Xavi Illa

• Researcher at Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN)

Deep brain stimulation (DBS) is a neuroelectronic therapy for the treatment of a broad range of neurological disorders, including Parkinson’s disease. Current DBS technologies face important limitations, such as large electrode size, invasiveness, and lack of adaptive therapy based on biomarker monitoring. In this study, we investigate the potentia...

Brain states exhibit slow transitions that are coordinated by slowly varying homeostatic and neuromodulatory factors. These slow dynamics modulate neuronal excitability, giving rise to brain state-specific synchronous oscillatory patterns across brain regions, which in turn could reflect local infra-slow variations in the extracellular potential. S...

Neuroelectronic prostheses are being developed for restoring vision at the retinal level in patients who have lost their sight due to photoreceptor loss. The core component of these devices is the electrode array, which enables interfacing with retinal neurons. Generating the perception of meaningful images requires high-density microelectrode arra...

The persistence of photoresist residues from microfabrication procedures causes significant obstacles in the technological advancement of graphene-based electronic devices. These residues induce undesired chemical doping effects, diminish carrier mobility, and deteriorate the signal-to-noise ratio, making them critical in certain contexts, includin...

Conventional gut-on-chip (GOC) models typically represent the epithelial layer of the gut tissue, neglecting other important components such as the stromal compartment and the extracellular matrix (ECM) that play crucial roles in maintaining intestinal barrier integrity and function. These models often employ hard, flat porous membranes for cell cu...

Graphene-enabled micro-transistor arrays can be used to improve our understanding of how infraslow brain signals relate to changes in cerebral blood flow.

One of the critical factors determining the performance of neural interfaces is the electrode material used to establish electrical communication with the neural tissue, which needs to meet strict electrical, electrochemical, mechanical, biological and microfabrication compatibility requirements. This work presents a nanoporous graphene-based thin-...

Graphene-based solution-gated field-effect transistors (gSGFETs) allow the quantification of the brain's full-band signal. Extracellular alternating current (AC) signals include local field potentials (LFP, population activity within a reach of hundreds of micrometers), multiunit activity (MUA), and ultimately single units. Direct current (DC) pote...

Graphene solution‐gated field‐effect transistors (gSGFETs) offer high potential for chemical and biochemical sensing applications. Among the current trends to improve this technology, the functionalization processes are gaining relevance for its crucial impact on biosensing performance. Previous efforts are focused on simplifying the attachment pro...

In the last decade, solution-gated graphene field effect transistors (GFETs) showed their versatility in the development of a miniaturized multiplexed platform for electrophysiological recordings and sensing. Due to their working mechanism, the surface functionalisation and immobilisation of receptors are pivotal to ensure the proper functioning of...

Correction for 'Organ-on-a-chip with integrated semitransparent organic electrodes for barrier function monitoring' by Denise Marrero et al., Lab Chip, 2023, https://doi.org/10.1039/d2lc01097f.

Nanostructured materials provide an outstanding opportunity to both stimulate and measure cellular processes. In the context of tight junctions, it was previously reported that transient application of a nanotopographic surface over the apical brush border membrane of epithelial monolayers triggers redistribution of ZO-1, claudins, and F-actin that...

Nanostructured materials provide an outstanding opportunity to both stimulate and measure cellular processes. In the context of tight junctions, it was previously reported that transient application of a nanotopographic surface over the apical brush border membrane of epithelial monolayers triggers redistribution of ZO–1, claudins, and F–actin that...

Mapping the entire frequency bandwidth of brain electrophysiological signals is of paramount importance for understanding physiological and pathological states. The ability to record simultaneously DC-shifts, infraslow oscillations (<0.1 Hz), typical local field potentials (0.1–80 Hz) and higher frequencies (80–600 Hz) using the same recording site...

Organs-on-a-chip (OoC) are cell culture platforms that replicate key functional units of tissues in vitro. Barrier integrity and permeability evaluation are of utmost importance when studying barrier-forming tissues. Impedance spectroscopy is a powerful tool and is widely used to monitor barrier permeability and integrity in real-time. However, dat...

Electroretinography (ERG) is a clinical test employed to understand and diagnose many retinopathies. ERG is usually performed by placing a macroscopic ring gold wire electrode on the cornea while flashing light onto the eye to measure changes in the transretinal potential. However, macroscopic gold electrodes are severely limiting since they do not...

