micromod Partikeltechnologie GmbH Products 2018

Transcription

1 micromod Partikeltechnologie GmbH s 2018

2 Modular Designed Nano and Micro Particles micromod Partikeltechnologie GmbH FriedrichBarnewitzStraße 4, D18119 Rostock Tel.: / , Fax: / Technical Support Tel.: / Internet:

3 Modern particle applications require high levels of functionality and quality with regard to substrate fixation, separation and detection. Micromod s customers are predominantly producers of diagnostic kits and highthroughput equipment, biotechnology companies, and various research institutions. Chemical surfacefunctionalized and/or magnetizable polymer particles for predominantly biochemical applications take center stage in the portfolio and the development activities. The synthetic strategies designed within the company enable particle production from milliliter to bulk scale quantities depending on application. The broad range of micro and nanoparticle products is reflected in our comprehensive catalog, which contains about 1000 items. The major line of products are nanomag (magnetic polysaccharide particles), (polystyrene copolymer particles) and (silica particles). These particle types are complemented with a variety of biodegradable particles and additional highly specialized particles such as magnetic BNFparticles (Bionized NanoFerrite), which are thermally blocked at room temperature or IDAlatex particles, which possess a very high binding capacity for trace elements. Dextran based magnetic particles of the perimag and synomag series feature excellent properties in MRI, MPI and hyperthermia applications. For the separation of nucleic acids, nanomag particles are available that combine unique surface properties with a high magnetomobility. Fluorescent and particles are of particular interest for applications in Life Sciences due to their high fluorescence intensity and variable surface chemistry. The offered particle types are available in a broad range of particle diameters and functionalizations. Selected products can be supplied according to the cgmp requirements in coordination with the customer. Most recent scientific findings in the area of particle technology are constantly embedded into the ongoing operations to develop customized solutions as a partner in cooperative projects with renowned domestic and foreign research institutions. A modern quality management according to EN ISO in combination with a sophisticated particle analysis system allows the micromod Partikeltechnologie GmbH to ensure customers a high quality standard in all product categories. I

4 overview Micromod's particle assortment comprises nanoparticles with diameters as small as 10 nm to microparticles with diameters up to 100 µm. The diagram below gives a rough overview on the ranges of magnetic, fluorescent, white and coloured particles of the different particle categories, that are exed in the table on the right. 10 nm 20 nm 100 µm dextran 80 nm bionized nanoferrite 2 1 Magnetic particles polystyrene 30 µm 100 µm 350 nm poly(lactic acid) silica 150 nm poly(ethylene imine) 150 nm chitosan nm Fluorescent particles iron oxide 25 nm 20 µm polystyrene, polymethacrylate 100 µm poly(lactic acid) albumin 300 nm dextran bionized nanoferrite 30 µm 100 µm 10 nm silica 100 µm polystyrene, polymethacrylate 100 µm poly(lactic acid) 300 nm latex albumin Colored particles poly(lactic acid) 20 µm 25 nm White particles 100 µm silica 1 10 nm II silica Fluorescent magnetic particles matrix polystyrene 100 µm poly(lactic acid) 100 µm

5 Table of s Particle property Particle matrix Contents dextran crosslinked dextran magnetic bionized nanoferrite polystyrene silica silicafortified dextran chitosan poly(lactic acid) poly(ethylene imine) iron oxide Contents nanomag D nanomag Dspio perimag synomag D nanomag CLD nanomag CLDspio BNF particles micromer M sicastar M sicastar MCT nanomag silica nanomag C PLAM PEIM Iron oxide particles silica fluorescent polystyrene, polymethacrylate poly(lactic acid) fluorescent and magnetic albumin Contents dextran bionized nanoferrite poly(lactic acid) white Contents silica polystyrene, polymethacrylate poly(lactic acid) latex albumin Contents sicastar greenf sicastar redf sicastar bluef micromer greenf micromer redf PLAgreenF PLAredF AlbumingreenF nanomag CLDredF BNFredF PLAMredF PLAMgreenF sicastar micromer PLA particles IDALatex particles Albumin particles colored silica polystyrene poly(lactic acid) sicastar black red blue micromer blue PLAblue Page III

6 Special services Development and production of customized particles types Customized filling of products design of custom particles Particle production under controlled hygienic conditions Coupling of antibodies, peptides, oligonucleotides and other molecules Size determination of particles Zeta potential measurement of particles Determination of AC susceptibility of magnetic particles Drying of particles on request Research samples and prototypes on request IV

7 Magnetic particles page nanomag D 2 Plain and PEGylated particles 2 Functionalized particles 3 Protein coated particles 4 Particles with chelators for metal ions on the surface 4 nanomag Dspio 5 Plain and functionalized particles 5 Protein coated particles 7 perimag 8 synomag D 9 nanomag CLD 10 nanomag CLDspio 11 BNF particles 12 Plain and functionalized particles 12 Protein coated particles 13 M 14 Functionalized particles 14 Protein coated particles 16 M 17 Plain and functionalized particles 17 Protein coated particles 18 MCT 19 Plain and functionalized particles 19 Protein coated particles 20 nanomag silica 21 nanomag C 22 PLAM particles 23 PEIM particles 24 Iron oxide particles 24 1

