WO2011073442A1 - Encoded fibres - Google Patents

Encoded fibres Download PDF

Info

Publication number
WO2011073442A1
WO2011073442A1 PCT/EP2010/070172 EP2010070172W WO2011073442A1 WO 2011073442 A1 WO2011073442 A1 WO 2011073442A1 EP 2010070172 W EP2010070172 W EP 2010070172W WO 2011073442 A1 WO2011073442 A1 WO 2011073442A1
Authority
WO
WIPO (PCT)
Prior art keywords
fibres
encoded
fibre
fluorophore
nanofibre
Prior art date
Application number
PCT/EP2010/070172
Other languages
French (fr)
Inventor
Chaobo Huang
Bart Lucas
Stefaan De Smedt
Joseph Demeester
Original Assignee
Universiteit Gent
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Universiteit Gent filed Critical Universiteit Gent
Publication of WO2011073442A1 publication Critical patent/WO2011073442A1/en

Links

Classifications

    • D—TEXTILES; PAPER
    • D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01D—MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
    • D01D5/00—Formation of filaments, threads, or the like
    • D01D5/0007—Electro-spinning
    • D—TEXTILES; PAPER
    • D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
    • D01F1/00—General methods for the manufacture of artificial filaments or the like
    • D01F1/02—Addition of substances to the spinning solution or to the melt
    • D01F1/06—Dyes
    • D—TEXTILES; PAPER
    • D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
    • D01F1/00—General methods for the manufacture of artificial filaments or the like
    • D01F1/02—Addition of substances to the spinning solution or to the melt
    • D01F1/10—Other agents for modifying properties
    • G—PHYSICS
    • G06—COMPUTING; CALCULATING OR COUNTING
    • G06K—GRAPHICAL DATA READING; PRESENTATION OF DATA; RECORD CARRIERS; HANDLING RECORD CARRIERS
    • G06K19/00—Record carriers for use with machines and with at least a part designed to carry digital markings
    • G06K19/06—Record carriers for use with machines and with at least a part designed to carry digital markings characterised by the kind of the digital marking, e.g. shape, nature, code
    • G06K19/06009—Record carriers for use with machines and with at least a part designed to carry digital markings characterised by the kind of the digital marking, e.g. shape, nature, code with optically detectable marking
    • G06K19/06046—Constructional details