This paper presents a 1024-channel neural read-out integrated circuit (ROIC) for solution-gated GFET sensing probes in massive $\mu$ ECoG brain mapping. The proposed time-domain multiplexing of GFET-only arrays enables low-cost and scalable hybrid headstages. Low-power CMOS circuits are presented for the GFET analog frontend, including a CDS mech...

Mapping the entire frequency bandwidth of neuronal oscillations in the brain is of paramount importance for understanding physiological and pathological states. The ability to record simultaneously infraslow activity (<0.1 Hz) and higher frequencies (0.1-600 Hz) using the same recording electrode would particularly benefit epilepsy research. Howeve...

Objective. The development of experimental methodology utilizing graphene micro-transistor arrays to facilitate and advance translational research into cortical spreading depression (CSD) in the awake brain. Approach. CSDs were reliably induced in awake nontransgenic mice using optogenetic methods. High-fidelity DC-coupled electrophysiological mapp...

Objective. The development of experimental methodology utilizing graphene micro-transistor arrays to facilitate and advance translational research into cortical spreading depression (CSD) in the awake brain. Approach. CSDs were reliably induced in awake nontransgenic mice using optogenetic methods. High-fidelity DC-coupled electrophysiological mapp...

Evaluating biocompatibility is a core essential step to introducing a new material as a candidate for brain-machine interfaces. Foreign body reactions often result in glial scars that can impede the performance of the interface. Having a high conductivity and large electrochemical window, graphene is a candidate material for electrical stimulation...

Over the last few years, the intestine has been extensively studied using in vitro microfluidic systems, commonly known as gut-on-a-chip (GOC) devices. This interest has been due not only to the importance of the intestine's proper functions but also to the relationship that this organ and the microbiota that inhabits it has with the rest of the bo...

Graphene active sensors have demonstrated promising capabilities for the detection of electrophysiological signals in the brain. Their functional properties, together with their flexibility as well as their expected stability and biocompatibility have raised them as a promising building block for large-scale sensing neural interfaces. However, in o...

Low-frequency noise (LFN) variability in graphene transistors (GFETs) is for the first time researched in this work under both experimental and theoretical aspects. LFN from an adequate statistical sample of long-channel solution-gated single-layer GFETs is measured in a wide range of operating conditions while a physics-based analytical model is d...

Low-frequency noise (LFN) variability in graphene transistors (GFETs) is for the first time researched in this work. LFN from an adequate statistical sample of long-channel solution-gated single-layer GFETs is measured in a wide range of operating conditions while a physics-based analytical model is derived that accounts for the bias dependence of...

Poor metal contact interfaces are one of the main limitations preventing unhampered access to the full potential of two-dimensional materials in electronics. Here we present graphene solution-gated field-effect-transistors (gSGFETs) with strongly improved linearity, homogeneity and sensitivity for small sensor sizes, resulting from ultraviolet ozon...

Sensor arrays used to detect electrophysiological signals from the brain are of major importance in neuroscience and biomedical engineering. However, the number of sensors that can be interfaced with macroscopic data acquisition systems currently limits the bandwidth of these devices. This bottleneck originates in the fact that, typically, sensors...

Electrocorticography (ECoG) is a well-established technique to monitor electrophysiological activity from the surface of the brain and has proved crucial for the current generation of neural prostheses and brain-computer interfaces. However, existing ECoG technologies still fail to provide the resolution necessary to accurately map highly localized...

Graphene solution‐gated field‐effect transistors (g‐SGFETs) are promising sensing devices to transduce electrochemical potential signals in an electrolyte bath. However, distortion mechanisms in g‐SGFET, which can affect signals of large amplitude or high frequency, have not been evaluated. Here, a detailed characterization and modeling of the harm...

The use of graphene transistors for transducing neural activity has demonstrated the potential to extend the spatiotemporal resolution of electrophysiological methods to lower frequencies, providing a new tool to understand the role of the infra-slow activity.

A novel sensing device for simultaneous dissolved oxygen (DO) and pH monitoring specially designed for biofilm profiling is presented in this work. This device enabled the recording of instantaneous DO and pH dynamic profiles within biofilms, improving the tools available for the study and the characterization of biological systems. The microsensor...

