of cells to distinguish cell populations. These differences will be detect by SERS and analysed through multicomponent analysis.
We have combined the necessary expertise to tackle this challenge: Stellacci has developed rippled nanoparticles that specifically interact with and adhere to cell membranes (analogues to cell penetrating peptides). Lahann has developed bicompartmental Janus polymer particles that have already been surface-modified with rippled particles and integrate specifically in the cell membrane (analogues to viruses). Liz-Marzan has developed highly Raman-active nanoparticles and has demonstrated their selectivity and specificity in SERS experiments. These Raman probes will be loaded into the synthetic viruses to enable membrane fingerprinting. Stevens has developed a Bioinformatics platform for fingerprinting of stem cell populations using cluster analysis algorithms. The effort will be joined by two SME, ChipShop and OMT, that will be able to develop the necessary microfluidic and Raman detection hardware.
SAVVY reporters based on hierarchical self-assembly of disparate components collect Raman cell signatures. Top right: Confocal reconstruction showing Janus vectors loaded with rippled particles bind to cell membrane; Bottom: Savvy Sorter and cell phenotyping concept.
For more see: http://savvyproject.eu/
SURMOF-EU Project 2006-2009
Anchoring of metal-organic frameworks, MOFs, to surfaces
|Kind||Specific Targeted Research Project (STREP)|
|Funding||2.5 Mio. €|
Control of growth and properties of structures on a length scale down to molecular dimensions is one of the major challenges in nanotechnology. The project tackles this challenge by merging surface science with coordination chemistry.
Metal-organic frameworks (MOFs) which are coordination polymers consisting of organic ligands linked together by metal ions, are very promising systems due to the virtually unlimited flexibility in their design. Besides appealing properties of the MOF framework itself which makes MOFs most interesting as electrochromic, magnetic, and storage materials, it is the fact that the framework can be loaded with other molecular compounds by employing a guest-host chemistry which creates a tremendous technological potential in a variety of different fields, in particular with respect to catalysis and hydrogen storage. Further applications, e.g., in sensors and in electronics where the length scale below 20 nm requires solutions beyond established concepts, emerge when MOFs are attached to surfaces.
Contrasting existing strategies which are based on the anchoring of bulk-synthesised MOFs on a surface, the present project takes a qualitatively new approach by using surfaces to initiate and control the growth of MOFs. Combining a bottom-up (building of the MOFs from molecular subunits) with a top-down (different types of lithographies) approach, control of MOF patterns in three dimensions is envisaged.
Involving coordination and synthetic organic chemistry, surface science, and modelling a comprehensive approach is adopted. Ranging from fundamental aspects of nucleation and growth of MOFs to application related issues of their host-guest chemistry different schemes will be explored by experiments on different types of MOFs under conditions which range from ultrahigh vacuum to electrochemical environment.
Although the main focus of the project is on fundamental aspects of a previously unexplored scientific subject we will investigate the applicability of MOF structures with regard to sensing applications. These structures will be based on metal-nanoparticle loaded MOFs which are anchored to a patterned organic surface.
Summer 2008: Mid-term Status of the Project
The overall goal of the SURMOF project is the anchoring of metal organic frameworks (MOFs) on appropriately functionalized solid substrates, their loading with metal organic precursors and the subsequent conversion of these metal organic precursors to metal nanoparticles contained within the MOFs. The final goal of the project is to realize a prototype sensor device utilizing these metal nanoparticles. After the first 18 months of the project already significant progress has been made.
micro-CP stamp showing the SURMOF lettering The most important progress achieved in the first 18 months clearly is the development of a new (so called layer-by-layer) method to deposit MOFs on solid surfaces which goes significantly beyond the crystallization and grafting method which was known before the project started.
Also the implementation of surface plasmon resonance to monitor the deposition of MOFs on substrates has been a full success. The loading of the MOFs with metal organic precursors and their subsequent conversion to metal nanoparticles have also been optimized and further developed. Also with regard to the anchoring of the MOROF subunit on organic surfaces the achieved progress has been documented already.
For the second part of the project it is crucial that SURMOFs based on LBMOFs and MOROFs were already produced or that their successful generation is foreseeable. This goal has clearly been reached. In the case of MOROFs the first layer has already been successfully anchored. The optimization of further deposition is under progress.
A micro-contact-printing stamp showing the "SURMOF" lettering
The electrochemical characterization of metal-organic frameworks (MOFs) deposited on organic surfaces (SURMOFs) also represents an important step in the project. Electrochemical investigations where performed on an LBMOF consisting of Cu(II)/1,3,5-benzene tricarboxylic acid (BTC) and MOF-5 ([Zn4O(bdc)3], (bdc 1,4-benzene-dicarboxylate) and its electrochemical stability was successfully demonstrated.