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Receptomics: human sensations on a chip

What if we could measure flavour or scent with a chip? Our experts developed a microfluidic technique called receptomics. This technique measures the response of many different receptor proteins to series of extracts or pure substances in a flow cell, and predicts responses in the human body, thus reducing the need for test panels or animal experiments. The receptomics technique may also be useful for the development of personalised food and medication.

How does receptomics work?

The receptor coding genes are printed in a grid layout of approximately one square centimetre onto a glass slide. A cell layer is seeded on top of the glass slide and the cells attach to the printed DNA. When the cells absorb the DNA via reverse transfection, a living cell array is formed where each spot of the array expresses an unique receptor.

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Using receptor signals

Receptors (GPCR’s and ion channels) have many different biological functions in the human body like the detection of taste or scent molecules and hormones. These molecules are captured on the outside of the cell and they subsequently trigger a biological response inside of the cell. Those intracellular signals can be diverse but often involve calcium ions.

Visualising taste or hormone differences

Our receptomics technique visualizes the changes in calcium ion concentration within the cells of the entire living cell array. We visualize the real-time calcium signals of all array spots in parallel to determine specific response patterns for each sample. In that way we are able to capture for example taste differences in food stuffs like tomato, coffee or beer or hormone differences in blood serum.

A crucial tool in our receptomics technique is the software that allows for the rapid analysis of the signals and statistical tools to report receptor specific differences between samples.

Schematic overview of array preparation and measurement in the microfluidic system.
Schematic overview of array preparation and measurement in the microfluidic system.

Sensing hormones from gut cells

We run receptomics projects focusing on tongue-on-a-chip, nose-on-a-chip and gut-on-a-chip applications. In the case of the gut-on-a-chip application the receptomics chip is placed downstream of gut cells to sense the hormones that are secreted from the gut cells upon stimulation.

Publications

  1. Roelse M, Wehrens R, Henquet MGL, Witkamp RF, Hall RD, Jongsma MA (2019) The effect of calcium buffering and calcium sensor type on the sensitivity of an array-based bitter receptor screening assay. Chemical Senses 44: 497-505.
  2. Roelse M, Receptomics, design of a microfluidic receptor screening technology
  3. Wehrens R, Roelse M, Henquet M, van Lenthe M, Goedhart P, Jongsma MA (2019) Statistical models discriminating between samples measured with microfluidic receptor cell arrays. PLOS One 14(4): e0214878
  4. Roelse M, Henquet MGL, Verhoeven HA, de Ruijter NCA, Wehrens R, van Lenthe MS, Witkamp RF, Hall RD and Jongsma MA (2018) Calcium imaging of GPCR activation using arrays of reverse transfected HEK293 cells in a microfluidic system. Sensors 18, 602
  5. Henquet MGL, Roelse M, de Vos RCH, Schipper A, Polder G, Verhoeven HA, de Ruijter NCA, Jongsma MA (2016) Metabolomics meets functional assays: coupling LCMS and microfluidic cell-based receptor-ligand analyses. Metabolomics 12: 1-13
  6. Srivastava S, Ramaneti R, Roelse M, Vrouwe EX, Brinkman A, de Smet LCPM, van Rijn C, Jongsma MA (2015) A generic microfluidic biosensor of G protein-coupled receptor activation – impedance measurements of reversible morphological changes of reverse transfected HEK293 cells on micro-electrodes. RSC Advances 5, 52563-52570.
  7. Roelse M, de Ruijter NCA, Vrouwe EX, Jongsma MA (2013) A generic microfluidic biosensor of G protein-coupled receptor activation - monitoring cytoplasmic [Ca2+] changes in human HEK293 cells. Biosensors and Bioelectronics 47: 436-444
  8. Laborde C, Pittino F, Verhoeven HA, Lemay SG, Selmi L, Jongsma MA, Widdershoven FP (2015) Real-time imaging of microparticles and living cells with CMOS nanocapacitor arrays. Nature Nanotechnology 10: 791-795.