Recording infraslow brain signals (<0.1 Hz) with microelectrodes is severely hampered by current microelectrode materials, primarily due to limitations resulting from voltage drift and high electrode impedance. Hence, most recording systems include high-pass filters that solve saturation issues but come hand in hand with loss of physiological and p...

Developing new standardized tools to characterize brain recording devices is critical to evaluate neural probes and for translation to clinical use. The signal-to-noise ratio (SNR) measurement is the gold standard for quantifying the performance of brain recording devices. Given the drawbacks with the SNR measure, our first objective was to devise...

Epithelia and endothelia delineate tissue compartments and control their environments by regulating the passage of ions and solutes. This barrier function is essential for the development and maintenance of multicellular organisms, and its dysfunction is associated with numerous human diseases. Recent advances in biomaterials and microfabrication t...

The demand for real-time monitoring of cell functions and cell conditions has dramatically increased with the emergence of Organ-On-a-Chip (OOC) systems. However, the incorporation of co-cultures and microfluidic channels in...

Brain–computer interfaces and neural prostheses based on the detection of electrocorticography (ECoG) signals are rapidly growing fields of research. Several technologies are currently competing to be the first to reach the market; however, none of them fulfill yet all the requirements of the ideal interface with neurons. Thanks to its biocompatibi...

Transepithelial electrical measurements in the renal tubule have provided a better understanding of how kidney regulates electrolyte and water homeostasis through the reabsorption of molecules and ions (e.g., H2O and NaCl). While experiments and measurement techniques using native tissue are difficult to prepare and to reproduce, cell cultures cond...

Cortical slow oscillations (SO) of neural activity spontaneously emerge and propagate during deep sleep and anesthesia and are also expressed in isolated brain slices and cortical slabs. We lack full understanding of how SO integrate the different structural levels underlying local excitability of cell assemblies and their mutual interaction. Here,...

The interconnection of different tissue-tissue interfaces may extend organ-on-chips to a new generation of sophisticated models capable of recapitulating more complex organ-level functions. Single interfaces are largely recreated in organ-on-chips by culturing the cells on opposite sides of a porous membrane that splits a chamber in two or by conne...

Biomonitoring is a research topic that has largely relied on cell culture systems. Recently, the development of “Organ-on-a-Chip” (OC) platforms and the need for a continuous monitoring of these systems has increased its interest. However, the biomonitorization in these systems is still at its infancy due to the difficulty to adapt the sensors to m...

Transepithelial electrical resistance (TEER) measurements are regularly used in in vitro models to quantitatively evaluate the cell barrier function. Although it would be expected that TEER values obtained with the same cell type and experimental setup were comparable, values reported in the literature show a large dispersion for unclear reasons. T...

A 16-electrode flexible microprobe presenting an array of holes in its sensing area has been developed using SU-8 negative photoresist as a substrate material. The design of the microprobe consisted on six groups of 2-3 electrodes (50 μm in diameter and separated by 200 μm) placed in-between the array of holes. Distances between each group were app...

In this work, we present the use of interdigitated electrodes (IDEs) for performing electrical impedance spectroscopy (EIS) measurements to monitor a microfluidic blood brain barrier model. In particular, an electrode configuration which would not impair the optical visualization of the cell culture is proposed. Numerical studies have been performe...

We describe a unique, versatile bioreactor consisting of two plates and a modified commercial porous membrane suitable for in vitro analysis of the liver sinusoid. The modular bioreactor allows i) excellent control of the cell seeding process; ii) cell culture under controlled shear stress stimulus, and; iii) individual analysis of each cell type u...

We describe a unique, versatile bioreactor consisting of two plates and a modified commercial porous membrane suitable for in vitro analysis of the liver sinusoid. The modular bioreactor allows i) excellent control of the cell seeding process; ii) cell culture under controlled shear stress stimulus, and; iii) individual analysis of each cell type u...

The cornea is a very particular tissue due to its transparency and its barrier function as it has to resist against the daily insults of the external environment. In addition, maintenance of this barrier function is of crucial importance to ensure a correct corneal homeostasis. Here, the corneal epithelial permeability has been assessed in vivo by...

