BPSI Dec 2013 - BIO-SENS-A: Biologically-modified Surface ENgineered Silicon Arrays

Project: Other projectOther internal award

Project Details

Layman's description

Biochemical and biomedical research is moving far beyond the realms of static, single cell behavior. Today, a detailed understanding of how, when and where multi-cellular tissues change is becoming increasingly important. For example inflammation, initiation of the immune response and the spread of cancer all involve cellular signaling processes that occur dynamically. On a molecular level, biologists are beginning to identify and characterize the many secreted proteins which play a crucial role in enabling cells to communicate. We are already applying this knowledge to develop silicon photonic sensor arrays that let us “phone-tap” cellular “chatter”, and provide high-resolution maps of when and where these molecules are secreted. Our current sensor is however limited; although a large number of proteins control the function of a cell, currently we can only decorate the sensor with one antibody, and therefore only sense one protein. If we can develop biological chemistry methods for site-controlled immobilization of antibodies onto a silicon surface, we will be able to build a templated ‘array’: a highly parallel system that allows us to sense many different proteins simultaneously, in real-time and in-situ. This proposal seeks support for this chemical study which will extend an existing physics-electronics collaboration to establish fundamental methodology to underpin a novel biophysical tool.

Key findings

We now have two key results:
1. We have developed a robust methodology for electrically controlling the binding of molecules to silicon surfaces so we can now achieve site-selective silicon modification.
2. We have proven that we can detect chemical binding events using the change in the silicon photonic resonances.
Parkin will present these results at the BPSI symposium in December.

Moving forward, our aim is to combine these findings to build a device which demonstrates that we can site-specifically bind single-strand DNA-1 to silicon region-A and single-strand DNA-2 to silicon region-B. We will then diagnose the presence of the complementary DNA strands to 1 and 2 in a flow mixture passing over the silicon sensor. We plan to publish these results in a multi-disciplinary publication such as Lab on a Chip (impact factor 5.748).

The experiments described are planned to prove that silicon can be developed as a bio-sensing array. This is an important result because unlike competing surface binding-detection technologies which are based on very expensive solid state substrates (quartz crystal in QCM-D and gold chip in SPR) silicon is a cheap and widely available material. Photonic detection technology can also be made affordable and is miniturisable and so silicon diagnosis technology could be a platform for delivering an instantaneous bedside diagnosis instrument which profiles an illness, for example “fingerprinting” a bacterial infection. To support this vision we will submit a multi-postdoc interdisciplinary grant application to the EPSRC grant specifically to develop silicon- adhiron (protein aptamer) arrays because adhiron screening has already been proven as a platform for finding highly specific bio-marker binding molecules.

A successful application which was partly inspired by the collaborations initiated by this project:
Strategic Capital Research Priming Fund of £107k for the project “‘QCM-D: An inter-disciplinary tool for characterising both the structure and function of surface immobilised molecular and biomolecular layers’”

This project has initiated collaboration between Parkin (Chemistry), Johnson (Electronics) and Krauss (Physics). This cross-departmental combination of three researchers was a foundation stone for the development of the University of York Antimicrobial Away Day (July 1st/2nd) co-organised by Maggie Smith, Rachel Curwen and Alison Parkin and involving staff from Biology, Chemistry, Environment and HYMS.

An application partly inspired by the collaborations initiated by this project:
Expression of Interest “Novel technologies for Diagnostics” submitted to the MRC and cofunders call on Antimicrobial Resistance - A Thematic approach: Theme 2 Accelerating therapeutic and diagnostics development. PI: Prof Thomas Krauss and including Alison Parkin and Steve Johnson as co-Is.

A directly related research council grant will follow publication of the work.

N/A, please see above for publication plans
Effective start/end date17/12/1331/07/14