M. Matteucci

Sharp beveled tip hollow microneedle arrays fabricated by LIGA and 3D soft lithography with polyvinyl alcohol

This paper describes a fabrication process of hollow microneedle arrays with a sharp beveled tip for transdermal drug delivery. A master is fabricated through a double deep x-ray lithography process. First, a polymethylmethacrylate (PMMA) sheet is exposed to produce single PMMA parts with a sawtooth profile. The tip angle of each tooth determines the final tip angle of the microneedles. The PMMA parts are assembled and glued on a conductive substrate and then exposed through a second x-ray mask containing an array of hollow triangles as absorbing structures. A metal layer is then electrodeposited around the needles in order to form the future base of the array. A polyvinyl alcohol (PVA) solution is cast on top of the master to form a negative mold of the microneedle array after a low temperature curing and peel-off steps. A liquid PMMA solution is cast on top of the PVA negative mold and after the full PMMA polymerization the PVA is dissolved in water. This fabrication method can be performed in a non-clean room environment and requires little instrumentation. It is therefore compatible with a low-cost mass-fabrication scheme.

Focusing X-rays with simple arrays of prism-like structures.

This report discusses the optimization strategy, the theoretical background and first experimental data of a new refractive lens for focusing X-rays. In order to reduce the absorption of X-rays in this transmission lens, optically passive material was removed from the necessarily concave lens shape in a highly regular pattern. The feature dimensions require lens production and replication by deep X-ray lithography, which allows shaping in only one dimension. Consequently such a lens can focus in one direction only, so a crossed lens pair is needed for two-dimensional focusing. The single lens is composed of two large prisms of millimetre size, which touch each other at one of the tips, like an old sand clock. Each large prism contains a highly regular structure of essentially identical prism-like smaller segments. The first lens prototypes focused an X-ray beam with a vertical size of 500 microm and a photon energy of 8 keV to a line with a width of only 2.8 microm. This is only slightly worse than the line width of 1.73 microm expected for its focal length of f = 2.18 m. The photon density enhancement in the focus was 25, but could have been larger as the lens can intercept a beam height of 2.6 mm.

On the feasibility of large-aperture Fresnel lenses for the microfocusing of hard X-rays

Like visible light, X-rays can also be focused by refraction in transmission lenses. For visible light this requires convex lenses while for X-rays one needs to use concave lenses instead. Both lens types can be lightened by the material removal strategy introduced by Fresnel, which results in a lens subdivided into zones. Until now, for the focusing of X-rays, stacks of standard lenses and of Fresnel lenses have mostly been produced. The first are dubbed compound refractive lenses, abbreviated as CRL. State-of-the-art systems of this kind now achieve almost theoretical performance for the focus size and the transmission. On the other hand, the latter Fresnel systems, which promise to provide larger apertures, are still in their infancy. This report discusses systematically the properties of two possible schemes for their realisation. It then compares the optimized apertures of these two schemes with those for CRLs. The best Fresnel lenses in this study are found to provide experimentally more than 50% of the expected refraction efficiency at 8.5 keV photon energy. The photon flux in their focus is then almost identical to that of perfect Be CRLs with the same focal length. This report will also interpret experimental data reported previously for other Fresnel lenses.

Fabrication of 3D micro and nanostructures for MEMS and MOEMS: an approach based on combined lithographies.

X-ray lithography is an established technique for the micro fabrication of MEMS and MOEMS well known for low sidewall surface roughness, submicron critical dimension, and high aspect ratio. Recently the typical characteristics of this technique has been developed approaching new opportunities deriving by the possibility to perform tilted exposure and by the combined use with electron beam lithography that allow to shape with direct patterning already the final material in 3D micro and nanostructures. The general approach is to concentrate the complexity of the multi layer fabrication process required to obtain 3D nanostructures mostly on the lithographic process. This capability represent a micro- and nanofabrication tool enabling new technologies. In this paper will be shown a multiple-tilted X-ray lithography procedure combined with e-beam lithography to create sub-micrometric patterns of arbitrary shape buried in 3D structure. The use of deep x-ray lithography in multi exposure configuration has been also exploited for the production of biodegradable 3D scaffold structures and of micro needles based transdermal delivery tools fabrication.

Micropatterned non-invasive dry electrodes for Brain-Computer Interface

Partially or completely paralyzed patients can benefit from advanced neuro-prostheses in which a continuous recording of electroencephalogram (EEG) is required, operating some processing and classification to control a computer (BCI, brain-computer interfaces). Patients are so allowed to control external devices or to communicate simple messages through the computer, just concentrating their attention on codified movements or on a letter or icon on a digital keyboard. Conventional electrodes usually require skin preparation and application of electrolytic gel for high quality low amplitude biopotentials recordings and are not suitable for being easily used by patient or caregivers at home in BCI or equivalent systems. In this report we describe the fabrication and characterization of dry (gel not required), non-invasive, user-friendly biopotential electrodes. The electrodes consist of a bidimensional array of micro-needles designed to pierce the first dielectric skin layer (stratum corneum) and establishing a direct contact with the living and electrical conducting cells in the epidermis (no blood vessels and nerve terminations). The easy and immediate application of the spiked electrodes makes them also attractive for every surface long-term biosignal measurements, even at patients home (EEG, electrocardiogram, etc).

