Staff member

Enrique Martínez Bueno

Technical Support to Research
Synthetic, Perceptive, Emotive and Cognitive Systems (SPECS)

Staff member publications

Torras, N., García-Díaz, M., Fernández-Majada, V., Martínez, E., (2018). Mimicking epithelial tissues in three-dimensional cell culture models Frontiers in Bioengineering and Biotechnology 6, Article 197

Epithelial tissues are composed of layers of tightly connected cells shaped into complex three-dimensional (3D) structures such as cysts, tubules, or invaginations. These complex 3D structures are important for organ-specific functions and often create biochemical gradients that guide cell positioning and compartmentalization within the organ. One of the main functions of epithelia is to act as physical barriers that protect the underlying tissues from external insults. In vitro, epithelial barriers are usually mimicked by oversimplified models based on cell lines grown as monolayers on flat surfaces. While useful to answer certain questions, these models cannot fully capture the in vivo organ physiology and often yield poor predictions. In order to progress further in basic and translational research, disease modeling, drug discovery, and regenerative medicine, it is essential to advance the development of new in vitro predictive models of epithelial tissues that are capable of representing the in vivo-like structures and organ functionality more accurately. Here, we review current strategies for obtaining biomimetic systems in the form of advanced in vitro models that allow for more reliable and safer preclinical tests. The current state of the art and potential applications of self-organized cell-based systems, organ-on-a-chip devices that incorporate sensors and monitoring capabilities, as well as microfabrication techniques including bioprinting and photolithography, are discussed. These techniques could be combined to help provide highly predictive drug tests for patient-specific conditions in the near future.

Keywords: 3D cell culture models, Biofabrication, Disease modeling, Drug screening, Epithelial barriers, Microengineered tissues, Organ-on-a-chip, Organoids

de Goede, M., Chang, L., Dijkstra, M., Obregón, R., Ramón-Azcon, J., Martínez, E., Padilla, L., Adan, J., Mitjans, F., García-Blanco, S.M., (2018). Al2O3 Microresonator based passive and active biosensors ICTON 2018 20th International Conference on Transparent Optical Networks , IEEE Computer Society (Bucharest, Romania) , 8473820

Al2O3 microresonators were realized for sensing applications of both passive and active devices. Passive microring resonators exhibited quality factors up to 3.2×105 in air. A bulk refractive index sensitivity of 100 nm/RIU was demonstrated together with a limit of detection of 10-6 RIU. Functionalizing their surface allowed for the label-free detection of the biomarker rhS100A4 from urine with a limit of detection of 3 nM. Furthermore, single-mode Al2O3:Yb3+ microdisk lasers were realized that could operate in an aqueous environment. Upon varying the bulk refractive index their lasing wavelength could be tuned with a sensitivity of 20 nm/RIU and a LOD of 3×10-6 RIU.

de Goede, M., Chang, L., Dijkstra, M., Obregón, R., Ramón-Azcon, J., Martínez, E., Padilla, L., Adan, J., Mitjans, F., García-Blanco, S.M., (2018). Al2O3 Mmicroresonators for passive and active sensing applications Sensors 2018 Optical Sensors , OSA - The Optical Society (Zurich, Switzerland) Part F110, 1-2

The Al2O3 waveguide technology was explored for sensing applications. Passive microring resonators with a quality factor in air of 3.2×105 were developed with a bulk refractive index sensitivity of ~100 nm/RIU and limit of detection of ~10-6 RIU. These were functionalized to detect the biomarker rhS100A4 from urine down to concentrations of 3 nM. Furthermore, Al2O3:Yb3+ microdisk lasers were realized that exhibited single mode lasing operation in water. Their lasing wavelength was tuned by varying the bulk refractive index and a bulk refractive index sensitivity of ~20 nm/RIU with a LOD of ~3×10-6 was achieved.

de Goede, M., Dijkstra, M., Obregón, R., Martínez, E., García-Blanco, S.M., (2018). High quality factor Al2O3 microring resonators for on-chip sensing applications Proceedings SPIE. Integrated Optics: Devices, Materials, and Technologies XXII SPIE OPTO , SPIE (California, USA) 10535, 7

Microring resonators find many applications for on-chip integrated optical sensors. Their spectral response contains resonance dips that shift due to variations of the optical path length of the microring probed. Numerous examples of such microring resonator sensors in the SOI, Si3N4 and SiON waveguide technologies have been reported for the detection of bulk refractive index variations and the label-free detection of biomarkers. Al2O3 is an alternative waveguide technology that exhibits low optical propagation losses, is transparent over a large spectral range extending from the visible to the mid-IR and permits co-doping with active rare-earth ions, which enables the co-integration of active devices on the chip. In this work an Al2O3 microring resonator sensor was developed for the label-free detection of protein biomarkers. The uncladded microring with a radius of 200 μm had a measured quality factor of 3.2 × 105 at 1550 nm. Submerging the devices in water decreased the quality factor to 45 × 103. This corresponds with propagation losses in the rings of 0.6 dB/cm and 5.7 dB/cm respectively. The bulk refractive index sensitivity of the sensor was determined by flowing NaCl dissolved in water in different concentrations. A sensitivity of 102.3 ± 0.5 nm/RIU with a corresponding limit of detection of 1.6 × 10-6 RIU was demonstrated for TM polarized light. High affinity human monoclonal antibodies mAb S100A4 were immobilized on the sensor to detect the S100A4 protein biomarker down to 12 nM concentrations. These results demonstrate the feasibility of this material for label-free optical biosensors.