T. Mitrelias

An integrated microfluidic cell for detection, manipulation, and sorting of single micron-sized magnetic beads

A lab-on-a-chip integrated microfluidic cell has been developed for magnetic biosensing, which is comprised of anisotropic magnetoresistance (AMR) sensors optimized for the detection of single magnetic beads and electrodes to manipulate and sort the beads, integrated into a microfluidic channel. The device is designed to read out the real-time signal from 9μm diameter magnetic beads moving over AMR sensors patterned into 18×4.5μm rectangles and 10μm diameter rings and arranged in Wheatstone bridges. The beads are moved over the sensors along a 75×75μm wide channel patterned in SU8. Beads of different magnetic moments can be sorted through a magnetostatic sorting gate into different branches of the microfluidic channel using a magnetic field gradient applied by lithographically defined 120nm thick Cu striplines carrying 0.2A current.

Magnetic properties and antitumor effect of nanocomplexes of iron oxide and doxorubicin

We present a technology and magneto-mechanical milling chamber for the magneto-mechano-chemical synthesis (MMCS) of magneto-sensitive complex nanoparticles (MNC) comprising nanoparticles Fe3O4 and anticancer drug doxorubicin (DOXO). Magnetic properties of MNC were studied with vibrating magnetometer and electron paramagnetic resonance. Under the influence of mechano-chemical and MMCS, the complex show a hysteresis curve, which is typical for soft ferromagnetic materials. We also demonstrate that Lewis lung carcinoma had a hysteresis loop typical for a weak soft ferromagnet in contrast to surrounding tissues, which were diamagnetic. Combined action of constant magnetic field and radio frequency moderate inductive hyperthermia (RFH) below 40°C and MNC was found to induce greater antitumor and antimetastatic effects as compared to conventional DOXO. Radiospectroscopy shows minimal activity of FeS-protein electron transport chain of mitochondria, and an increase in the content of non-heme iron complexes with nitric oxide in the tumor tissues under the influence of RFH and MNC.

Controlled electroplating and electromigration in nickel electrodes for nanogap formation

We report the fabrication of nickel nanospaced electrodes by electroplating and electromigration for nanoelectronic devices. Using a conventional electrochemical cell, nanogaps can be obtained by controlling the plating time alone and after a careful optimization of electrodeposition parameters such as electrolyte bath, applied potential, cleaning, etc. During the process, the gap width decreases exponentially with time until the electrode gaps are completely bridged. Once the bridge is formed, the ex situ electromigration technique can reopen the nanogap. When the gap is ∼ 1 nm, tunneling current-voltage characterization shows asymmetry which can be corrected by an external magnetic field. This suggests that charge transfer in the nickel electrodes depends on the orientation of magnetic moments.

Magnetic Properties of the Superconductor LaCaBaCu3O7~!2010-02-11~!2010-04-01~!2010-06-29~!

LaCaBaCu 3 O 7 (La1113) is a superconductor below T C(onset) =80K and its structure is similar to the tetragonal YBCO. In this work the magnetic properties of a bulk La1113 sample are reported and compared to those of YBCO superconductor. We explore a possibly relation of this property to its particular crystalline structure, particularly to the oxygen deficiency. In contrast to a bulk YBCO, some magnetic characteristics of La1113 below T C are: the magnetic flux can penetrate easily the bulk in its vortex region (H C1 <H<H C2 ), fewer fields can be trapped than in YBCO, small currents are able to flow in the bulk and possible applications of La1113 are restricted under applied fields lower than 10KOe and in the range of 41K-76K. The critical current density is determined by currents flowing through grain boundaries. Peak effect is observed and it is probably caused by secondary phases or from clusters of oxygen vacancies acting as field induced pins. A first magnetic phase diagram for La1113 showing the irreversibility line is reported here. Finally, we found that the specific heat capacity of La1113 is 37.2mJ/K 2 mol.

High Throughput Biological Analysis Using Multi‐bit Magnetic Digital Planar Tags

We report a new magnetic labelling technology for high‐throughput biomolecular identification and DNA sequencing. Planar multi‐bit magnetic tags have been designed and fabricated, which comprise a magnetic barcode formed by an ensemble of micron‐sized thin film Ni80Fe20 bars encapsulated in SU8. We show that by using a globally applied magnetic field and magneto‐optical Kerr microscopy the magnetic elements in the multi‐bit magnetic tags can be addressed individually and encoded/decoded remotely. The critical steps needed to show the feasibility of this technology are demonstrated, including fabrication, flow transport, remote writing and reading, and successful functionalization of the tags as verified by fluorescence detection. This approach is ideal for encoding information on tags in microfluidic flow or suspension, for such applications as labelling of chemical precursors during drug synthesis and combinatorial library‐based high‐throughput multiplexed bioassays.

