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Nanoscale cell-on-a-chip: optically interrogated micro-fluidic chip for evaluation of live immobilised prostate cancer cells

Supervised by Dr Patricia Scully with Prof Peter Fielden and Dr Peter Gardner (School of Chemical Engineering and Analytical SciencE

The project aims to interrogate cells incorporated into porous nanostructured polymers, control or perturb their environment, and perform spectroscopic and analytical measurements on the cell response using integrated microfluidic-photonic circuits.

The project will:

  • interrogate live cells at interfaces of inorganic-organic hybrid materials
  • integrate microfluidic and optical structures to create interconnected, 3D fluidic and optical circuits
  • control and measure cellular nutrients, toxins and products using microfluidic analytical techniques
  • evaluate new optical and spectroscopic techniques incorporating nanoparticles, quantum dots etc to measure nanoscale cell interactions

Key deliverables include:

  • development of a 3-D nanoscale system to mimic, alter and measure the biological environment
  • interfacing live cells with optical systems to create a “cell-on-a-chip” device with applications in drug delivery, cancer studies, environmental monitoring and tissue engineering

Live cells will be immobilized within a porous polymer matrix, such as a sol-gel containing growth medium and its vital functions and products will be interrogated via a 3-D miniature optical circuit that is written into undoped clinical grade polymethyl methacrylate (PMMA) using femtosecond laser processing techniques pioneered by Scully1 to create refractive index structures. This will enable light from a range of novel light sources available in the Photon Science Institute to be coupled using optical fibres, to the cell and collected and guided to state of the art detectors/spectrometers, enabling real time experiments to take place and be monitored on the nanoscale.

Using techniques pioneered in the Manchester Interdisciplinary Biocentre by Fielden, the PMMA will be injection moulded into a microfluidic structure so that the cellular environment can be controlled and minute analyte volumes measured in real-time. The polymer matrix could be used to trap viable enzymes, antibodies etc and monitor the influx and efflux of drugs and contaminants through the cells and other organisms.

The cells will be tagged to enable optical detection of biomarkers. For example nanoparticles such as fluorophore-laden silica beads and gold-nanoshell-based immunoassays. Fluorescent nanoparticles have been used for an ultrasensitive DNA-detection system and quantum dot bioconjugates with targeting antibodies have been used to recognize molecular signatures2. Nanoparticles have the advantages of stability and‘tunability’, in that quantum dots do not ‘photobleach’, and nanoparticles with different optical signatures may be conjugated with antibodies to different molecular targets, enabling mapping and real-time monitoring of various molecular markers in a single cell, cell population or tissue is generated; enabling identification of the conjugate markers, their tissue distribution and facilitating new protocols that include cell surface, endocellular and microenvironmental antigens in the same test. Electrokinetic and electrophoresis techniques will be used to move cells, apply stresses to cell membranes and selectively trap a specific type of cell, subcellular organelle, protein, or DNA.3

Femtosecond lasers in the PSI can be used to nanostructure or photomodify optical surfaces to provide an optically and chemically active surface to facilitate interaction with biological materials, for interrogation. 3D optical structures using building blocks like waveguides, gratings, Y splitters etc can provide input paths for optical interrogation of the cell matrix from light sources and detectors.

References:

1. Alexandra Baum, Patricia J Scully, Walter Perrie, Valerio Lucarini (2010). Mechanisms of femtosecond laser induced refractive index modifcation of poly(methyl methacrylate). JOSA B, Vol. 27, Issue 1, pp. 107-111.

2. M Ferrari (2005). Cancer nanotechnology; opportunities and challenges. Nature Reviews; Cancer, 161-172.

3. B P Helmke and A R Minerick (2006). Designing a nano-interface in a microfluidic chip to probe living cells: Challenges and perspectives. PNAS, April 25, 2006, 103, (170) 6419–6424.

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