Definitions

  • the present invention relates to the field of encoding of objects. More particularly, the present invention relates to a method and system for encoding fibres, e.g. for use in counteracting counterfeiting, as well as to fibres thus obtained or objects comprising such fibres.
  • Tablets are the most widely used drug dosage form in the world.
  • digitally encoded polystyrene micro-particles named 'memobeads'
  • information is written in the middle plane of fluorescently dyed microspheres by 'spatial selective photobleaching' of the fluorescence by the use of a confocal laser scanning microscope.
  • 'On-tablet laser NanoEncryption' was also announced, to write digital codes on the surface of tablets.
  • FIG. 1(A) a confocal image of the middle plane of a memobead is shown in FIG. 1(A).
  • the code 10 is written by "spatial selective photobleaching" of the fluorescence in dyed polystyrene microspheres. Regions at a certain depth in the microspheres are bleached by the use of a confocal laser scanning microscope. Because the fluorescent dye molecules are immobilized in the polystyrene matrix, the bleached dye molecules stay in place which prevents the code from fading away over time.
  • FIG. 1(B) the surface of memobeads is highly functionalized and contains ferromagnetic Cr02 nanoparticles 20 embedded in a coating of polyelectrolytes 30. The ferromagnetic properties of the coating allow orienting the beads correctly in a magnetic field which is necessary to make the code readable by a confocal fluorescence microscope.
  • encoded objects can be obtained which are safe for use in food or drugs.
  • the encoded fibres may for example be used in drugs in order to encode the drugs and prevent counterfeiting.
  • the encoding also can be applied to food and drugs as the fibres can be made of materials approved for use in food and/or drugs. It is an advantage of embodiments according to the present invention that such particles can easily be introduced on the item to be protected and is not restricted to introduction on the package or to direct introduction of a code on the product itself.
  • encoding can be provided on nano-fibres or more particular short portions thereof, resulting, optionally using a suitable background, in the nano-fibres being not easily visible with the naked eye.
  • the latter may not only improve applications for counterfeiting, but it also may reduce any disturbing effects for consumers of products encoded, e.g. to avoid counterfeiting.
  • fibres can be provided wherein encoding is integrated in the fibre, without the need for attaching a foreign object to the fibre.
  • the present invention relates to an encoded object, the object comprising at least one encoded fibre.
  • the encoded fibre thereby is a microfibre or nanofibre comprising a polymer and a bleachable fluorophore.
  • the fluorophore is spatially bleached so as to generate a code on the fibre.
  • the fibre may be readable by exciting the fluorophore for encoding the object.
  • the encoded fibre may be an electrospun fibre electrospun from a mixture comprising the polymer and the fluorophore .
  • the fluorophore may be immobilized in the polymer matrix in the fibre.
  • the fluorophore may be covalently bound to the polymer in the fibre.
  • the polymer may be safe for use in food or drugs.
  • the fluorophore may be safe for use in food or drugs.
  • the polymer may be any of polystyrene, cellulose-acetate-phthalate or poly(lactic-co- glycolic acid), polyethylene glycol, ethyl cellulose, polyethylene oxide.
  • the fluorophore may be coumarin-6 or fluorescein.
  • the object may be a drug or food and wherein the at least one encoded fibre is added to the drug or food.
  • the object may be a web of fibres comprising the at least one encoded fibre.
  • the present invention also relates to a method for providing an encoded object, the method comprising providing at least one microfibre or nanofibre comprising a polymer and a bleachable fluorophore, locally bleaching the fluorophore so as to generate a code on the fibre.
  • the code may be readable by exciting the fluorophore.
  • Providing a microfibre or nanofibre may comprise electrospinning a microfibre or nanofibre.
  • Electrospinning at least one microfibre or nanofibre may comprise electrospinning a microfibre or nanofibre on a quickly moving surface so as to obtain a susbstantially straight microfibre or nanofibre.
  • Locally bleaching the fluorophore may comprise photobleaching the fluorophore.
  • Providing at least one microfibre or nanofibre may comprise cutting the nanofibre or microfibre.
  • the method may comprise applying a suspension of the locally bleached fibres to the object.
  • the present invention also relates to the use of an encoded object as described above for preventing counterfeit.
  • the method also relates to encoding an object by providing encoded fibres as described in embodiments of the present invention to an object to be encoded.
  • FIG. 1 illustraterates an image of a memobead (A), wherein the code is written by a strong laser source allowing permanent photobleaching, as known from prior art.
  • A a memobead
  • FIG. 1(B) The surface of memobeads is highly functionalized and contains a coating with ferromagnetic properties allowing the correct orientation for efficient readout in a confocal microscopy setup.
  • FIG. 2A to FIG. 2E is a schematic representation of a method for manufacturing encoded systems according to an exemplary embodiment of the present invention.
  • FIG. 3A to FIG. 3C illustrates examples of transmission images of PS-fibres collected at different speeds of the rotating wheel (100 to 1200 rpm), fluorescence images of aligned PS-fibres loaded with FITC(B1 : immediately after spinning; B2 : 1 day after keeping the fibres in open air at room temperature; B3 : 22 hours after dispersing the fibres in water whereby FITC significantly leaks from the fibre into the water and whereby the image B3 is a combined transmission/fluorescence image as the fibres were no longer sufficiently fluorescent), and similar images (CI to C3) as for B but for aligned PS-fibres loaded with coumarin-6.
  • Scale bar is ⁇
  • FIG. 4A to FIG. 4E illustrates fluorescence images of aligned fibres and fibre pieces consisting of polystyrene (PS), ethylcellulose (EC), poly-lactide-co-glycolide (PLGA) or cellulose acetate phthalate (CAP) as matrix polymers and encoded with coumarin-6, according to embodiments of the present invention.
  • Fluorescence images of aligned fibres (A) and fibre pieces (B,C,D) loaded with coumarin-6 are shown. Note that information can be stored , not only in the width of the bars, but as well in the length of the memo-fibres.
  • the inserts in C and D show the barcodes which were written in the fibre pieces, the rectangles indicate one memo-fibre.
  • E shows the contrast of the digital codes in the fibre pieces kept in open air at room temperature.
  • the contrast of the code is defined as the ratio (%) of fluorescence in the bleached segments to the fluorescence in the non-bleached regions in the fibre. Scale bar is ⁇ .
  • FIG. 5 illustrates fluorescence images of encoded fibres consisting of only FDA approved materials according to embodiments of the present invention, whereby poly-lactide-co-glycolide (PLGA), poly-ethylene-oxide (PEO), or ethylcellulose (EC) as matrix polymers and encoded with fluorescein.
  • PLGA poly-lactide-co-glycolide
  • PEO poly-ethylene-oxide
  • EC ethylcellulose
  • FIG. 6 illustrates an example of a web comprising encoded fibres, according to an embodiment of the present invention.
  • fluorophores efficiently lose their flurorescent properties upon bleaching using
  • bleaching can be performed quick.
  • the latter may be obtained by optimizing the irradiation system used, the fiber geometry used and/or the intrinsic bleaching properties of the fluorophore in the polymer.
  • materials being safe for food and/or drugs reference may be made to those materials recognised by an official legislator as being safe in the concentrations used.
  • materials may be Generally Recognized As Safe (GRAS) by the FDA or approved by the FDA as an inactive ingredient, e.g. for the concentrations in which they are used.
  • GRAS Generally Recognized As Safe
  • the present invention relates to encoded objects comprising at least one encoded fibre.
  • the encoded fibre thereby advantageously is a microfibre or nanofibre comprising a polymer and a bleachable fluorophore.
  • the fluorophore thereby is locally bleached so as to generate a code on the fibre, readable by exciting the fluorophore. Providing such code may be done for encoding the object.
  • At least one encoded fibre may be a plurality of fibres, although the invention is not limited thereto and use of a single encoded fibre also is envisaged.
  • the objects may for example be food, drugs, webs, the fibre itself, etc.
  • the at least one encoded fibre especially may be suitable for use in identification of objects, e.g.
  • the fibre may be a short piece of fibre, e.g. cut from a longer piece of fibre, although the invention is not limited thereto.
  • the required length may depend on the size of the code to be implemented.
  • the length of the fibre may be in the range ⁇ to 50 ⁇ , e.g. 500 ⁇ to 50 ⁇ .
  • a microfibrefibre reference may be made to a fibre having an average diameter in the range ⁇ to ⁇ .
  • Such a microfibre may have an average diameter in the range 500 ⁇ to ⁇ , e.g. 200 ⁇ to ⁇ , e.g.
  • the encoded fibre may be an electrospun fibre.
  • the latter may result in a highly aligned fibre, especially when they are made using a method as described in one of the embodiments below. Nevertheless, other electrospinning techniques also may be applied.
  • the fibre advantageously may be made of materials that are safe for use in foods and/or drugs, e.g. Generally Recognized As Safe (GRAS) by the FDA or approved by the FDA as an inactive ingredient, e.g. for the concentrations in which they are used.
  • GRAS Recognized As Safe
  • the fibre may be part of a major class of excipients in oral drugs. It may be made of pharmaceutical materials.
  • the pharmaceutical materials may for example be pharmaceutical polymers, i.e. polymers which are safe for use in food and/or drugs.
  • polymer materials may be used as the basis for the fibre, especially polymer materials which are safe for use in food and/or drugs, e.g. are FDA approved, for use in oral medicines or food, aiming to use them in trace amounts.
  • PS polystyrene
  • EC ethylcellulose
  • CAP cellulose-acetate-phthalate
  • PLGA poly(lactic-co-glycolic acid)
  • PLA polylactic acid
  • PVP poly vinyl phenol
  • PEG polyethylene glycol
  • PEO polyethylene oxide
  • Eudragit RL100 S100, L100, RS100.
  • the microfibre or nanofibre may comprise more than one polymer. In embodiments of the present invention, the microfiber or nanofibre may comprise more than one bleachable fluorophores.
  • the fibres according to embodiments of the present invention contain a bleachable fluorophore or chromophore.
  • the codes on the fibres may be in the form of bleached patterns within the bleachable fluorophore portions of the fibres.
