Liquid Biopsy

ImmUniverse is particularly keen to understand the role of the crosstalk of tissue and immune cells in progression/remission of ulcerative colitis and atopic dermatitis and to correlate tissue-derived signatures with circulating signatures detectable in liquid biopsies, using omics technologies.

One main challenge of ImmUniverse is to evaluate whether the non-invasive technologies, dermal open-flow microperfusion in the skin and low-intensity pulsed ultrasound stimulation in the gut, can be used as disruptive liquid biopsy technologies, in a translational setting to establish specific disease signatures in blood and explore novel technologies to overcome currently invasive approaches and improving patient compliance, respectively.

Dermal open-flow microperfusion (dOFM)

dOFM is a minimally invasive in-vivo technique using macroscopic probes placed in the dermis to sample interstitial fluid. Probes are inserted about 0.8 mm deep, running parallel to the skin. A precise fluidic pump maintains a constant flow of perfusate within the probe at 1 μl/min. A specific exchange area in the dermis allows for interchange between perfusate and interstitial fluid, capturing various tissue components, including lipophilic substances, large molecules like anti bodies, and mobile cells. dOFM enables monitoring time-dependent processes hourly, with each sampling session lasting up to 72 hours.

This can be repeated as needed, facilitating baseline and pharmacodynamic response assessment following a stimulus, such as treatment. Both dOFM and blood sampling will be conducted over 8 hours, adhering to the defined sequence.

Take a closer look at the Dermal open-flow microperfusion (dOFM) in the video below.

Our members Thomas Birngruber from Joanneum Research and Dora Stölzl from University Hospital Kiel explain the method. Elliot Grünberg, who lives with atopic dermatitis, shares his personal experience of the method.

Low-intensity pulsed ultrasound (LIPUS)

LIPUS has been employed to release cell vesicles and molecules, hinting at the potential for non-invasive localized stimulation of patients‘ damaged tissue microenvironment. This may trigger specific factor release from cells, which could then be carried by the lymphatic system into the peripheral blood, revealing a circulating signature of tissue status.

ImmUniverse aims to optimise this process, evaluating frequency, intensity, exposure time, and duty cycle through systematic in vitro tests. An appropriate setup will prevent wave reflection/absorption.

Clinical studies:

1. in vitro study on ulcerative colitis (UC) patients‘ cells,
2. mice study to determine effective LIPUS parameters and effects without worsening animal disease,
3. pilot study on UC patients to validate LIPUS as a liquid biopsy reflecting tissue status, once parameters are established, and
4. clinical study on UC patients to assess disease progression monitoring using this approach.