Sensorised organ-on-a-chip systems

 

In life science and pharmaceutical industries, organ-on-a-chip applications are one of the fastest growing research areas. The convergence of labs-on-chips (LOCs) and cell biology has created a platform for this new method of studying human physiology. Organ-on-a-chip devices consist of microfluidic systems designed to mimic a biological entity in an artificial environment. The cell culture chips simulate the physiological response of organs.

In-vivo complexity in in-vitro devices

Micronit Microtechnologies aims to capture in-vivo complexity in simple in-vitro devices, thereby offering scientists the use of the latest technological advancements in their field of research. Micronit’s devices are already in use at several research laboratories around the world, proving their suitability in creating artificial models (including the gut and lung) in the field.

Cell culture platform

The heart of the organ-on-a-chip device is a porous membrane that is directly accessible by, for example, pipetting, making the transfer of the standard biological protocols easy. By assembling the membrane layer with a top and bottom layer and securing it with a dedicated, customisable clamp, a cell culture platform is created with separately controllable fluid-flows above and below. The resealable nature of the device allows to re-open the chips at any time, efficiently recovering the cells and making the imaging easier. Thus, a type of artificial organ is reproduced in a controllable system, where biologically relevant parameters can be measured.

Sensor integration

Easy monitoring of the biological content is still a challenge, though. To overcome this, the newest development is to integrate sensors into the organ-on-a-chip devices. Particular interest has been paid to the optical sensing of oxygen. Oxygen plays a significant role in cell biology, as it is the central substrate of the aerobic metabolism and therefore regulates the energy available to the cells. Being able to monitor the concentration of oxygen not only helps to ensure that stability in oxygen levels is maintained, but also measures the cell metabolism (how much oxygen is consumed) in real time. Additionally, it creates the possibility to mimic certain pathological conditions (such as ischaemia) or to replicate niches with low oxygen levels, for example the section of the gut that is normally inhabited by anaerobic bacteria.

Optical monitoring

In achieving this sensor-integration, Micronit has partnered with the German company PreSens, expert in contactless sensing and visualising of chemicals in solutions. This partnership has resulted in an organ-on-a-chip device with integrated oxygen sensing elements that are aligned to fibres that optically reflect results. This way, continuous monitoring of the oxygen available to the cultured cells is possible without being in physical contact with the medium. Thus, minimising the risk of compromising the fluidic integrity and sterility of the chip.

This organ-on-a-chip platform is equipped with optical sensing. The cell culturing device, which is visible inside the clamping system, has integrated sensing elements (red dots).

Future expectations

What are future expectations in the development of organ-on-a-chip devices? The progress in this field will increase the reliability, and therefore the predictivity, of the in vitro tests, reducing (and hopefully abolishing) the need for tests on animals and humans. In the early phase of the development of pharmaceuticals and cosmetics, animal models often are the only way of obtaining in vivo data that will predict human physiological responses. In this process however, animals are often subjected to invasive interventions that simulate human injuries and pathological conditions, and therefore ethically questionable. Later on in the development process, clinical trials with human participants are used. These lengthy, expensive and controversial experiments could become obsolete through the further development of organ-on-a-chip devices. This could entirely reform and improve this field of biological and chemical research.

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