  • the fibres may contain the bleachable fluorophores either on the surface of the fibres (e.g. as coating), or within the body of the fibres. Any reference in this application to the bleaching of fluorophores "on" the fibres includes bleaching at the surface of the fibres as well as bleaching at an internal depth of the fibres.
  • Preferred bleachable fluorophores include bleachable fluorescent or electromagnetic radiation absorbing substances. Examples of fluorophores that can be used include fluorescers, phosphorescers, or scintillators.
  • Bleachable chemiluminescent, bioluminescent, or colored substances may be used.
  • the bleachable substances may be, more specifically, fluorescein, fluorescein isothiocyanate ("FITC"), phycoerythrines, coumarins, lucifer yellow, rhodamine and coumarin-6.
  • the bleachable substances should be chosen so that, when bleaching occurs, the code remains on the fibre for the period of time that is desired for the use of the encoded fibres and any necessary reading of the codes.
  • Bleachable fluorophores also may be selected such that these are food and/or drug safe. Thus, a certain amount of diffusion of non-bleached molecules into the bleached areas is acceptable as long as the useful life of the code is preserved.
  • the latter may be selected as function of the polymer in which the bleachable substance is used.
  • One advantageous combination regarding stability is for example the use of coumarin-6 in polymer materials like polystyrene PS, Cellulose Acetate Phthalate (CAP) or Polylactic glycolic acid (PLGA).
  • the fluorophores advantageously are selected such that they are sufficiently dissolved and stable in the solvent(s) used to solve the polymers.
  • the suggested methods of application result in fluorophores that are sufficiently and homogenously encapsulated in the fibres.
  • the fibres according to embodiments of the present invention may be encoded by local photolysis or photobleaching of a substance.
  • the codes written on the fibres may be of any geometry, design, or symbol that can be written and read on the fibres.
  • the codes may be written as numbers or letters, or as codes in the form of symbols, pictures, bar codes, ring codes, or three-dimensional codes.
  • ring codes are used, which are similar to bar codes, except that concentric circles are used rather than straight lines.
  • a ring may contain, for example, the same information as one bar.
  • the codes may be written on the surface of the fibres or at an internal depth of the fibres.
  • the codes may be written at an internal depth of the fibres, and more particularly in a center plane of the fibres.
  • the center plane may be a preferable location for writing the code because it may provide the largest surface area available for writing. Furthermore, for microcarriers having curved surfaces, it may be more advantageous to write the codes at an internal depth rather than on the curved surfaces. This is because it may often be more convenient to write and read the codes on a flat plane rather than on a curved surface. It is an advantage of embodiments according to the present invention that in an efficient manner unique codes can be applied, resulting in the possibility to provide different objects with a unique encoding. The latter may for example be done by bleaching fluorophores using unique codes with a programmed system generating such unique codes. If the same codes are used for more than one object, embodiments of the present invention also allow to switch in code easily for subsequent objects, when required.
  • Codes bleached on fibres may also be written to have different intensities of fluorescence or color within bleached areas of the fibres.
  • a bleached coding may contain several different degrees of bleaching, thereby having several different intensities of fluorescence within the bleached region as a whole.
  • fibres may be encoded not only by the geometry of the pattern bleached on the fibres, but also by the use of different fluorescent intensities within the pattern. While the invention has been illustrated and described in detail in the drawings and foregoing description, such illustration and description are to be considered illustrative or exemplary and not restrictive. The invention is not limited to the disclosed embodiments.
  • the fibres advantageously are substantially straight with a deviation from linearity of less than 20%, allowing to obtain a good writeability and readability of the fibres
  • Interaction between the polymer and the fluorophores may be selected such that the mobility of the fluorophores is low or zero.
  • the fluorophores may be covalently bound to the polymer in the fibre or immobilized by hydrophobic or non-covalent interactions such as charge-charge, charge-dipole or hydrogen bonding interactions. Immobilisation of the fluorescent compound may e.g. be established by attaching the bleaching agent covalently to the polymer, i.e. to the polymer chains.
  • the present invention relates to a method for obtaining encoded fibres or objects comprising such fibres. It is an advantage of embodiments according to the present invention that it makes use of simple techniques and provides encoded fibres which can be easily read for identifying objects.
  • the method may be especially suitable for providing encoded objects as described in device embodiments according to the present invention.
  • the method comprises providing at least one microfibre or nanofibre comprising a polymer and a bleachable fluorophore and locally bleaching the fluorophore so as to generate a code on the fibre.
  • the code may be readable by exciting the fluorophore.
  • Providing a microfibre or nanofibre advantageously may be performed by electrospinning a fibre. It is an advantage of electrospinning that it is a simple technique, allowing preparation of the most simple polymeric matrices from a large variety of pharmaceutical polymers.
  • Electrospinning provides the advantage that fibres can be made using a mixture comprising polymers and fluorophores such that embedding of fluorophores in the polymer matrix inherently is present and no subsequent processing step is required. This also may assist in the immobilisation of the fluorophores in the polymer matrix. It is also an advantage of electrospinning that straight and optionally aligned microfibres can be obtained. Using straight fibres may assist in providing encoded fibres that are less prone to reading difficulties. Alignment may advantageously be used whenmultiple fibres are generated at the same time. The latter may reduce the economic and time cost for manufacturing the encoded fibres.
  • Straight fibres and/or aligned fibres furthermore may allow encoding using a scanning laser beam for locally destroying fluorophores.
  • Straight and or aligned fibres may be obtained by electrospinning the microfibre or nanofibre on a quickly moving receiving surface. In one embodiment, such fibres may be obtained using a conventional electrospinning dope and a rotating drum at high speed as collector.
  • the method also comprises locally bleaching the fluorophores for generating a code.
  • the local bleaching may be performed by photobleaching or photolysis. Spatial selective photobleaching may be performed by exposing well selected regions with radiation, e.g. laser radiation. The latter is illustrated in Figure 2D.
  • photobleaching makes use of photobleaching, as this allows obtaining immobilised fluorophores in the fibres at room temperature, resulting in less disappearance of the encoding as the fluorophores are prevented from becoming mobile which would result in recovery of the fluorescence in the bleached zones.
  • Another example of photobleaching may be illumination through a mask whereby the fibres may be encoded by fotobleaching using a source and passing the source rays at the appropriate positions of the mask, which results in providing the fibres with a unique coding.
  • the mask may also contain holes through which a high energy ray can pass to cut the fibre into small pieces, as described in a different step.
  • the fibres also may be cut into smaller pieces and the smaller pieces of fibre may be used as encoded fibres for encoding objects.
  • Cutting of longer fibres may be performed using for example cold ablation, although the invention is not limited thereto, cutting also may be performed by templating or by razor cutting.
  • the length of the fibres may be in the range ⁇ to 50 ⁇ , e.g. in the range 500 ⁇ to 50 ⁇ . By way of illustration, cutting is shown in Figure 2C.
  • Cutting and encoding may be performed in any suitable order, i.e. first encoding then cutting, first cutting then encoding or performing cutting and encoding simultaneously.
  • the method also may comprise the step of applying encoded fibres to a larger object to be encoded.
  • the latter may for example be obtained by mixing the fibres into the object to be encoded, providing the fibres to a surface of the object to be encoded, etc.
  • Providing the fibres to a surface of the object to be encode may for example be obtained by making a suspension of the locally bleached fibres and applying the suspension to the object. After drying the fibres may be automatically fixed to the surface of the object.
  • the fibres thus may be brought into a liquid to form a dispersion, of which a drop is brought onto any appropriate surface (drug, packaging, ).
  • the objects encoded are oral medicines, in particular tablets or capsules containing drugs.
  • encoded fibres such as for example encoded micron sized fibres or encoded nano sized fibres made from pharmaceutical materials, are used for encoding drugs.
  • Fluorophores are immobilised in glassy polymer fibres, resulting in stable encoding of objects. The latter is obtained by selecting the glass transition temperature of the polymer fibre and the physicochemical interactions between the fluorophore and the polymer appropriately resulting in encoding by photobleaching that is stable over long periods.
  • the encoded fibres at the tablet's surface can be easily decoded using a basic fluorescence microscope, even without removing the fibre pieces from the tablets.
  • fibres can be made of those pharmaceutical ingredients having already been used for decades in tablets and other types of oral medicines. All drugs could make use of such encoding, such as for example today's "lifestyle drugs” like e.g. sexual performance enhancers, smoking cessation agents, antibiotics, painkillers, anti-malarial or HIV drugs. Similarly, such polymers also can be used for identifying authentic food, etc.
  • lifestyle drugs like e.g. sexual performance enhancers, smoking cessation agents, antibiotics, painkillers, anti-malarial or HIV drugs.
  • polymers also can be used for identifying authentic food, etc.
  • the encoded fibres remain harmless after encoding and can be decoded using a fast detection technique, as the orientation of the orientation of the fibre and the code can be easily determined., allowing to use such methods against counterfeiting also in developing countries.
  • fast and low cost detection is obtained.
