Inkjet printing arrays and their applications for drug screening

Chromium inhibition and size-selected Au nanocluster catalysis for the solution growth of low-density ZnO nanowires.

The wet chemical synthesis of nanostructures has many crucial advantages over high-temperature methods, including simplicity, low-cost, and deposition on almost arbitrary substrates. Nevertheless, the density-controlled solution growth of nanowires still remains a challenge, especially at the low densities (e.g. 1 to 10 nanowires/100 μm(2)) required, as an example, for intracellular analyses. Here, we demonstrate the solution-growth of ZnO nanowires using a thin chromium film as a nucleation inhibitor and Au size-selected nanoclusters (SSNCs) as catalytic particles for which the density and, in contrast with previous reports, size can be accurately controlled. Our results also provide evide…

Luminometric Sub-nanoliter Droplet-to-droplet Arrays (LUMDA-chip) for Drug Screening on Phase I Metabolism Enzymes

Here we show the fabrication of the Luminometric Sub-nanoliter Droplet-to-droplet Array (LUMDA chip) by inkjet printing. The chip is easy to be implemented and allows for amultiplexed multi-step biochemical assay in sub-nanoliter liquid spots. This concept is here applied to the integral membrane enzyme CYP3A4, i.e. themost relevant enzymatic target for phase I drug metabolism, and to some structurally-related inhibitors.

Role of vertical ZnO nanowires on modulating the myogenic differentiation of primary mesongioblast cells

Advanced Drug Screening platforms by Inkjet printing

In this work, we show a low-cost, speed, microarray-based drug screening platform that employs inkjet printing drug dispensing on an enzymatic-rich surface. Mixtures of a model substrate (Dglucose)/ inhibitor (D-glucal) couple have been inkjet printed on a target enzymatic monolayer (glucose oxidase) linked to a functionalized silicon oxide solid surface [1]. It has been possible to fabricate microarrays with quality factors as high as those of conventional pin printing spotting. By a simple horseradish-based colorimetric enzymatic assay, the detection of biological activity at the single spot has been proved. The figure shows a scheme of the platform: molecular inks of the enzymatic substr…

Multiplexed Sub-Cellular Scale Microarrays from direct DNA Nanolithography

The multiplexed, high-throughput fabrication of microarrays is of vital importance for many applications in life sciences, including drug screening, medical diagnostics and cell biology. In single cell investigations, features smaller than 10 μm are needed for functional manipulation of sub-cellular structures. Several top-down methodologies like electron beam lithography and microcontact printing can be employed for indirect surface patterning at this scale, however those approaches often require clean rooms and multiplexing of several different biomolecules on the same surface is limited [1]. To overcome these obstacles, we combined Dip-pen nanolithography (DPN) and DNA-directed immobiliz…

Towards bioarrays of cellular-like compartments for monitoring few molecular binding events

The aim of this work is to artificially reproduce scalable cellular-like compartments on a chip, thus realizing specialized small volume systems to study the behaviour of interacting biomolecules by few binding events. In particular, we show an unprecedented solution-based protein-binding assay based on arrays of oil-confined water droplets containing protein targets, labelled ligands and other compounds.

High-throughput screening at the picoliter scale by combining Dip Pen Lithography with Inkjet printing

Drug screening is a complex, expensive and time consuming field consisting of diseasebased target identification in conjunction with high-throughput screening of chemical and natural product libraries. Conventional drug screening technology is usually time and reagent consuming (micro-, nanoliter scale) and is based on complex liquid handling robotics. In this work, we show a low-cost and miniaturized drug screening methodology based on direct bio-printing methodologies like Inkjet Printing and Dip Pen Lithography. We show the possibility to precisely deliver femtoliter scale droplets of protein targets by Dip Pen Lithography by finely tuning deposition parameters. This allows obtaining mic…

Solution processed micro- and nano-arrays for multiplexed biosensing

Ink-Jet Printing for drug srreening on microarrays: from covalent approaches to in-liquid-droplets assays

Drug screening is the complex process of retrieving chemical compounds able to modulate the activity of biological targets which are of interest for certain diseases. Conventional miniaturized drug screening technologies are based on robotic dispensers coupled with microwell arrays. However these devices require time and reagent consuming (micro-, nanoliter scale) instrumental tools, liquid handling robotics and complex detectors. Here we show a low-cost and efficient drug screening methodology based on inkjet printing for delivering molecular systems in picoliter volumes coupled with easily-implemented detection tools for probing target-drug interaction. We firstly show up a screening plat…

Patterns of glucose oxidase by inkjet printing for biosensing applications,

Droplet-to-droplet microarray for drug screening in picoliter scale

High-throughput drug screening by Printing Biology

Printing biology is our way to define a novel field employing material printing techniques generally used in plastic electronics to solve important issues of biology by miniaturized and high-throughput platforms. In this field, we already showed the possibility to use Dip Pen Lithography to fabricate single-cell biochips [1]. Also,we employed non-contact patterning methods such as inkjet printing methods to fabricate microarrays for drug screening at solid-liquid interfaces [2] or in picoliter-scale liquid droplets [3] so enabling high-throughput screening of chemical libraries onto disease-based targets. In this regard, printing methods would greatly reduce times and costs of standard drug…

Protein Arrays for Sensing Applications: Relationship beetween Printing Conditions and Pattern Properties

Synthesis, chemical characterization, computational studies and biological activity of organotin(IV) compounds interacting with enzymes involoved in epigenetic regulation. New and potential methodologies for studying molecular interactions

Our studies deal with the synthesis, the chemical characterization of organotin(IV) complexes of molecules, as caffeic acid, interacting with enzymes involved in epigenetic regulation.

ZnO Nanowires catalytic solution growth for piezotronic and bio-applications

Microarray Funzionali attraverso metodologie da Inkjet Printing: dalla biosensoristica allo screening farmacologico

Dip Pen Lithography of oligonucleotides on flexible substrates for point-of-care malaria disease testing

The first step for prevention and treatment of diseases is the accurate diagnosis. However, proper diagnostic technologies are not available in developing countries due to the lack of reliable electrical power, refrigeration and trained personnel. For this reason, there is an urgent need of low cost, rapid assays not requiring any external support. By coupling such technologies to communication infrastructures, healthcare in areas without access to medical personnel would be possible. “Paper” like substrates are ideal for fabricating such devices since they are cheap, easy to degradate after use and compatible with most of existing printing technologies [1]. We had previously shown the poss…

Nano-structured molecular thin films for bio-sensing and plastic-electronics with improved efficiency/cost ratio

Micro and Nano patterns for Biosensing: from enzymatic assays to single cells interaction arrays

In this thesis work, solution dispensing techniques have been employed for the realization of complex biological arrays. Inkjet printing techniques were employed for the generation of drug screening platforms. This approach was initially proved with a model enzyme system like Glucose Oxidase substrate covalently linked to a functionalized silicon oxide support. On this support an enzymatic substrate (D-glucose)/inhibitor (D-glucal) couple was accurately dispensed. A simple optical detection method was used to prove the screening capability of the microarray with the possibility to assay with high reproducibility at the single spot level. Afterwards, this methodology has been extended to CYP…

PRINTING NANOBIOLOGY IN AQUEOUS SYSTEMS

Our studies in the field of printing nanobiology in aqueous solution are proposed to highlight the role of water in the processes of interaction between biomolecules in drug- screening devices fabricated by bioprinting technologies and to emphasize the influence of water evaporation on the diffusion of molecules in droplets of picoliter-scale.

Drug Screening by Inkjet Printing Microarrays