Mariana Medina-Sánchez

Cellular Cargo Delivery: Toward Assisted Fertilization by Sperm-Carrying Micromotors

We present artificially motorized sperm cells-a novel type of hybrid micromotor, where customized microhelices serve as motors for transporting sperm cells with motion deficiencies to help them carry out their natural function. Our results indicate that metal-coated polymer microhelices are suitable for this task due to potent, controllable, and nonharmful 3D motion behavior. We manage to capture, transport, and release single immotile live sperm cells in fluidic channels that allow mimicking physiological conditions. Important steps toward fertilization are addressed by employing proper means of sperm selection and oocyte culturing. Despite the fact that there still remain some challenges on the way to achieve successful fertilization with artificially motorized sperms, we believe that the potential of this novel approach toward assisted reproduction can be already put into perspective with the present work.

On-chip magneto-immunoassay for Alzheimer's biomarker electrochemical detection by using quantum dots as labels

Electrochemical detection of cadmium-selenide/zinc-sulfide (CdSe@ZnS) quantum dots (QDs) as labeling carriers in an assay for apolipoprotein E (ApoE) detection has been evaluated. The immunocomplex was performed by using tosylactivated magnetic beads as preconcentration platform into a flexible hybrid polydimethylsiloxane (PDMS)-polycarbonate (PC) microfluidic chip with integrated screen printed electrodes (SPE). All the immunoassay was performed in chip and in flow mode. The sensitive electrochemical detection was obtained by square wave anodic stripping voltammetry. ApoE was evaluated for its potential as biomarker for Alzheimers disease detection, achieving a limit of detection (LOD) of ~12.5 ng mL(-1) with a linear range from 10 to 200 ng mL(-1) and high accuracy for diluted human plasma.

High-Performance Three-Dimensional Tubular Nanomembrane Sensor for DNA Detection

We report an ultrasensitive label-free DNA biosensor with fully on-chip integrated rolled-up nanomembrane electrodes. The hybridization of complementary DNA strands (avian influenza virus subtype H1N1) is selectively detected down to attomolar concentrations, an unprecedented level for miniaturized sensors without amplification. Impedimetric DNA detection with such a rolled-up biosensor shows 4 orders of magnitude sensitivity improvement over its planar counterpart. Furthermore, it is observed that the impedance response of the proposed device is contrary to the expected behavior due to its particular geometry. To further investigate this difference, a thorough model analysis of the measured signal and the electric field calculation is performed, revealing enhanced electron hopping/tunneling along the DNA chains due to an enriched electric field inside the tube. Likewise, conformational changes of DNA might also contribute to this effect. Accordingly, these highly integrated three-dimensional sensors provide a tool to study electrical properties of DNA under versatile experimental conditions and open a new avenue for novel biosensing applications (i.e., for protein, enzyme detection, or monitoring of cell behavior under in vivo like conditions).

Spermatozoa as Functional Components of Robotic Microswimmers

In recent years, the combination of synthetic micro- and nanomaterials with spermatozoa as functional components has led to the development of tubular and helical spermbots - microrobotic devices with potential applications in the biomedical and nanotechnological field. Here, the initial advances in this field are discussed and the use of spermatozoa as functional parts in microdevices elaborated. Besides the potential uses of these hybrid robotic microswimmers, the obstacles along the way are discussed, with suggestions for solutions of the encountered challenges also given.

Water Activated Graphene Oxide Transfer Using Wax Printed Membranes for Fast Patterning of a Touch Sensitive Device

We demonstrate a graphene oxide printing technology using wax printed membranes for the fast patterning and water activation transfer using pressure based mechanisms. The wax printed membranes have 50 μm resolution, longtime stability and infinite shaping capability. The use of these membranes complemented with the vacuum filtration of graphene oxide provides the control over the thickness. Our demonstration provides a solvent free methodology for printing graphene oxide devices in all shapes and all substrates using the roll-to-roll automatized mechanism present in the wax printing machine. Graphene oxide was transferred over a wide variety of substrates as textile or PET in between others. Finally, we developed a touch switch sensing device integrated in a LED electronic circuit.

Graphene/Silicon heterojunction Schottky diode for vapors sensing using impedance spectroscopy.