  • Microfibres were obtained by electrospinning polymer solutions containing a fluorophore (Table 1), using an electrospinning setup. Two arguments explain our choice for electrospinning. Firstly, it is a remarkably simple technique that allows preparing the most simple polymeric matrices from a wealth of pharmaceutical polymers. Secondly, electrospinning allows aligning the microfibres which is a requirement when encoding the fibres by a scanning laser beam that locally destroys the fluorophores.
  • FIG. 2A An electrospinning setup as can for example be used is shown in Figure 2A, indicating a power supply 202, one or more syringe 204 with a flat tip needle 205 and optionally a pump pressure providing means 206 and a grounded collector 208.
  • the collector may comprise a glass support 210.
  • Such systems are known by the person skilled in the art.
  • a droplet of the polymer/fluorophore solution is formed at the tip of the needle by surface tension while charge is induced on the droplet surface by an electric field. When the electric field reaches a critical value at which the electric force overcomes the surface tension of the droplet, a charged jet is ejected from the tip.
  • a rotating collector 208 is used fitted with a glass support, as shown in Figure 2B to collect aligned fibres 220.
  • a motor 212 may be provided for rotating the collector 208. It is an advantage of at least some embodiments of the present invention that the fibres during electrospinning are collected on a moving surface so that aligned fibres can be generated.
  • the fibres 220 on the glass support were dried in open air.
  • water can be used as solvent, such as for example with the combination PEO and flurorescein.
  • Fluorescein is a common water- soluble fluorophore. Fluorescein capsules are taken by patients to diagnose ophthalmologic diseases. The fibres were loaded with the fluorescein derivative fluoresceinisothiocyanate (FITC), which is soluble in dimethylformamide DMF and tetrahydrofuran THF used to solve PS, EC, CAP and PLGA.
  • FITC fluorescein derivative fluoresceinisothiocyanate
  • 3B part 1 shows that PS-fibres can be homogeneously loaded with FITC (the brighter portions indicating the fluorescent portions) though, one day after keeping the fibres in open air at room temperature, FITC seems to have significantly migrated towards the surface of the fibres, as can be seen in FIG. 3B part 2 wherein the brighter portions are now at the edges of the fibres. Furthermore, especially upon dispersion in water, FITC significantly leaks from the fibres into the water, as can be seen in FIG. 3B part 3 where the brighter portions are not or less significant present in or at the edges of the fibres. An insufficient immobilization of FITC in the PS-fibre and a too high solubility in water made FITC less suitable.
  • An advantageous fluorophore is for example coumarin-6.
  • FIG. 3C shows, even after 4 days' storage in open air (FIG. 3C part 2) and after one day being dispersed in water (FIG. 3C, part 3), PS-fibres loaded with coumarin-6 remained homogeneously coloured.
  • FIG. 3c shows the fluorescence of the fibres just after manufacturing. This was not only the case for PS-fibres, coumarin-6 seemed also well suited to design stable homogeneously coloured ethylcellulose (EC), cellulose-acetate-phthalate (CAP), and poly(lactic-co-glycolic acid) (PLGA)-microfibres.
  • FIG. 3C shows, even after 4 days' storage in open air (FIG. 3C part 2) and after one day being dispersed in water (FIG. 3C, part 3), PS-fibres loaded with coumarin-6 remained homogeneously coloured.
  • FIG. 3c shows, even after 4 days
  • FIG. 4A illustrates aligned fibres for (from left to right) polystyrene (PS), ethylcellulose (EC), poly(lactic-co- glycolic acid) (PLGA) and cellulose-acetate-phthalate (CAP) microfibres.
  • PS polystyrene
  • EC ethylcellulose
  • PLGA poly(lactic-co- glycolic acid)
  • CAP cellulose-acetate-phthalate
  • a scanning UV laser could cut the aligned fibres into 100-200 ⁇ long pieces (from left to right : polystyrene (PS), ethylcellulose (EC), poly(lactic-co-glycolic acid) (PLGA) and cellulose-acetate-phthalate (CAP) microfibres).
  • PS polystyrene
  • EC ethylcellulose
  • PLGA poly(lactic-co-glycolic acid)
  • CAP cellulose-acetate-phthalate
  • the fluorescent fibre pieces were encoded with a code 250 by spatial selective photobleaching by exposing well selected regions to a 488 nm laser beam, i.e.
  • FIG. 2D shows an encoding device 260, as shown in FIG. 2D.
  • An in-house-developed encoding device was used, being a laser scanning confocal microscope (Nikon) equipped with an argon laser and an acousto-optic modulator.
  • FIG. 4C shows that the coumarin-6 loaded fibre pieces could be digitally encoded by photobleaching by a laser beam scanning along the longitudinal axis of the fibre pieces (from left to right : polystyrene (PS), ethylcellulose (EC), poly(lactic- co-glycolic acid) (PLGA) and cellulose-acetate-phthalate (CAP) microfibres) according to a process as shown in FIG. 2D.
  • PS polystyrene
  • EC ethylcellulose
  • PLGA poly(lactic- co-glycolic acid)
  • CAP cellulose-acetate-phthalate
  • the encoded fibre pieces (which also may be referred to as "memofibres'), were dispersed in water, simply by applying a drop of water on the fibre pieces on the glass support. It is advantageous to obtain a stable code. Clearly, the more mobile the fluorophore in the polymer fibres, the faster the digital code will disappear.
  • the contrast should be sufficiently high.
  • This contrast is determined by the mobility of the photobleached or unbleached fluorophores and advantageously of both the photobleached and unbleached fluorophores in the fibres, which is influenced by the particular fluorophore used in combination with the composition and structure of the fibre.
  • At least a fraction of the photobleached or unbleached and advantageously of both the photobleached and unbleached fluorophores should be immobile or behave substantially immobile, as the contrast is in the end determined by such immobile or substantially immobile fraction. Numerical calculation techniques are known in the art for determining how the contrast will lower over time.
  • Embodiments of the present invention thus also include using numerical calculation techniques for determining whether sufficient contrast for a certain fluorophore and fibre exists. Alternatively, also long term experiments could be applied. If one assumed coumarin-6 diffusing in water, one could easily calculate from Stokes- Einstein law that it would take only seconds to travel a few micrometers.
  • FIG. 4E shows the contrast of the codes as a function of time (for polystyrene (PS), ethylcellulose (EC), cellulose-acetate-phthalate (CAP), and poly(lactic-co-glycolic acid) (PLGA)-microfibres).
  • PS polystyrene
  • EC ethylcellulose
  • CAP cellulose-acetate-phthalate
  • PLGA poly(lactic-co-glycolic acid)
  • 4D shows the fluorescence images (the brighter portions are indicative of the fluorescence in the fibres) we obtained from fibres at the surface of tablets using a simple fluorescence microscope (from left to right : polystyrene (PS), ethylcellulose (EC), poly(lactic-co-glycolic acid) (PLGA) and cellulose- acetate-phthalate (CAP) microfibres).
  • PS polystyrene
  • EC ethylcellulose
  • PLGA poly(lactic-co-glycolic acid)
  • CAP cellulose- acetate-phthalate
  • FIG. 5 shows the fluorescence images of encoded fibres that are composed entirely of substances that are on the FDA's list of inactive ingredients (FDA's Inactive Ingredient Guide, http://www.accessdata.fda.gov/scripts/cder/iig/index.cfm) as substances already used in oral dosage forms.
  • Fluorescent microfibers are obtained by electrospinning a solution of fluorescein together with different matrix polymers (from left to right :poly(lactic-co-glycolic acid), poly-elthylene-oxide (PEO) andethylcellulose (EC)).
  • the digital codes are obtained by spatio-selective photobleaching of the fluorescein, and are perfectly readable (the brighter portions are indicative of the fluorescence in the fibres) using a simple non-confocal fluorescence microscope
  • the electrospinning conditions used for manufacturing the fibres shown 5 are illustrated in Table 2.
  • the objects are a web comprising encoded fibres.
  • the web may be a fibre-web and may be used in a plurality of applications, such as for example in encoded textiles like for wearable clothing, software carriers, perfumes, tobacco products, medical devices, drug formulations.
  • encoded textiles like for wearable clothing, software carriers, perfumes, tobacco products, medical devices, drug formulations.
  • fibres in such a web may be loaded with different types of bioactive compounds (like e.g.
  • each fibre loaded with another growth factor) to be locally released to cells which are supported by the web the codes in the fibre may allow to identify to which types of drugs cells in specific areas of a web were exposed.
  • An advantage of having a web as object comprising encoded fibres is that the web itself can be used directly in a variety of applications where identification and/or prevention of counterfeiting can be important. Materials used and techniques used for producing the web may be similar as described above, although the invention is not limited thereto.
  • FIG. 6 shows a polystyrene microfibre web that was obtained by electrospinning polystyrene solution containing a coumarine-6.
  • the fluorescent fibre pieces webs (while still on the glass support) were encoded by spatial selective photobleaching by exposing well selected regions to a high intensity 488 nm laser beam.
  • An in-house-developed encoding device was used, being a laser scanning confocal microscope (Nikon Benelux, Brussels, Belgium) equipped with an Aerotech ALS3600 scanning stage, a SpectraPhysics 2060 argon laser, and an Acousto-Optic Modulator.
  • the fluorescent molecules lost their fluorescence, giving rise to the code.
  • Different barcode could be encoded at different position of polystyrene web. The latter could for example also be used for localization of different positions in a web. The latter illustrates some possibilities and features of some embodiments of the present invention.
  • a 100 ⁇ fibre contains as little as 0.1 picogram coumarin-6. If one applies 10 fibres per encoding of a tablet of drugs and assume a patient would take 10 tablets a day, the daily intake of coumarin-6 would be around 10 picogram. Thus, even if a fluorophore is not declared safe for use in food of drugs (yet), depending on legislation it may be considered an impurity and an "impurity" in a drug formulation can, depending on legislation, be allowed as long as the daily intake remains lower than 1.5 microgram.
  • a computer program for performing at least part of the method may be stored/distributed on a suitable medium, such as an optical storage medium or a solid-state medium supplied together with or as part of other hardware, but may also be distributed in other forms, such as via the Internet or other wired or wireless telecommunication systems. Any reference signs in the claims should not be construed as limiting the scope.

