Abstract Sensing4Health
Arjan Tibbe – IMEC-OnePlanet
11:10 – 11:40 | Room 8

Within OnePlanet we use disruptive sensor and data science driven applications to enable real-time control in the domains of health, environment, agriculture and food. In general, these sensors need to be able to measure low concentrations in complex environments and matrices.

Nanotechnology allows to produce small sensors that can be applied at locations that were not available before. A good example of this is our ingestible pill that allows to acquire health parameters inside the GI-tract at real-time while it travels through. However, nanotechnology only will not be sufficient. Realtime data acquisition requires new ways for data transfer and analysis as well as platforms to share and use this data. In addition, the complex interface between matrix and sensor surface doesn’t change by using nanotechnologies and new sensing methods are required to perform measurements inside complex environments like the GI-tract or bioreactors.

Here we present some of our latest application driven research within OnePlanet that is using combinations of different nanotechnologies.

Abstract Integrated sensing for tissue barrier integrity analysis in organ-on-chip systems
Pratik Tawade – Delft University of Technology
11:40 – 12:00 | Room 8

Pratik Tawade¹, Lovro Ivančević^1,2, Hande Aydogmus^1,3, Massimo Mastrangeli¹

¹Electronic Components, Technology and Materials, Department of Microelectronics,
²Microsoft Quantum Lab Delft, the Netherlands

³Else Kooi Laboratory, Delft University of Technology, Delft, the Netherlands

Organ-on-Chip (OoC) are in-vitro systems that recapitulate in-vivo-like tissue and organ functions to provide more realistic mimics of human physiology and disease than existing in-vitro models. OoCs can be used for drug development to assess drug effects on human tissues, in personalized medicine to determine appropriate drugs and dosages for individual patients, and disease modeling for studying mechanisms and potential therapies [1]. Monitoring the OoC microenvironment and the dynamic response of these miniaturized organs is thereby critical. Specifically, there is an increasing demand for integrated sensors capable of providing continuous, real-time in-situ measurements. Culture models of biological barriers, such as gut and blood-brain-barrier (BBB), are essential for studying pathophysiological functions, drug adsorption, and disease mechanisms [2]. Measurements of trans-epithelial electrical resistance (TEER), and impedance spectroscopy more generally, offer invaluable insight into how tissue barrier disruption causes serious ailments like inflammatory bowel disease, and multiple sclerosis. Impedance spectroscopy across a cellular monolayer quantifies the permeability and integrity of tight junctions formed by barrier cells [3]. We present the design and fabrication of a novel silicon-based OoC device for measuring the permeability of the BBB and gut tissue using impedance spectroscopy. The device incorporates a few hundred nanometer-thin, suspended silicon nitride microporous transparent membrane, providing an in-vivo-like separation distance between cells, essential for establishing realistic in-vitro gut and BBB models. The device adopts a sidewall electrode topology, offering an unobstructed view of the cell culture environment (figure below). Integrated electrodes are positioned on the short slanted sidewalls of the channel, along with optimized in-vivo-like shear stress values based on finite element analysis. Simulation-based modeling was utilized to optimize the electrode topology, demonstrating high uniformity in measurement sensitivity and eliminating the need for commonly used measurement corrections. In this work we devised a cleanroom-based reproducible, wafer-scale fabrication flow to create a two-channel microfluidic organ-on-chip device with integrated impedance spectroscopy electrodes.

1. M. Mastrangeli and J. van den Eijnden-van Raaij, Stem Cell Rep., 16, 2037–2043, (2021)
2. F. Walter, S. Valkai, A. Kincses, A. Petneházi et al., Sens. Act. B, 222, 1209-1219, (2016)
3. D. Dean, T. Ramanathan, D. Machado, R. Sundararajan, J. Electrost., 66, 165-177, (2007)

Abstract Demonstrator for cartridge based photonic biosensor development
Gerald Ebberink – Saxion
12:00 -12:20 | Room 8

Gerald Ebberink, Roy de Kinkelder, Lantian Chang, Cas Damen

Saxion University, Applied NanoTechnology

Photonic biosensors for medical diagnostics show equal or better performance in terms of sensitivity, accuracy, and reliability as compared to other techniques. The price per test for such devices is mainly determined by the costs of the (disposable) cartridge with the sensor chip and bioactive layer.