Interdigitated microband electrodes are important electroanalytical tools, and have been used in the construction of advanced sensing and biosensing devices for a long time. Nanoband-based systems, on the other hand, are more difficult to come by, as their fabrication involves the use of costly and scarce e-beam lithography resources. In this work...

The selective detection of cations is commonly required in a wide range of biomedical applications. We have fabricated a low-cost flexible polyimide multi-sensor platform that integrates K + and Na + ion sensitive microelectrodes (µISE) for biomedical applications in organic media. The platform is fabricated using rapid prototyping techniques based...

A novel modular bioreactor that integrates a home-modified membrane placed between two plates is presented in order to mimic and analyze the liver sinusoid. This design allows a perfect control of the cell seeding process (as it can be performed in static conditions before assembling the different parts of the bioreactor), a cell co-culture under c...

Studies concerning the functional status of the corneal epithelium are of special interest due to its key role in preventing ocular surface disease and corneal infections. In particular, quantitative measurements of the epithelium permeability translayer electrical resistance (TER) have been proven as a sensitive in vitro test for evaluation of the...

The cornea is a transparent structure composed of three layers: the epithelium, the stroma and the endothelium. To maintain its ransparency the stroma remains in a constant state of dehydration. Consequently, any ion flow disorder through the covering layers can compromise the barrier function and, therefore the corneal homeostasis. Since ionic per...

For the electrodes that present diffusion processes, grMWNT and ppy/SWNT, the contribution to the total impedance measurement of the CPE parameter and the Zd has been separated. This is shown in Figure 7 where it can be observed that the contribution at the low frequency range of Zd is significantly higher for the ppy/SWNT coating than for the grMW...

Experimental measurements to study the retention capacity and band broadening under retentive conditions using micromachined non-porous pillar array columns fabricated in cyclo olefin polymer are presented. In particular, three columns with different depths but with the same pillar structure have been fabricated via hot embossing and pressure-assis...

In this work, we report the detection of proteins by means of simultaneous fluorescence and impedance measurements in a cyclo olefin polymer (COP) chip containing an ordered pillar array column, used for reversed-phase liquid chromatography, with integrated microband gold electrodes at the end of the channel.

An experimental study of a micromachined non-porous pillar array column performance under non-retentive conditions is presented. The same pillar structure has been fabricated in cyclo-olefin polymer (COP) chips with three different depths via hot embossing and pressure-assisted thermal bonding. The influence of the depth on the band broadening alon...

This paper presents an entirely polymeric microfluidic system, made of cyclo olefin polymer (COP), with integrated gold microband electrodes for electrochemical applications in organic media. In the present work, we take advantage of the COP's high chemical stability to polar organic solvents in two different ways: (i) to fabricate gold microelectr...

Mesoporous silica with KIT-6 structure was investigated as a preconcentrating material in chromatographic systems for ammonia and trimethylamine. Its adsorption capacity was compared to that of existing commercial materials, showing its increased adsorption power. In addition, KIT-6 mesoporous silica efficiently adsorbs both gases, while none of th...

The current paper describes the development and characterization of a pillar array chip that is constructed out of a sandwich of cyclo olefin polymer (COP) sheets. The silicon master of a 5 cm long pillar array was embossed into the COP, yielding 4.3 microm deep pillars of 15.3 microm diameter with an external porosity of 43 % and a well designed s...

Low power micromachined gas sensors based on suspended micro-hotplates are presented in this work. The sensors were fabricated using Porous Silicon Technology. Two different metal-modified nanostructured sensitive materials were deposited on top of the active area of the micro-hotplates, using the micro-dropping technique: SnO2:Pd and WO3:Cr. For t...

The development of an integrated gas chromatographic system using micro and nanotechnologies is presented in this paper. For this purpose, the different components of the chromatographic system, namely the preconcentrator, the chromatographic column and the gas sensors are being investigated and developed, and the actual state of this investigation...

WO3-Cr, SnO2-Pd and TiO2-Cr nanoparticles have been prepared following a sol-gel route. The additive-modified nanostructured metal oxides have been deposited on hotplate platforms by microdropping. Functional gas test of the sensitive layers to ammonia has been performed in stationary and pulsed mode of operation. The pulsed mode fastened the regen...