Abstract

The present invention relates to an encoded object, the object comprising at least one encoded fibre. The encoded fibre thereby is a microfibre or nanofibre comprising a polymer and a bleachable fluorophore. The fluorophore is spatially bleached so as to generate a code on the fibre readable by exciting the fluorophore for encoding the object.

Description

Encoded fibres
Field of the invention
The present invention relates to the field of encoding of objects. More particularly, the present invention relates to a method and system for encoding fibres, e.g. for use in counteracting counterfeiting, as well as to fibres thus obtained or objects comprising such fibres.
Background of the invention Official health institutes recognize that drug counterfeiting is an ever increasing hazard to unaware consumers. Especially considering the rising popularity of purchasing drugs via the internet, counterfeit drugs are becoming widespread. In industrialized countries, particularly today's "lifestyle drugs" (e.g. sexual performance enhancers, smoking cessation agents) are targeted for easy profit. However, in developing countries antibiotics, painkillers, anti-malarial and HIV drugs are also being counterfeited. All too often, such counterfeits have caused patients' deaths.
To combat counterfeiting, the packaging of an increasing number of drugs is being 'protected' by radio frequency tags, barcodes, watermarks, fluorescent inks, chemical or biological (DNA) tags. Unfortunately, such tracking technologies are only effective if the drugs are not repackaged. Manufacturers often do not ship drugs directly to hospitals and dispensing pharmacies. Generally, drugs are sold to Wholesalers or Distributors who repackage drugs from bulk to unit-of-use containers which provide a means for counterfeit drugs to enter the legitimate drug supply chain. An authentic package does not therefore, certify authentic content. To overcome this, "in-drug labelling" itself, instead of on the drug packaging, could help defeat drug counterfeiters. Nowadays, the incorporation of taggants (like colour- coded particles and mica particles coated with the colorants titanium oxide and/or iron oxide) in drug formulations is seldom used; one major reason being that it requires extensive toxicological screening of the taggant and formulation compatibility testing.
Tablets are the most widely used drug dosage form in the world. Recently we introduced digitally encoded polystyrene micro-particles (named 'memobeads') for the in-product labelling of tablets; information is written in the middle plane of fluorescently dyed microspheres by 'spatial selective photobleaching' of the fluorescence by the use of a confocal laser scanning microscope. 'On-tablet laser NanoEncryption' was also announced, to write digital codes on the surface of tablets. By way of illustration, a confocal image of the middle plane of a memobead is shown in FIG. 1(A). The code 10 is written by "spatial selective photobleaching" of the fluorescence in dyed polystyrene microspheres. Regions at a certain depth in the microspheres are bleached by the use of a confocal laser scanning microscope. Because the fluorescent dye molecules are immobilized in the polystyrene matrix, the bleached dye molecules stay in place which prevents the code from fading away over time. In FIG. 1(B) the surface of memobeads is highly functionalized and contains ferromagnetic Cr02 nanoparticles 20 embedded in a coating of polyelectrolytes 30. The ferromagnetic properties of the coating allow orienting the beads correctly in a magnetic field which is necessary to make the code readable by a confocal fluorescence microscope.
There has been also an interest in Raman spectroscopy to analyse the composition of the pharmaceutical excipients of a tablet. Indeed, such an "excipient- fingerprint" could also be a tool to track down counterfeiters. Clearly, the future of Raman imaging of pharmaceutical excipients will need skilled personnel and expensive instruments, meanwhile, developing countries continue to suffer severely from counterfeited drugs.
In "Polydiacetylene Supramolecules in Electrospun Microfibres : Fabrication, Micropatterning, and Sensor Applications", Chae et al. discuss in Advanced Materials 2007, vol. 17 p 521-524 the fabrication of polymer fibres wherein polydiacetylene supramolecules are embedded. Photomasked UV irradiation of such a fibre resulted in patterned images. Summary of the invention
It is an object of embodiments of the present invention to provide good methods and systems for encoding objects, as well as objects thus obtained. It is an advantage of embodiments according to the present invention that efficient manufacturing as well as efficient read-out of the obtained encoded objects can be obtained. It is an advantage of embodiments according to the present invention that due to the cylindrical geometry of the polymer fibres a complicated step for providing a proper orientation of the fibres is not necessary for decoding. Regardless of the position of the fibres the codes are readable.
It is an advantage of embodiments according to the present invention that encoded objects can be obtained which are safe for use in food or drugs. The encoded fibres may for example be used in drugs in order to encode the drugs and prevent counterfeiting. It is an advantage of embodiments according to the present invention that the encoding also can be applied to food and drugs as the fibres can be made of materials approved for use in food and/or drugs. It is an advantage of embodiments according to the present invention that such particles can easily be introduced on the item to be protected and is not restricted to introduction on the package or to direct introduction of a code on the product itself.
It is an advantage of some embodiments according to the present invention that encoding can be provided on nano-fibres or more particular short portions thereof, resulting, optionally using a suitable background, in the nano-fibres being not easily visible with the naked eye. The latter may not only improve applications for counterfeiting, but it also may reduce any disturbing effects for consumers of products encoded, e.g. to avoid counterfeiting.
It is an advantage of embodiments according to the present invention that a non- limited number of different codes can be introduced in a production and cost efficient manner. It is an advantage of embodiments according to the present invention that labelling of individual objects, e.g. labelling of tablets, also referred to as one-dose marking, can be applied, providing a more powerful strategy against counterfeiting.
It is an advantage of embodiments according to the present invention that methods and systems are provided allowing obtaining nano-sized encoded objects, of which the code can advantageously easily be read. It thereby is an advantage of embodiments according to the present invention that clear preferred direction is present in the objects, making encoding and reading of codes easier.
It is an advantage of embodiments according to the present invention that methods, systems and products thus obtained can make use of bleaching for encoding the fibres.
It is an advantage of embodiments according to the present invention that fibres can be provided wherein encoding is integrated in the fibre, without the need for attaching a foreign object to the fibre.
It is an advantage of embodiments according to the present invention that reading of codes for the objects according to the present invention can be easily obtained. It is an advantage of some embodiments according to the present invention that due to the aligning of the fibres during production, immediate and simple encoding and detection of codes can be obtained.
It is an advantage of embodiments according to the present invention that easy production of encoded fibres, e.g. nano-fibres, can be obtained. It is an advantage of embodiments according to the present invention that making of encoded fibres such as for example fluorescent nano-fibres, is a one step process.
It is an advantage that e.g. a relatively cheap non-confocal fluorescence microscope can be used for reading the codes. The above objective is accomplished by a method and device according to the present invention.
The present invention relates to an encoded object, the object comprising at least one encoded fibre. The encoded fibre thereby is a microfibre or nanofibre comprising a polymer and a bleachable fluorophore. The fluorophore is spatially bleached so as to generate a code on the fibre. The fibre may be readable by exciting the fluorophore for encoding the object.
The encoded fibre may be an electrospun fibre electrospun from a mixture comprising the polymer and the fluorophore .
The fluorophore may be immobilized in the polymer matrix in the fibre.
The fluorophore may be covalently bound to the polymer in the fibre.
The polymer may be safe for use in food or drugs.
The fluorophore may be safe for use in food or drugs.
The polymer may be any of polystyrene, cellulose-acetate-phthalate or poly(lactic-co- glycolic acid), polyethylene glycol, ethyl cellulose, polyethylene oxide.
The fluorophore may be coumarin-6 or fluorescein.
The object may be a drug or food and wherein the at least one encoded fibre is added to the drug or food.
The object may be a web of fibres comprising the at least one encoded fibre.
The present invention also relates to a method for providing an encoded object, the method comprising providing at least one microfibre or nanofibre comprising a polymer and a bleachable fluorophore, locally bleaching the fluorophore so as to generate a code on the fibre. The code may be readable by exciting the fluorophore. Providing a microfibre or nanofibre may comprise electrospinning a microfibre or nanofibre.
Electrospinning at least one microfibre or nanofibre may comprise electrospinning a microfibre or nanofibre on a quickly moving surface so as to obtain a susbstantially straight microfibre or nanofibre.
Locally bleaching the fluorophore may comprise photobleaching the fluorophore. Providing at least one microfibre or nanofibre may comprise cutting the nanofibre or microfibre.
The method may comprise applying a suspension of the locally bleached fibres to the object.
The present invention also relates to the use of an encoded object as described above for preventing counterfeit. In one aspect the method also relates to encoding an object by providing encoded fibres as described in embodiments of the present invention to an object to be encoded.
Particular and preferred aspects of the invention are set out in the accompanying independent and dependent claims. Features from the dependent claims may be combined with features of the independent claims and with features of other dependent claims as appropriate and not merely as explicitly set out in the claims. These and other aspects of the invention will be apparent from and elucidated with reference to the embodiment(s) described hereinafter. Brief description of the drawings
TABLE 1 Parameters used for electrospinning of polymers in example of embodiments according to the present invention.
TABLE 2 Parameters used for electrospinning of polymers in another example of embodiments according to the present invention.
FIG. 1 -illustrates an image of a memobead (A), wherein the code is written by a strong laser source allowing permanent photobleaching, as known from prior art. In
FIG. 1(B) The surface of memobeads is highly functionalized and contains a coating with ferromagnetic properties allowing the correct orientation for efficient readout in a confocal microscopy setup.
FIG. 2A to FIG. 2E is a schematic representation of a method for manufacturing encoded systems according to an exemplary embodiment of the present invention.
Schematic representation of the synthesis of memo-fibres. A) Electrospinning setup.
B) Aligned polymer fibres deposited by electrospinning on the glass support. C)
Cutting of the polymer fibres into fibre pieces by cold ablation. D) Encoding of the fibre pieces by photobleaching through the use of a scanning laser beam. E) Applying a few micro-litres of a memo-fibre dispersion on the surface of a tablet.
FIG. 3A to FIG. 3C illustrates examples of transmission images of PS-fibres collected at different speeds of the rotating wheel (100 to 1200 rpm), fluorescence images of aligned PS-fibres loaded with FITC(B1 : immediately after spinning; B2 : 1 day after keeping the fibres in open air at room temperature; B3 : 22 hours after dispersing the fibres in water whereby FITC significantly leaks from the fibre into the water and whereby the image B3 is a combined transmission/fluorescence image as the fibres were no longer sufficiently fluorescent), and similar images (CI to C3) as for B but for aligned PS-fibres loaded with coumarin-6. Scale bar is ΙΟΟμιη
FIG. 4A to FIG. 4E illustrates fluorescence images of aligned fibres and fibre pieces consisting of polystyrene (PS), ethylcellulose (EC), poly-lactide-co-glycolide (PLGA) or cellulose acetate phthalate (CAP) as matrix polymers and encoded with coumarin-6, according to embodiments of the present invention. Fluorescence images of aligned fibres (A) and fibre pieces (B,C,D) loaded with coumarin-6 are shown. Note that information can be stored , not only in the width of the bars, but as well in the length of the memo-fibres. The inserts in C and D show the barcodes which were written in the fibre pieces, the rectangles indicate one memo-fibre. E) shows the contrast of the digital codes in the fibre pieces kept in open air at room temperature. The contrast of the code is defined as the ratio (%) of fluorescence in the bleached segments to the fluorescence in the non-bleached regions in the fibre. Scale bar is ΙΟΟμιη.
FIG. 5 illustrates fluorescence images of encoded fibres consisting of only FDA approved materials according to embodiments of the present invention, whereby poly-lactide-co-glycolide (PLGA), poly-ethylene-oxide (PEO), or ethylcellulose (EC) as matrix polymers and encoded with fluorescein.
FIG. 6 illustrates an example of a web comprising encoded fibres, according to an embodiment of the present invention.
The drawings are only schematic and are non-limiting. In the drawings, the size of some of the elements may be exaggerated and not drawn on scale for illustrative purposes.
Detailed description of illustrative embodiments
Where in embodiments according to the present invention reference is made to a bleachable fluorophore, reference is made to a fluorophore that, upon a predetermined excitation, undergoes a structural change such that its fluorescent property disappears. Advantageously in embodiments of the present invention, fluorophores efficiently lose their flurorescent properties upon bleaching using
Advantageously, bleaching can be performed quick. The latter may be obtained by optimizing the irradiation system used, the fiber geometry used and/or the intrinsic bleaching properties of the fluorophore in the polymer.
Where in embodiments of the present invention reference is made to an "encoded fibre" or "fibre", no limitation is given on the length of the fibre and consequently also a piece of fibre cut from a larger fibre are envisaged by this terminology.
Where in embodiments of the present invention reference is made to glass polymers, reference is made to polymers having an amorpheous polymer matrix.
Where in embodiments of the present invention reference is made to materials being safe for food and/or drugs, reference may be made to those materials recognised by an official legislator as being safe in the concentrations used. For example, materials may be Generally Recognized As Safe (GRAS) by the FDA or approved by the FDA as an inactive ingredient, e.g. for the concentrations in which they are used.