On the use of clessidra prism arrays in long-focal-length X-ray focusing

Clessidra (hour-glass) X-ray lenses have an overall shape of an old hour glass, in which two opposing larger triangular prisms are formed of smaller identical prisms or prism-like objects. In these lenses, absorbing and otherwise optically inactive material was removed with a material-removal strategy similar to that used by Fresnel in the lighthouse lens construction. It is verified that when the single prism rows are incoherently illuminated they can be operated as independent micro-lenses with coinciding image positions for efficient X-ray beam concentration. Experimental data for the line width and the refraction efficiency in one-dimensional focusing are consistent with the expectations. Imperfections in the structures produced by state-of-the-art deep X-ray lithography directed only 35% of the incident intensity away from the image and widened it by just 10% to 125 microm. An array of micro-lenses with easily feasible prism sizes is proposed as an efficient retrofit for the refocusing optics in an existing beamline, where it would provide seven-fold flux enhancement.

The role of spatial coherence, diffraction and refraction in the focusing of x-rays with prism arrays of the Clessidra type

Small triangular prisms are arranged very regularly in Clessidra type x-ray lenses: they are interconnected at their tips and form a larger prism of equal shape very similarly to a stylised Christmas tree. Two opposing prisms of this type then form the Clessidra prism array. The name arrives from the similarity with an old hourglass, Clessidra in Italian. The construction principle makes the lens highly periodic in the vertical direction perpendicular to the incident beam. Thus with sufficiently spatially coherent x-ray illumination, the structure can be looked at as a linear transmission grating, i.e. a diffracting object. It is a special feature of the Clessidra lenses, that they have inherent focusing capabilities in the near field, or Fresnel regime of diffraction. In this regime the structure periodicity of the diffracting object is reproduced with different linear magnifications at the Talbot distances. The refraction in the prism structure then directs all incident intensities to a common crossover point at one of the Talbot distances. This situation was studied rigorously from the theoretical point of view. This report then presents simple models, which are in agreement with the rigorous calculations, and which can consistently explain our experimental data. For a given lens we varied the photon energy of the incident radiation and the distance between the lens and a CCD detector. In addition we moved a small slit of varying opening through the lens aperture. The experimental data will be interpreted also depending on the spatially coherently illuminated area at the lens.

Diffraction of partially coherent X-rays in clessidra prism arrays.

When small triangular prisms are arranged in arrays which have an overall appearance like an hourglass (in Italian: clessidra) they can focus X-rays owing to a combined action of diffraction and refraction. From the optical point of view these objects can be regarded as a Fresnel variant of concave transmission lenses. Consequently they can provide larger apertures than purely refractive lenses. However, one has to recognize that clessidra lenses will strongly diffract as the lens structure is periodic in the direction perpendicular to the incident beam. In experiments the diffraction is reduced because it is difficult to illuminate the large apertures with a full spatially coherent wavefront. So the illumination is at best partially coherent. In order to interpret available experimental data for this condition, diffraction theory has been applied appropriately to the clessidra structure, taking into account the limited spatial coherence. The agreement between the theoretical simulations and experimental data is very good, keeping the lens properties at their projected values and allowing for only two free model parameters. The first is the lateral spatial coherence; the second is a lens defect, a rounding of all edges and tips in the structure. Both values obtained from the simulations have been found to be in agreement with expectations.

A Transdermal Drug Delivery System Based on LIGA Technology and Soft Lithography

This report presents a transdermal drug delivery system based on LIGA fabricated microparts. It is a portable device combining a magnetically actuated micro gear pump with a microneedle array. The fluidic behaviour of the system is analyzed in order to predict its performance according to the dimension of the microparts and then compared to experimental data. The manufacturing process of both micropump and microneedle array are described.

CLESSIDRA: Focusing Hard X‐Rays Efficiently with Arrays Composed of Small Prisms

Small prisms arranged such that the number of prisms to traverse by an x‐ray beam is linearly increasing with distance from the symmetry axis of the device will direct an incident wave to a common cross over point. This structure can be understood as a special form of the Fresnel version of a concave refractive x‐ray lens. Indeed it is obtained by removing blocks of optically passive material of equal height from the concave lens shape. It will be shown that the structure has a high refraction efficiency and that the losses are produced by problems in the fabrication of sufficiently sharp tips for the prisms.