Design and fabrication of SU8 encapsulated digital magnetic carriers for high throughput biological assays

A design of a biological molecule carrier is presented for the application of high throughput multiplexing biological assays. This carrier contains a bit addressable “magnetic barcode” made of either Permalloy or cobalt thin films, sandwiched between two planar SU8 protective layers. We describe how the design of the magnetic carriers is optimized by engineering the coercivity of each barcode element, allowing the number of available signatures to be increased. Fully encapsulated digital magnetic carriers which carry a 5 bit addressable barcode were also fabricated and are presented. Writing and reading of digital carriers were both performed after releasing in dried solution.

Attaching Thiolated Superconductor Grains on Gold Surfaces for Nanoelectronics Applications

We report that the high critical temperature superconductor (HTCS) LaCaBaCu3O7 in the form of nanograins can be linked to Au(111) surfaces through self assembled monolayers (SAMs) of HS–C8H16–HS [octane (di)thiol]. We show that La1113 particles (100 nm mean diameter) can be functionalized by octane (di)thiol without affecting their superconducting critical temperature (TC=80 K). X-ray photoemission spectroscopy (XPS) analysis reveals that the thiol functional heads link the superconducting grain surfaces creating sulfonates and we deduce that bonding between the S atoms and Cu(1) atoms of the La1113 structure would be formed. We suggest a design for a superconducting transistor fabricated by immobilized La1113 nanograins in between two gold electrodes which could be controlled by an external magnetic field gate.

A composite element bit design for magnetically encoded microcarriers for future combinatorial chemistry applications

We present a new composite element (CE) bit design for the magnetic bit encoding of suspended microcarriers, which has significant implications for library generation applications based on microfluidic combinatorial chemistry. The CE bit design consists of high aspect ratio strips with appropriate dipolar interactions that enable a large coercivity range and the formation of up to 14 individually addressable bits (16 384 codes) with high encoding reliability. We investigate Ni80Fe20 and Co CEs, which produce coercivity ranges of 8–290 Oe and 75–172 Oe, respectively, showing significant improvements to previously proposed bit designs. By maintaining the total magnetic volume for each CE bit, the barcode design enables a consistent stray field for in-flow magnetic read-out. The CE bit design is characterised using magneto-optic Kerr effect (MOKE) measurements and the reliability of the design is demonstrated in a multi-bit encoding process capable of identifying each bit transition for every applied magnetic field pulse. By constraining each magnetic bit to have a unique switching field using the CE design, we enable sequential encoding of the barcode using external magnetic field pulses. We therefore discuss how the new CE barcode design makes magnetically encoded microcarriers more relevant for rapid and non-invasive detection, identification and sorting of compounds in biomolecular libraries, where each microcarrier is for example capable of recording its reaction history in daisy-chained microfluidic split-and-mix processes.

Magnetically labelled gold and epoxy bi-functional microcarriers for suspension based bioassay technologies.

Microarrays and suspension-based assay technologies have attracted significant interest over the past decade with applications ranging from medical diagnostics to high throughput molecular biology. The throughput and sensitivity of a microarray will always be limited by the array density and slow reaction kinetics. Suspension (or bead) based technologies offer a conceptually different approach, improving detection by substituting a fixed plane of operation with many individually distinguishable microcarriers. In addition to all the features of a suspension based assay technology, our technology offers a rewritable label. This has the potential to be truly revolutionary by opening up the possibility of generating, on chip, extensive labelled molecular libraries. We unveil our latest SU-8 microcarrier design with embedded magnetic films that can be utilized for both magnetic and optical labelling. The novel design significantly simplifies fabrication and additionally incorporates a gold cap to provide a dual surface, bi-functional architecture. The microcarriers are fabricated using deep-ultraviolet lithography techniques and metallic thin film growth by evaporation. The bi-functional properties of the microcarriers will allow us to use each microcarrier as its own positive control thereby increasing the reliability of our technology. Here we present details of the design, fabrication, magnetic detection and functionalization of these microcarriers.

Enabling suspension-based biochemical assays with digital magnetic microtags

Microarrays and suspension-based technologies have attracted significant interest over the past decade with applications in medical diagnostics and biochemical multiplexed assays. However, the throughput of microarrays will always be limited by the array density and the slow kinetics, while the suspension (or bead)-based technologies are currently limited by the number of distinct codes the beads can carry. A novel digital magnetic tagging technology based on magnetic tags that can be used as encoded microcarriers for biomolecular probes, is presented here. The highly disruptive platform technology can provide a very large number of unique codes, enabling a high degree of multiplexing. The design principles of a novel magnetic laboratory-on-a-chip device comprising microfluidic channels with embedded magnetic tunneling magnetoresistive sensors are also discussed.