In a first aspect, the present invention relates to encoded objects comprising at least one encoded fibre. The encoded fibre thereby advantageously is a microfibre or nanofibre comprising a polymer and a bleachable fluorophore. The fluorophore thereby is locally bleached so as to generate a code on the fibre, readable by exciting the fluorophore. Providing such code may be done for encoding the object. At least one encoded fibre may be a plurality of fibres, although the invention is not limited thereto and use of a single encoded fibre also is envisaged. The objects may for example be food, drugs, webs, the fibre itself, etc. The at least one encoded fibre especially may be suitable for use in identification of objects, e.g. for preventing counterfeiting of objects, such as for example food, drugs, etc, although the invention is not limited thereto. The fibre may be a short piece of fibre, e.g. cut from a longer piece of fibre, although the invention is not limited thereto. The required length may depend on the size of the code to be implemented. In some examples, the length of the fibre may be in the range ΙΟΟΟμιη to 50μιη, e.g. 500μιη to 50μιη. In embodiments of the present application with a microfibrefibre reference may be made to a fibre having an average diameter in the range ΙΟΟΟμιη to Ιμιη. Such a microfibre may have an average diameter in the range 500μιη to Ιμιη, e.g. 200μιη to Ιμιη, e.g. 50μιη to Ιμιη, e.g. 5μιη to Ιμιη. In embodiments of the present application with a nanofibre reference may be made to a fibre having an average diameter in the range less than Ιμιη to lOnm Advantageously, the encoded fibre may be an electrospun fibre. The latter may result in a highly aligned fibre, especially when they are made using a method as described in one of the embodiments below. Nevertheless, other electrospinning techniques also may be applied. For food and drug applications, the fibre advantageously may be made of materials that are safe for use in foods and/or drugs, e.g. Generally Recognized As Safe (GRAS) by the FDA or approved by the FDA as an inactive ingredient, e.g. for the concentrations in which they are used. It thereby is an advantage of embodiments according to the present invention that nanofibres can be used, resulting in only a small amount of material being introduced. The fibre may be part of a major class of excipients in oral drugs. It may be made of pharmaceutical materials. The pharmaceutical materials may for example be pharmaceutical polymers, i.e. polymers which are safe for use in food and/or drugs. It is an advantage of embodiments according to the present invention that polymer materials may be used as the basis for the fibre, especially polymer materials which are safe for use in food and/or drugs, e.g. are FDA approved, for use in oral medicines or food, aiming to use them in trace amounts. Some examples of materials that may be used, although the invention is not limited thereto are polystyrene (PS), ethylcellulose (EC), cellulose-acetate-phthalate (CAP), and poly(lactic-co-glycolic acid) (PLGA), polylactic acid (PLA), poly vinyl phenol (PVP),polyethylene glycol( PEG), polyethylene oxide (PEO), Eudragit RL100, S100, L100, RS100.
In embodiments of the present invention, the microfibre or nanofibre may comprise more than one polymer. In embodiments of the present invention, the microfiber or nanofibre may comprise more than one bleachable fluorophores.
The fibres according to embodiments of the present invention contain a bleachable fluorophore or chromophore. The codes on the fibres may be in the form of bleached patterns within the bleachable fluorophore portions of the fibres. The fibres may contain the bleachable fluorophores either on the surface of the fibres (e.g. as coating), or within the body of the fibres. Any reference in this application to the bleaching of fluorophores "on" the fibres includes bleaching at the surface of the fibres as well as bleaching at an internal depth of the fibres. Preferred bleachable fluorophores include bleachable fluorescent or electromagnetic radiation absorbing substances. Examples of fluorophores that can be used include fluorescers, phosphorescers, or scintillators. Bleachable chemiluminescent, bioluminescent, or colored substances may be used. The bleachable substances may be, more specifically, fluorescein, fluorescein isothiocyanate ("FITC"), phycoerythrines, coumarins, lucifer yellow, rhodamine and coumarin-6. The bleachable substances should be chosen so that, when bleaching occurs, the code remains on the fibre for the period of time that is desired for the use of the encoded fibres and any necessary reading of the codes. Bleachable fluorophores also may be selected such that these are food and/or drug safe. Thus, a certain amount of diffusion of non-bleached molecules into the bleached areas is acceptable as long as the useful life of the code is preserved. The latter may be selected as function of the polymer in which the bleachable substance is used. One advantageous combination regarding stability is for example the use of coumarin-6 in polymer materials like polystyrene PS, Cellulose Acetate Phthalate (CAP) or Polylactic glycolic acid (PLGA). The fluorophores advantageously are selected such that they are sufficiently dissolved and stable in the solvent(s) used to solve the polymers. The suggested methods of application result in fluorophores that are sufficiently and homogenously encapsulated in the fibres.
The fibres according to embodiments of the present invention may be encoded by local photolysis or photobleaching of a substance. The codes written on the fibres may be of any geometry, design, or symbol that can be written and read on the fibres. For example, the codes may be written as numbers or letters, or as codes in the form of symbols, pictures, bar codes, ring codes, or three-dimensional codes. Advantageously, ring codes are used, which are similar to bar codes, except that concentric circles are used rather than straight lines. A ring may contain, for example, the same information as one bar. The codes may be written on the surface of the fibres or at an internal depth of the fibres. For example, the codes may be written at an internal depth of the fibres, and more particularly in a center plane of the fibres. The center plane may be a preferable location for writing the code because it may provide the largest surface area available for writing. Furthermore, for microcarriers having curved surfaces, it may be more advantageous to write the codes at an internal depth rather than on the curved surfaces. This is because it may often be more convenient to write and read the codes on a flat plane rather than on a curved surface. It is an advantage of embodiments according to the present invention that in an efficient manner unique codes can be applied, resulting in the possibility to provide different objects with a unique encoding. The latter may for example be done by bleaching fluorophores using unique codes with a programmed system generating such unique codes. If the same codes are used for more than one object, embodiments of the present invention also allow to switch in code easily for subsequent objects, when required.
Codes bleached on fibres may also be written to have different intensities of fluorescence or color within bleached areas of the fibres. For example, a bleached coding may contain several different degrees of bleaching, thereby having several different intensities of fluorescence within the bleached region as a whole. Thus, fibres may be encoded not only by the geometry of the pattern bleached on the fibres, but also by the use of different fluorescent intensities within the pattern. While the invention has been illustrated and described in detail in the drawings and foregoing description, such illustration and description are to be considered illustrative or exemplary and not restrictive. The invention is not limited to the disclosed embodiments.
As indicated above, the fibres advantageously are substantially straight with a deviation from linearity of less than 20%, allowing to obtain a good writeability and readability of the fibres
Interaction between the polymer and the fluorophores may be selected such that the mobility of the fluorophores is low or zero. The fluorophores may be covalently bound to the polymer in the fibre or immobilized by hydrophobic or non-covalent interactions such as charge-charge, charge-dipole or hydrogen bonding interactions. Immobilisation of the fluorescent compound may e.g. be established by attaching the bleaching agent covalently to the polymer, i.e. to the polymer chains. In a second aspect, the present invention relates to a method for obtaining encoded fibres or objects comprising such fibres. It is an advantage of embodiments according to the present invention that it makes use of simple techniques and provides encoded fibres which can be easily read for identifying objects. The method may be especially suitable for providing encoded objects as described in device embodiments according to the present invention. The method comprises providing at least one microfibre or nanofibre comprising a polymer and a bleachable fluorophore and locally bleaching the fluorophore so as to generate a code on the fibre. The code may be readable by exciting the fluorophore. Providing a microfibre or nanofibre advantageously may be performed by electrospinning a fibre. It is an advantage of electrospinning that it is a simple technique, allowing preparation of the most simple polymeric matrices from a large variety of pharmaceutical polymers. Electrospinning provides the advantage that fibres can be made using a mixture comprising polymers and fluorophores such that embedding of fluorophores in the polymer matrix inherently is present and no subsequent processing step is required. This also may assist in the immobilisation of the fluorophores in the polymer matrix. It is also an advantage of electrospinning that straight and optionally aligned microfibres can be obtained. Using straight fibres may assist in providing encoded fibres that are less prone to reading difficulties. Alignment may advantageously be used whenmultiple fibres are generated at the same time. The latter may reduce the economic and time cost for manufacturing the encoded fibres. Straight fibres and/or aligned fibres furthermore may allow encoding using a scanning laser beam for locally destroying fluorophores. Straight and or aligned fibres may be obtained by electrospinning the microfibre or nanofibre on a quickly moving receiving surface. In one embodiment, such fibres may be obtained using a conventional electrospinning dope and a rotating drum at high speed as collector. In one step, the method also comprises locally bleaching the fluorophores for generating a code. The local bleaching may be performed by photobleaching or photolysis. Spatial selective photobleaching may be performed by exposing well selected regions with radiation, e.g. laser radiation. The latter is illustrated in Figure 2D. It is an advantage of embodiments according to the present invention that it makes use of photobleaching, as this allows obtaining immobilised fluorophores in the fibres at room temperature, resulting in less disappearance of the encoding as the fluorophores are prevented from becoming mobile which would result in recovery of the fluorescence in the bleached zones. Another example of photobleaching may be illumination through a mask whereby the fibres may be encoded by fotobleaching using a source and passing the source rays at the appropriate positions of the mask, which results in providing the fibres with a unique coding. The mask may also contain holes through which a high energy ray can pass to cut the fibre into small pieces, as described in a different step.
Optionally, the fibres also may be cut into smaller pieces and the smaller pieces of fibre may be used as encoded fibres for encoding objects. Cutting of longer fibres may be performed using for example cold ablation, although the invention is not limited thereto, cutting also may be performed by templating or by razor cutting. The length of the fibres may be in the range ΙΟΟΟμιη to 50μιη, e.g. in the range 500μιη to 50μιη. By way of illustration, cutting is shown in Figure 2C.
Cutting and encoding may be performed in any suitable order, i.e. first encoding then cutting, first cutting then encoding or performing cutting and encoding simultaneously.
The method also may comprise the step of applying encoded fibres to a larger object to be encoded. The latter may for example be obtained by mixing the fibres into the object to be encoded, providing the fibres to a surface of the object to be encoded, etc. Providing the fibres to a surface of the object to be encode may for example be obtained by making a suspension of the locally bleached fibres and applying the suspension to the object. After drying the fibres may be automatically fixed to the surface of the object. In such a step the fibres thus may be brought into a liquid to form a dispersion, of which a drop is brought onto any appropriate surface (drug, packaging, ...).
Further features and advantages may be provided by optional method steps corresponding with or leading to features of the device embodiments according to the present invention.
By way of illustration, embodiments of the present invention not being limited thereto, a number of particular embodiments illustrating the first and second aspect of the present invention are given below.
In one particular embodiment, the objects encoded are oral medicines, in particular tablets or capsules containing drugs. In the embodiment, encoded fibres, such as for example encoded micron sized fibres or encoded nano sized fibres made from pharmaceutical materials, are used for encoding drugs. Fluorophores are immobilised in glassy polymer fibres, resulting in stable encoding of objects. The latter is obtained by selecting the glass transition temperature of the polymer fibre and the physicochemical interactions between the fluorophore and the polymer appropriately resulting in encoding by photobleaching that is stable over long periods. As illustrated by the example below, the encoded fibres at the tablet's surface can be easily decoded using a basic fluorescence microscope, even without removing the fibre pieces from the tablets. It is an advantage of embodiments according to the present invention that a simple and inexpensive strategy is obtained for 'digital encoding fibres'. It thereby is an advantage that the fibres can be made of those pharmaceutical ingredients having already been used for decades in tablets and other types of oral medicines. All drugs could make use of such encoding, such as for example today's "lifestyle drugs" like e.g. sexual performance enhancers, smoking cessation agents, antibiotics, painkillers, anti-malarial or HIV drugs. Similarly, such polymers also can be used for identifying authentic food, etc. It is an advantage of embodiments according to the present invention that the encoded fibres remain harmless after encoding and can be decoded using a fast detection technique, as the orientation of the orientation of the fibre and the code can be easily determined., allowing to use such methods against counterfeiting also in developing countries. In some embodiments, fast and low cost detection is obtained.
Figure imgf000016_0001
Table 1
