Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - colloidlego (IMPACT OF BUIDING BLOCK SHAPE ON SELF-ASSEMBLY KINETICS)

Teaser

Complex structures in nature are often composed from elemental subunits, which are not mounted together by an intelligent designer, instead they spontaneously self-assemble based on protocols \'coded\' in each subunit. Viral capsids are great examples, folding spontaneously...

Summary

Complex structures in nature are often composed from elemental subunits, which are not mounted together by an intelligent designer, instead they spontaneously self-assemble based on protocols \'coded\' in each subunit. Viral capsids are great examples, folding spontaneously through non-covalent interactions between individual protein chains to create perfectly arranged hollow polyhedra. Taking inspiration form the nature and use self-assembly also in man-made systems is a tempting alternative to current manufacture routines, relying mainly on direct ‘pick and place’ techniques.
This project was focusing on development of novel pathways for the synthesis of microscopic building blocks and their subsequent self-assembly into ordered structures. These building blocks are composed from hydrogels — solid materials composed mainly from water, resembling living cells by size, appearance and softness. In the same way to our bodies, built from individual cells, these building blocks were subsequently combined to ordered structures. Mimicking the cellular organization with cell-like hydrogels can provide essential materials for tissue engineering and implantology.

Work performed

First, I developed a method for high throughput synthesis of cell-like hydrogel microparticles, which allows synthesis of microgels of any desired shape. The shape defines the structure of the self-assembly in a similar way as shapes of individual Lego brick defines the structure of an object one builds from those. I found conditions, under which the microgel particles self-assemble into ordered two dimensional structures (Figure1-left). I developed method to ‘glue’ the individual discs of the assembly together and form one sheet. By tuning the conditions of the gluing, the sheet either remains flat, or buckles to a bowl shape or a roll (Figure 1-right), thus sheets of various desired shapes can be easily produced to fulfill the requirements of a specific application. Because the assembled structure contains voids between individual discs, the resulting sheet contains also voids — pores. The developed method provides convenient synthesis of hydrogel sheets with defines pore sizes through self-assembly. In collaboration with researchers from the Department of Pharmaceutical Sciences we work on application of these highly defined porous membranes as supports for kidney cells with future application in the manufacture of artificial kidney. This collaboration already led to a joint publication on the SFL synthesis of biodegradable microgels.
Presented self-assembled membranes, constructed from responsive hydrogels, can work as actuators and are promising in soft-microrobotics, artificial muscle construction or hybrid hydrogel-living systems. Thanks to the self-assembly, such actuators can be built remotely for example in inaccessible areas.
The ability to build ordered structures through self-assembly of hydrogel microparticles opened a way to self-assembled organized hydrogel structures, however the complexity of available structures is limited. Therefore, I focused on alternative ways of organizing microscaled hydrogels. I developed hydrogel microrobots, that crawl over a solid surface and manipulate other microobjects in a controlled manner. The locomotion principle of the developed crawlers is fundamentally new, allowing simple driving and steering of the crawler with visible light. Due to their soft hydrogel nature, these robots can be used for precise manipulation with mechanically sensitive objects for example in single cell analysis or in-vitro fertilization techniques. I plan to use these crawlers as microscopic builders of organized hydrogel structures (Figure 2). I am convinced, that the combination of demonstrated self-assembly and directed assembly principles is the key for simple, affordable yet precise construction of hydrogel structures, organized on microscale, currently needed (among others) in tissue engineering applications.

Overview of the dissemination and explotation of the results:
List of conferences attended: CHAINS 2016 – Poster presentation, Soft Matter Meeting 2017 – Oral presentation, LIQUIDS 2017 – Poster presentation, Micromotors Dresden 2017 – Poster presentation, Utrecht Chemistry Days 2017 – Poster presentation (best poster award), IACIS 2018 – Oral presentation (confirmed)

The work on biodegradable microgels, acknowledging the EC funding was published in the Small journal (Jimp = 8.6).
Rehor, I.; van Vreeswijk, S.; Vermonden, T.; Hennink, W. E.; Kegel, W. K.; Eral, H. B. Biodegradable Microparticles for Simultaneous Detection of Counterfeit and Deteriorated Edible Products. Small 2017, 13 (39).

The fulltext can be find in the open repository of the Utrecht University: (https://www.narcis.nl/publication/RecordID/oai%3Adspace.library.uu.nl%3A1874%2F358594/id/2/Language/EN/uquery/rehor/coll/publication)

The research was highlighted on the cover of the journal and in the following media: Advanced Science, TU Delft website, De Ingenieur, NPT, University of Utrecht website
At least two more publications are planned, one on the soft microrobots (manuscript is almost ready and the

Final results

The MC fellowship project has large application potential in emerging fields, as soft (micro)robotics or tissue engineering and it is expected to lead to directly applicable results in forcoming years. Part of the project -biodegradable microgels - already gained attention by industrial subjects. Frisland Campina – the largest Dutch diary producing company is interested to implement this technology to trace their products in the supply chain and financially supports the research on directly applicable technology in the group of Prof. Eral. Successful implementation of this technology will efficiently fight against food and pharmaceutical products counterfeiting that represents severe global problem (up to 10 % of pharmaceuticals worldwide are counterfeits). Furthermore the developed microgels report on degustation safety of the product, through detection of microbial contamination or improper storage conditions. Pathogen contamination and growth inside a product is a major concern, especially with foods. In USA only, 48 million people get sick, 128 000 are hospitalized, and 3000 die from foodborne diseases every year . The number of casualties worldwide reaches an alarming 420 000 every year .

Website & more info

More info: https://www.uu.nl/staff/default.aspx.