A graphene(G)/Silicon(Si) heterojunction Schottky diode and a simple method that evaluates its electrical response to different chemical vapors using electrochemical impedance spectroscopy (EIS) are implemented. To study the impedance response of the device of a given vapor, relative impedance change (RIC) as a function of the frequency is evaluated. The minimum value of RIC for different vapors corresponds to different frequency values (18.7, 12.9 and 10.7 KHz for chloroform, phenol, and methanol vapors respectively). The impedance responses to phenol, beside other gases used as model analytes for different vapor concentrations are studied. The equivalent circuit of the device is obtained and simplified, using data fitting from the extracted values of resistances and capacitances. The resistance corresponding to interphase G/Si is used as a parameter to compare the performance of this device upon different phenol concentrations and a high reproducibility with a 4.4% relative standard deviation is obtained. The efficiency of the device fabrication, its selectivity, reproducibility and easy measurement mode using EIS makes the developed system an interesting alternative for gases detection for environmental monitoring and other industrial applications.

Antithyroid drug detection using an enzyme cascade blocking in a nanoparticle‐based lab‐on‐a‐chip system

A methimazole (MT) biosensor based on a nanocomposite of magnetic nanoparticles (MNPs) functionalized with iridium oxide nanoparticles (IrOx NPs) and tyrosinase (Tyr) immobilized onto screen printed electrode (SPE) by using a permanent magnet is presented. This system is evaluated in batch mode via chelating copper at the active site of tyrosinase and in flow mode by thioquinone formation. The MT detection in flow mode is achieved using a hybrid polydimethylsiloxane/polyester amperometric lab-on-a-chip (LOC) microsystem with an integrated SPE. Both systems are very sensitive with low limit of detection (LOD): 0.006 μM and 0.004 μM for batch and flow modes, respectively. Nevertheless, the flow mode has advantages such as its reusability, automation, low sample volume (6 μL), and fast response (20 s). Optimization and validation parameters such as enzyme-substrate amount, flow rate, inhibition conditions, repeatability and reproducibility of the biosensor have been performed. The proposed methods have been applied in MT detection in spiked human serum and pharmaceutical dosage forms.

Enhanced detection of quantum dots labeled protein by simultaneous bismuth electrodeposition into microfluidic channel.

In this study, we propose an electrochemical immunoassay into a disposable microfluidic platform, using quantum dots (QDs) as labels and their enhanced detection using bismuth as an alternative to mercury electrodes. CdSe@ZnS QDs were used to tag human IgG as a model protein and detected through highly sensitive stripping voltammetry of the dissolved metallic component (cadmium in our case). The modification of the screen printed carbon electrodes (SPCEs) was done by a simple electrodeposition of bismuth that was previously mixed with the sample containing QDs. A magneto‐immunosandwich assay was performed using a micromixer. A magnet placed at its outlet in order to capture the magnetic beads used as solid support for the immunoassay. SPCEs were integrated at the end of the channel as detector. Different parameters such as bismuth concentration, flow rate, and incubation times, were optimized. The LOD for HIgG in presence of bismuth was 3.5 ng/mL with a RSD of 13.2%. This LOD was about 3.3‐fold lower than the one obtained without bismuth. Furthermore, the sensitivity of the system was increased 100‐fold respect to experiments carried out with classical screen‐printed electrodes, both in presence of bismuth.

Micro- and nano-motors: the new generation of drug carriers

Micro- and nano-motors are emerging as novel drug delivery platforms, offering advantages such as rapid drug transport, high tissue penetration and motion controllability. They can be propelled and/or guided by endogenous (i.e., chemotaxis) or exogenous stimuli (e.g., ultrasound, magnetic fields, light) toward the area of interest. Moreover, such stimuli can be used to trigger the release of a therapeutic payload when the motor reaches certain location in order to improve the drug targeting. In this review article, we highlight medically oriented micro-/nano-motors, in particular the ones created for targeted drug delivery, and discuss their current limitations and possibilities toward in vivo applications.

Microsystems for Single-Cell Analysis

Due to the heterogeneity that exists even between cells of the same tissue, it is essential to use techniques and devices able to resolve the characteristics of single biological cells, such as morphology, metabolism, or response to drugs. To that end, different structures with sizes similar to that of individual cells have been developed in recent years, which allow single‐cell studies with high sensitivity and high resolution. By employing a variety of sensing strategies, one can obtain complementary information about individual cells, and thus create a complete picture of cellular properties. This review aims to provide an overview of microscale single‐cell sensors. The progress in micrometer‐sized sensing probes as well as microfluidic and micropatterned devices is described, showing the capabilities of the available systems. In addition, a comprehensive compendium of systems based on rolled‐up microtubes, which have the potential to advance and improve the single‐cell analysis microsystem field, is comprised.