By way of illustration, some examples of the production of encoded microfibres is discussed below. Microfibres were obtained by electrospinning polymer solutions containing a fluorophore (Table 1), using an electrospinning setup. Two arguments explain our choice for electrospinning. Firstly, it is a remarkably simple technique that allows preparing the most simple polymeric matrices from a wealth of pharmaceutical polymers. Secondly, electrospinning allows aligning the microfibres which is a requirement when encoding the fibres by a scanning laser beam that locally destroys the fluorophores. An electrospinning setup as can for example be used is shown in Figure 2A, indicating a power supply 202, one or more syringe 204 with a flat tip needle 205 and optionally a pump pressure providing means 206 and a grounded collector 208. The collector may comprise a glass support 210. Such systems are known by the person skilled in the art. A droplet of the polymer/fluorophore solution is formed at the tip of the needle by surface tension while charge is induced on the droplet surface by an electric field. When the electric field reaches a critical value at which the electric force overcomes the surface tension of the droplet, a charged jet is ejected from the tip. While the jet travels in air, the solvent evaporates, resulting in the deposition of fibres on a collector. A rotating collector 208 is used fitted with a glass support, as shown in Figure 2B to collect aligned fibres 220. Typically a motor 212 may be provided for rotating the collector 208. It is an advantage of at least some embodiments of the present invention that the fibres during electrospinning are collected on a moving surface so that aligned fibres can be generated. The fibres 220 on the glass support were dried in open air. Highly aligned polystyrene (PS), ethylcellulose (EC), cellulose-acetate-phthalate (CAP), and poly(lactic-co-glycolic acid) (PLGA)-microfibres could be obtained by rotating the wheel at high speed. As FIG 3A illustrates, the higher the rotating speed, the better the fibres were aligned. Results are shown for different relative rotation speed values, i.e. 100, 600, 900, 1200 rotations per time unit respectively, as indicated in the drawings. Appropriate solvents were used, some resulting in more stable encoding than others. Selection of solvents may depend on the polymer and dye used. Some examples of suitable combinations of polymers and solvents are shown in Table 1. In some embodiments advantageously water can be used as solvent, such as for example with the combination PEO and flurorescein. Fluorescein is a common water- soluble fluorophore. Fluorescein capsules are taken by patients to diagnose ophthalmologic diseases. The fibres were loaded with the fluorescein derivative fluoresceinisothiocyanate (FITC), which is soluble in dimethylformamide DMF and tetrahydrofuran THF used to solve PS, EC, CAP and PLGA. FIG. 3B part 1 shows that PS-fibres can be homogeneously loaded with FITC (the brighter portions indicating the fluorescent portions) though, one day after keeping the fibres in open air at room temperature, FITC seems to have significantly migrated towards the surface of the fibres, as can be seen in FIG. 3B part 2 wherein the brighter portions are now at the edges of the fibres. Furthermore, especially upon dispersion in water, FITC significantly leaks from the fibres into the water, as can be seen in FIG. 3B part 3 where the brighter portions are not or less significant present in or at the edges of the fibres. An insufficient immobilization of FITC in the PS-fibre and a too high solubility in water made FITC less suitable. An advantageous fluorophore is for example coumarin-6. As FIG. 3C shows, even after 4 days' storage in open air (FIG. 3C part 2) and after one day being dispersed in water (FIG. 3C, part 3), PS-fibres loaded with coumarin-6 remained homogeneously coloured. For comparison the fluorescence of the fibres just after manufacturing is also shown (FIG. 3c, part 1). This was not only the case for PS-fibres, coumarin-6 seemed also well suited to design stable homogeneously coloured ethylcellulose (EC), cellulose-acetate-phthalate (CAP), and poly(lactic-co-glycolic acid) (PLGA)-microfibres. FIG. 4A illustrates aligned fibres for (from left to right) polystyrene (PS), ethylcellulose (EC), poly(lactic-co- glycolic acid) (PLGA) and cellulose-acetate-phthalate (CAP) microfibres. The brighter portions are indicative of the fluorescence in the fibres. As shown in FIG. 2C, the aligned fluorescent fibres were cut into small pieces 230, by cold ablation using a control system 240, in the present example a PALM MicroBeam System Version 4.0 AxioVert laser equipped with a 355 nm pulsed UV-Laser. As shown in FIG. 4B, a scanning UV laser could cut the aligned fibres into 100-200 μιη long pieces (from left to right : polystyrene (PS), ethylcellulose (EC), poly(lactic-co-glycolic acid) (PLGA) and cellulose-acetate-phthalate (CAP) microfibres). The brighter portions are indicative of the fluorescence in the fibres. The fabrication of small fibre pieces has recently received attention and also other techniques for cutting the fibres into pieces could be used such as for example the use of templates or cutting by razor blades under liquid nitrogen into 50-100μιη rod-like pieces. The fluorescent fibre pieces were encoded with a code 250 by spatial selective photobleaching by exposing well selected regions to a 488 nm laser beam, i.e. using an encoding device 260, as shown in FIG. 2D. An in-house-developed encoding device was used, being a laser scanning confocal microscope (Nikon) equipped with an argon laser and an acousto-optic modulator. FIG. 4C shows that the coumarin-6 loaded fibre pieces could be digitally encoded by photobleaching by a laser beam scanning along the longitudinal axis of the fibre pieces (from left to right : polystyrene (PS), ethylcellulose (EC), poly(lactic- co-glycolic acid) (PLGA) and cellulose-acetate-phthalate (CAP) microfibres) according to a process as shown in FIG. 2D. The brighter spots indicate the fluorescent portions. Upon bleaching, the fluorescent molecules lose their fluorescence, giving rise to the code. The encoded fibre pieces (which also may be referred to as "memofibres'), were dispersed in water, simply by applying a drop of water on the fibre pieces on the glass support. It is advantageous to obtain a stable code. Clearly, the more mobile the fluorophore in the polymer fibres, the faster the digital code will disappear.
In order to provide detectability of the code over a reasonable lifetime of the product, the contrast should be sufficiently high. This contrast is determined by the mobility of the photobleached or unbleached fluorophores and advantageously of both the photobleached and unbleached fluorophores in the fibres, which is influenced by the particular fluorophore used in combination with the composition and structure of the fibre. At least a fraction of the photobleached or unbleached and advantageously of both the photobleached and unbleached fluorophores should be immobile or behave substantially immobile, as the contrast is in the end determined by such immobile or substantially immobile fraction. Numerical calculation techniques are known in the art for determining how the contrast will lower over time. In order to determine whether a particular combination of fluorophore and fibre composition and structure will lead to sufficient immobilised fluorophores, such numerical calculations may be performed, taking into account a diffusion coefficient as can be determined using Fluorescence Recovery After Photobleaching and optionally also taking into account the spatial distribution of the code to be induced and/or the bleaching resolution and/or the imaging resolution and/or intensity distribution of the bleaching beam used, etc. Embodiments of the present invention thus also include using numerical calculation techniques for determining whether sufficient contrast for a certain fluorophore and fibre exists. Alternatively, also long term experiments could be applied. If one assumed coumarin-6 diffusing in water, one could easily calculate from Stokes- Einstein law that it would take only seconds to travel a few micrometers. As the encoded segments are typically five to ten micrometers, sufficiently immobilizing the fluorophore in the fibres was necessary to avoid even the smallest displacement over the long term (months, years) and resulting in codes that are expected to survive. FIG. 4E shows the contrast of the codes as a function of time (for polystyrene (PS), ethylcellulose (EC), cellulose-acetate-phthalate (CAP), and poly(lactic-co-glycolic acid) (PLGA)-microfibres). Clearly, in EC-fibres the code fades away over time. Although, in PS-, CAP- and PLGA-fibres the fluorescence recovery in the bleached segments is very weak keeping the codes clearly legible after 4 months' storage. All fibres were thus in amorphous state at room temperature. Using a lactose/microcrystalline cellulose mixture 20 mm tablets were prepared. 2μΙ of a memo-fibre dispersion 270 was dripped onto the surface of the tables 280 (FIG. 2E) and subsequently dried at 37°C for 12h. For decoding, the surface of the tablets was imaged by a (non-confocal) fluorescence microscope. The codes in fibre pieces deposited at the surface of tablets could clearly be identified. FIG. 4D shows the fluorescence images (the brighter portions are indicative of the fluorescence in the fibres) we obtained from fibres at the surface of tablets using a simple fluorescence microscope (from left to right : polystyrene (PS), ethylcellulose (EC), poly(lactic-co-glycolic acid) (PLGA) and cellulose- acetate-phthalate (CAP) microfibres). The digital codes are perfectly readable. Even after subjecting the tablets to a friability test the codes remained readable indicating that shear stresses do not detach memo-fibres from the tablets. The above example illustrates some features and possibilities of some embodiments according to the present invention.
FIG. 5 shows the fluorescence images of encoded fibres that are composed entirely of substances that are on the FDA's list of inactive ingredients (FDA's Inactive Ingredient Guide, http://www.accessdata.fda.gov/scripts/cder/iig/index.cfm) as substances already used in oral dosage forms. Fluorescent microfibers are obtained by electrospinning a solution of fluorescein together with different matrix polymers (from left to right :poly(lactic-co-glycolic acid), poly-elthylene-oxide (PEO) andethylcellulose (EC)). The digital codes are obtained by spatio-selective photobleaching of the fluorescein, and are perfectly readable (the brighter portions are indicative of the fluorescence in the fibres) using a simple non-confocal fluorescence microscope The electrospinning conditions used for manufacturing the fibres shown 5 are illustrated in Table 2.
Figure imgf000021_0001
Table 2 In a second particular example, the objects are a web comprising encoded fibres. The web may be a fibre-web and may be used in a plurality of applications, such as for example in encoded textiles like for wearable clothing, software carriers, perfumes, tobacco products, medical devices, drug formulations. As an example, one can imagine the loading of such webs with different types of cells (or different types of bacteria) whereby the codes in the fibres allow to remember which type of cells (or bacteria) is present at a specific location. As another example, fibres in such a web may be loaded with different types of bioactive compounds (like e.g. each fibre loaded with another growth factor) to be locally released to cells which are supported by the web: the codes in the fibre may allow to identify to which types of drugs cells in specific areas of a web were exposed. An advantage of having a web as object comprising encoded fibres is that the web itself can be used directly in a variety of applications where identification and/or prevention of counterfeiting can be important. Materials used and techniques used for producing the web may be similar as described above, although the invention is not limited thereto. By way of illustration, an example of a web comprising encoded fibres, is shown in FIG. 6. FIG. 6 shows a polystyrene microfibre web that was obtained by electrospinning polystyrene solution containing a coumarine-6. An electrospinning setup similar as shown in FIG. 2A but having a flat collector was used. The fluorescent fibre pieces webs (while still on the glass support) were encoded by spatial selective photobleaching by exposing well selected regions to a high intensity 488 nm laser beam. An in-house-developed encoding device was used, being a laser scanning confocal microscope (Nikon Benelux, Brussels, Belgium) equipped with an Aerotech ALS3600 scanning stage, a SpectraPhysics 2060 argon laser, and an Acousto-Optic Modulator. Upon selectively bleaching, the fluorescent molecules lost their fluorescence, giving rise to the code. Different barcode could be encoded at different position of polystyrene web. The latter could for example also be used for localization of different positions in a web. The latter illustrates some possibilities and features of some embodiments of the present invention.
It is an advantage of device embodiments according to the present invention that due to the cylindrical geometry of the polymer fibres a complicated step for providing a proper orientation of the fibres is not necessary for decoding. Regardless of the position of the fibres the codes are readable.
It is an advantage of embodiments according to the present invention that due to the simple chemical composition, approval for use in foods or drugs can be more easily obtained. The size furthermore plays an important role as can be seen from the following calculation, using the example described : a 100 μιη fibre contains as little as 0.1 picogram coumarin-6. If one applies 10 fibres per encoding of a tablet of drugs and assume a patient would take 10 tablets a day, the daily intake of coumarin-6 would be around 10 picogram. Thus, even if a fluorophore is not declared safe for use in food of drugs (yet), depending on legislation it may be considered an impurity and an "impurity" in a drug formulation can, depending on legislation, be allowed as long as the daily intake remains lower than 1.5 microgram.
It is an advantage of embodiments according to the present invention that, as both the length and the thickness of memo-fibres can be easily controlled through appropriate spinning and cutting, it is possible to store information in the length as well as the diameter of the memo-fibres. Other variations to the disclosed embodiments can be understood and effected by those skilled in the art in practicing the claimed invention, from a study of the drawings, the disclosure and the appended claims. In the claims, the word "comprising" does not exclude other elements or steps, and the indefinite article "a" or "an" does not exclude a plurality. A single processor or other unit may fulfil the functions of several items recited in the claims. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage. A computer program for performing at least part of the method may be stored/distributed on a suitable medium, such as an optical storage medium or a solid-state medium supplied together with or as part of other hardware, but may also be distributed in other forms, such as via the Internet or other wired or wireless telecommunication systems. Any reference signs in the claims should not be construed as limiting the scope.
The foregoing description details certain embodiments of the invention. It will be appreciated, however, that no matter how detailed the foregoing appears in text, the invention may be practiced in many ways, and is therefore not limited to the embodiments disclosed. It should be noted that the use of particular terminology when describing certain features or aspects of the invention should not be taken to imply that the terminology is being re-defined herein to be restricted to include any specific characteristics of the features or aspects of the invention with which that terminology is associated.