If active components can be left out of the cartridge a significant cost reduction can be obtained. This in turn brings up the challenge of coupling light from an external source to the sensor chip inside the cartridge and back towards detectors.

Here, a demonstrator system is presented, that implements an initial passive alignment step followed by an active alignment step. The initial alignment is realized by obtaining high accuracy, placing the cartridge in an acceptor slot. This results in finding a “first light” state, which allows the active alignment to take over. The active alignment is then realized by moving the fibre to the position with optimal coupling efficiency.

This demonstrator has been used for two sets of experiments. The first set comprises the comparison of the re-insertion accuracy of cartridges produced with different materials and production techniques. The second set of experiments is to test several active alignment algorithms on progressively reduced stage performance. Results from both experiments will be presented.

Abstract 3D-Folded Microneedle array for neural recording and stimulation
Peter van Delft – Philips
12:20 – 12:40 | Room 8

Peter van Delft¹, Bas Jacobs¹, Marcus Louwerse¹, Elena Beletkaia¹, Aliki Tsopela¹, Joost van Beek¹, Paul Dijkstra¹

¹Royal Philips N.V., MEMS and Microdevices, Eindhoven, the Netherlands

Microneedle arrays fabricated by microelectromechanical systems (MEMS) technology are used to detect or stimulate neural activity in for example the brain [1]. Similar probes fitted with micro-fluidic channels are applied for transdermal fluidic analysis and drug delivery [2].  Micro-needles incorporating a waveguide to optically stimulate brain tissue locally have also been demonstrated [3]. For many of these applications, the aim is to perform in-vivo high-resolution three-dimensional (3D) imaging and stimulation in deep tissue of a solid organ such as a brain. Therefore, microneedle array should be designed as to maximize number of probing locations per unit of volume while inducing minimum damage to the surrounding tissue when the probe is inserted. Furthermore, the power efficiency and signal-to-noise ratio can be improved when also electrical signal processing circuits are integrated in these probes e.g., by processing the probe monolithically on a CMOS chip or assembling a CMOS chip onto the probe.

One of the main challenges in 3D micro-needle array development is the scalability of the manufacturing process. Increasing the number and length of needles and number of electrodes per needle typically goes hand in hand with an increase in manufacturing complexity, module size, and cost. The cost is further increased when integrating the microneedle into CMOS. Here we present a process flow using the Flex to Rigid (F2R) platform, that overcomes these scalability limitations. The F2R process allows for the manufacturing of 2D and 3D arrays where the size of the array can be scaled by merely adapting the mask layout during wafer level processing. A 3×3 needle array demonstrator is realized incorporating needles (See Figure 1.) that are 5mm long, 72µm wide and 40µm thick. There are 4 electrodes per needle, making a total of 36 electrodes that can be individually addressed using an ASIC that is flip chip mounted on the back of the array. Optionally, a buried microfluidic channel can be incorporated in the needle as well.

Figure 1: The folded 3×3 Microneedle array attached to a flex foil and 2 flip chip mounted ASIC dies.

REFERENCES

[1] M.-Y. Cheng, R. B. Damalerio, W. Chen and R. Rajkumar, “Ultracompact Multielectrode Array for Neurological Monitoring,” Sensors, 2019.

[2] Xie, L.; Zeng, H.; Sun, J.; Qian, W. “Engineering Microneedles for Therapy and Diagnosis: A Survey”. Micromachines, 11, 271, 2020.

[3] H. Shin, Y. Son1, U. Chae, J. Kim, N. Choi, H. J. Lee, J. Woo, Y. Cho, S. H. Yang and C. J. L. &. I.-J. Cho, “Multifunctional multi-shank neural probe for investigating and modulating long-range neural circuits in vivo,” Nature Communications, no. 10, p. 3777, 2019