Claims

Claims
1. - An encoded object, the object comprising at least one encoded fibre (230), the encoded fibre (230) being a microfibre or nanofibre comprising a polymer and a bleachable fluorophore, the fluorophore being spatially bleached so as to generate a code (250) on the fibre (220), readable by exciting the fluorophore.
2. - An encoded object according to claim 1, wherein the encoded fibre (230) is an electrospun fibre electrospun from a mixture comprising the polymer and the fluorophore .
3. - An encoded object according to any of the previous claims, wherein the
fluorophore is immobilized in the polymer matrix in the fibre (220).
4. - An encoded object according to any of the previous claims, wherein the
fluorophore is covalently bound to the polymer in the fibre (220).
5. - An encoded object according to any of the previous claims, wherein the polymer is safe for use in food or drugs.
6.- An encoded object according to any of the previous claims, wherein the
fluorophore is safe for use in food or drugs.
7.- An encoded object according to any of the previous claims, wherein the polymer is any of polystyrene, cellulose-acetate-phthalate or poly(lactic-co-glycolic acid), polyethylene glycol, ethyl cellulose, polyethylene oxide.
8.- An encoded object according to any of the previous claims, wherein the
fluorophore is coumarin-6 or fluorescein.
9.- An encoded object according to any of the previous claims, wherein the object is a drug or food and wherein the at least one encoded fibre is added to the drug or food.
10.- An encoded object according to any of the previous claims, wherein the object is a web of fibres comprising the at least one encoded fibre.
11.- A method for providing an encoded object, the method comprising
- providing at least one microfibre or nanofibre comprising a polymer and a bleachable fluorophore, - locally bleaching the fluorophore so as to generate a code on the fibre, the code being readable by exciting the fluorophore.
12. - A method according to claim 11, wherein providing a microfibre or nanofibre comprises electrospinning a microfibre or nanofibre.
13. - A method according to claim 12, wherein electrospinning at least one microfibre or nanofibre comprises electrospinning a microfibre or nanofibre on a quickly moving surface so as to obtain a susbstantially straight microfibre or nanofibre.
14. - A method according to any of claims 11 to 13, wherein locally bleaching the fluorophore comprises photobleaching the fluorophore.
15. - A method according to any of claims 11 to 14, wherein providing at least one microfibre or nanofibre comprises cutting the nanofibre or microfibre.
16. - A method according to any of claims 11 to 15, the method comprising applying a suspension of the locally bleached fibres to the object.
17. - Use of an encoded object according to any of claims 1 to 10 for preventing
counterfeit.
PCT/EP2010/070172 2009-12-18 2010-12-17 Encoded fibres WO2011073442A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB0922177.1A GB0922177D0 (en) 2009-12-18 2009-12-18 Encoded fibres
GB0922177.1 2009-12-18

Publications (1)

Publication Number Publication Date
WO2011073442A1 true WO2011073442A1 (en) 2011-06-23

Family

ID=41717206

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2010/070172 WO2011073442A1 (en) 2009-12-18 2010-12-17 Encoded fibres

Country Status (2)

Country Link
GB (1) GB0922177D0 (en)
WO (1) WO2011073442A1 (en)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015200572A1 (en) * 2014-06-27 2015-12-30 Eastman Chemical Company Fibers with physical features used for coding
WO2016149122A3 (en) * 2015-03-13 2017-01-05 Illumina, Inc. Reading and writing codes using optical devices
US9863920B2 (en) 2014-06-27 2018-01-09 Eastman Chemical Company Fibers with chemical markers and physical features used for coding
US10515256B2 (en) 2017-09-12 2019-12-24 Eastman Chemical Company Cellulose acetate tow bands and filters with surface markings

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999017486A1 (en) * 1997-09-30 1999-04-08 Tracer Detection Technology Corp. System and method for authentication of goods
US6035914A (en) * 1993-10-22 2000-03-14 Martin Marietta Energy Systems Inc. Counterfeit-resistant materials and a method and apparatus for authenticating materials
WO2002033419A1 (en) * 2000-10-19 2002-04-25 Tibotec Bvba Method and device for the manipulation of microcarriers for an identification purpose
EP1479797A1 (en) * 2003-05-22 2004-11-24 Landqart Photoluminescent fibre, security paper and other security articles
US20090136932A1 (en) * 2007-03-16 2009-05-28 Craighead Harold G Fibers with isolated biomolecules and uses thereof

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6035914A (en) * 1993-10-22 2000-03-14 Martin Marietta Energy Systems Inc. Counterfeit-resistant materials and a method and apparatus for authenticating materials
WO1999017486A1 (en) * 1997-09-30 1999-04-08 Tracer Detection Technology Corp. System and method for authentication of goods
WO2002033419A1 (en) * 2000-10-19 2002-04-25 Tibotec Bvba Method and device for the manipulation of microcarriers for an identification purpose
EP1479797A1 (en) * 2003-05-22 2004-11-24 Landqart Photoluminescent fibre, security paper and other security articles
US20090136932A1 (en) * 2007-03-16 2009-05-28 Craighead Harold G Fibers with isolated biomolecules and uses thereof

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
CHAE ET AL.: "Polydiacetylene Supramolecules in Electrospun Microfibres : Fabrication, Micropatterning, and Sensor Applications", ADVANCED MATERIALS, vol. 17, 20 July 2001 (2001-07-20), pages 521 - 524, XP002629961 *
CHAE ET AL.: "Polydiacetylene Supramolecules in Electrospun Microfibres : Fabrication, Micropatterning, and Sensor Applications", ADVANCED MATERIALS, vol. 17, 2007, pages 521 - 524
NICEWARNER-PENA S R ET AL: "SUBMICROMETER METALLIC BARCODES", SCIENCE, AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE, WASHINGTON, DC; US, vol. 294, no. 5540, 5 October 2001 (2001-10-05), pages 137 - 141, XP001128112, ISSN: 0036-8075, DOI: DOI:10.1126/SCIENCE.294.5540.137 *

Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3575488A1 (en) * 2014-06-27 2019-12-04 Eastman Chemical Company Method of making an acetate tow band comprising fibers with surface markings used for coding
CN106488712A (en) * 2014-06-27 2017-03-08 伊士曼化工公司 There is the fiber of the surface marker for coding
JP2021119270A (en) * 2014-06-27 2021-08-12 イーストマン ケミカル カンパニー Fibers with physical characteristics used for coding
US10452873B2 (en) 2014-06-27 2019-10-22 Eastman Chemical Company Fibers with surface markings used for coding
RU2692208C2 (en) * 2014-06-27 2019-06-21 Истман Кемикал Компани Fibres with identification marks on surface used for encoding
US9633579B2 (en) 2014-06-27 2017-04-25 Eastman Chemical Company Fibers with physical features used for coding
US9863920B2 (en) 2014-06-27 2018-01-09 Eastman Chemical Company Fibers with chemical markers and physical features used for coding
US9865182B2 (en) 2014-06-27 2018-01-09 Eastman Chemical Company Fibers with surface markings used for coding
US9916482B2 (en) 2014-06-27 2018-03-13 Eastman Chemical Company Fibers with physical features used for coding
US10127410B2 (en) 2014-06-27 2018-11-13 Eastman Chemical Company Fibers with physical features used for coding
US9442074B2 (en) 2014-06-27 2016-09-13 Eastman Chemical Company Fibers with surface markings used for coding
WO2015200598A1 (en) * 2014-06-27 2015-12-30 Eastman Chemical Company Fibers with surface markings used for coding
CN106488712B (en) * 2014-06-27 2020-07-03 伊士曼化工公司 Fiber with surface markings for coding
EP3161193B1 (en) * 2014-06-27 2019-10-23 Eastman Chemical Company Acetate tow band with chemical markers and physical features used for coding
US10527593B2 (en) 2014-06-27 2020-01-07 Eastman Chemical Company Method of making fibers with chemical markers and physical features used for coding
WO2015200572A1 (en) * 2014-06-27 2015-12-30 Eastman Chemical Company Fibers with physical features used for coding
EP3575453A1 (en) * 2014-06-27 2019-12-04 Eastman Chemical Company Acetate tow band comprising standard fibres and identification fibres
US10460140B2 (en) 2015-03-13 2019-10-29 Illumina, Inc. Reading and writing codes using optical devices
WO2016149122A3 (en) * 2015-03-13 2017-01-05 Illumina, Inc. Reading and writing codes using optical devices
US20180341798A1 (en) * 2015-03-13 2018-11-29 Illumina, Inc. Reading and writing codes using optical devices
US10515256B2 (en) 2017-09-12 2019-12-24 Eastman Chemical Company Cellulose acetate tow bands and filters with surface markings

Also Published As

Publication number Publication date
GB0922177D0 (en) 2010-02-03

Similar Documents

Publication Publication Date Title
Huang et al. Unbreakable codes in electrospun fibers: digitally encoded polymers to stop medicine counterfeiting
Forghani et al. Electrospun nanofibers as food freshness and time-temperature indicators: A new approach in food intelligent packaging
Destaye et al. Glutaraldehyde vapor cross-linked nanofibrous PVA mat with in situ formed silver nanoparticles
Leidy et al. Use of electrospinning technique to produce nanofibres for food industries: A perspective from regulations to characterisations
US20110263037A1 (en) Polymeric materials incorporating core-shell silica nanoparticles
Costoya et al. Electrospun fibers of cyclodextrins and poly (cyclodextrins)
Seib et al. pH‐dependent anticancer drug release from silk nanoparticles
Wang et al. Hollow polycaprolactone composite fibers for controlled magnetic responsive antifungal drug release
Yang et al. Release pattern and structural integrity of lysozyme encapsulated in core–sheath structured poly (dl-lactide) ultrafine fibers prepared by emulsion electrospinning
Smith et al. Metal nanomaterials for optical anti-counterfeit labels
Konwarh et al. Electrospun cellulose acetate nanofibers: the present status and gamut of biotechnological applications
Strozyk et al. Spatial analysis of metal–PLGA hybrid microstructures using 3D SERS imaging
Wang et al. Co‐encapsulation of biodegradable nanoparticles with silicon quantum dots and quercetin for monitored delivery
Johnston et al. Layer-by-layer engineered capsules and their applications
US20110135697A1 (en) Edible holographic silk products
WO2011073442A1 (en) Encoded fibres
JP4398368B2 (en) Multifunctional product marker, method for producing the same, and method for using the same
Khalid et al. Fluorescent nanodiamond silk fibroin spheres: advanced nanoscale bioimaging tool
TWI320064B (en)
Demir et al. Magnetic nanoparticle-loaded electrospun poly (ε-caprolactone) nanofibers for drug delivery applications
US20110111225A1 (en) Extruded Filament Having High Definition Cross-Sectional Indicia/Coding, Microscopic Tagging System Formed Therefrom and Method of Use Thereof for Anti-Counterfeiting of Product Authentication
Srivastav et al. Biomimetic hydroxyapatite a potential universal nanocarrier for cellular internalization & drug delivery
Torres-Martínez et al. Preparation and characterization of electrospun fibrous scaffolds of either PVA or PVP for fast release of sildenafil citrate
Liu et al. Aggregation-induced emission of a 2D protein supramolecular nanofilm with emergent functions
JP2008528443A (en) Microscopic tagging system for security identification

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 10796022

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 10796022

Country of ref document: EP

Kind code of ref document: A1