8 nanomag D nanomag D particles are prepared via the coreshell method with a core of magnetite and a dextran shell. The magnetite core consists of aggregates of individual iron oxide crystals with diameters of 515 nm. nanomag D particles contain 7580% (w/w) magnetite in a matrix of dextran (MW: D) and can easily be separated with a conventional permanent magnet. The nanomag D particles are available with particle diameters of 130 nm, and. TEM image of nanomag D particles, (section) Magnetic dextran nanoparticles (nanomag D) are designed with the surface functionalities OH (), and for the covalent binding of proteins, antibodies or other molecules, are available with covalently bound proteins (,, protein A, albumin) or other biomolecules (biotin, glutathion), can be provided with covalently bound antibodies on request, are offered with the nickel(ii) chelator nitrilotriacetic acid (NTA) or ready to use with the corresponding nickel complex (NiNTA) for the binding of histidine labeled proteins, are available with various hydrophilic surfaces (PEG 300, PEGNH 2 or PEG), are available with negative surface potentials (e.g., SO3H). magnetic particles Plain and PEGylated particles Plain nanomag D particles have an unmodified dextran surface. They have a high potential for nucleic acid separation. Especially the nanomag D particles provide an excellent magnetic mobility in highthroughput nucleic acid separations. The surface modification with PEG 300 prevents the unspecific protein binding on the particle surface. nanomag D particles are supplied in water without any surfactants nanomag D 130 nm nanomag D nanomag D nanomag D PEG nm nanomag D PEG 300

9 nanomag D Functionalized particles nanomag D particles with diameters of 130 nm, and are designed with the surface functionalities, or the corresponding more hydrophilic PEGNH 2 or PEG groups for the covalent binding of proteins, antibodies or other molecules. Thus several conjugation methods can be applied, e.g. carbodiimide activation of groups for conjugation to amino groups, glutaraldehyde activation of amino groups for conjugation to amino groups or maleimide or SPDP functionalization of the amino groups for conjugation of SHlabeled biomolecules. Furthermore 130 nm and nanomag D particles are available with SO3H groups to provide a negatively charged surface, and with biotin to allow the specific binding of or or their conjugates. The nanomag D particles with glutathion on the surface can be used for affinity purification of glutathionestransferase (GST) and GST fusion proteins from cell lysates of various kinds. Upon incubation of a sample with the glutathione particles, GSTtagged proteins bind to the immobilized glutathione ligand, allowing undesired components of the sample to be washing away by magnetic separation. Addition of reduced glutathione or an acid buffer recovers the GST fusion protein in purified form. All functionalized nanomag D particles are supplied in water without any surfactants nanomag D 130 nm nanomag D nanomag D nanomag D 130 nm nanomag D nanomag D nanomag D SO3H 130 nm nanomag D SO3H nanomag D biotin 130 nm nanomag D biotin nanomag D biotin nanomag D PEG 130 nm nanomag D PEG nanomag D PEG nanomag D PEG 130 nm nanomag D PEG nanomag D PEG nanomag D glutathione 130 nm nanomag D glutathione magnetic particles 3

10 nanomag D Protein coated particles nanomag D particles with diameters of 130 nm, and are provided with covalently bound proteins (,, protein A, albumin). The protein coated particles are supplied in PBS buffer (ph=7.4) with 0.02 % sodium azide. Avidin and bind biotinylated molecules easily and with a high affinity, while protein A picks up and orients IgGs from a mixture of species. The particles allow an easy magnetic separation of the target molecules with permanent magnets. The nanomag D particles can be provided with covalently bound antibodies on request nanomag D 130 nm nanomag D nanomag D nanomag D 130 nm nanomag D nanomag D nanomag D 130 nm nanomag D nanomag D nanomag D albumin (BSA) 130 nm nanomag D albumin (BSA) nanomag D albumin (BSA) magnetic particles Particles with chelators for metal ions on the surface nanomag D particles with diameters of 130 nm and are offered with the nickel(ii) chelator nitrilotriacetic acid (NTA) for the binding of histidine labeled proteins. Recombinant proteins containing a 6xhistidinetag can be purified by NiNTA (nickelnitrilotriacetic acid) chromatography which is based on the interaction between a transition Ni2+ ion immobilized on a matrix and the histidine side chains. Following washing of the matrix by separation with a permanent magnet the 6xhistidinetag fusion proteins can be eluted by adding free imidazole or EDTA or by reducing the ph nanomag D NTA 130 nm nanomag D NTA nanomag D NiNTA 130 nm nanomag D NiNTA

11 nanomag Dspio nanomag Dspio particles are prepared by precipitation of iron oxide in the presence of dextran. They are available with particle diameters of 20 nm, 50 nm and. The functionalized nanomag D spio consist of about 5585% (w/w) iron oxide in a matrix of dextran (MW: Da) in dependence on the diameter and surface modification. The nanomag Dspio particles differ in the size of the iron oxide domains for different diameters. While 20 nm nanomag Dspio particles contain iron oxide crystals of 710 nm, the iron oxide crystallite diameter of the nanomag Dspio particles is 1013 nm. TEM image of nanomag Dspio particles, (section) The nanomag Dspio particles cannot be separated with a conventional permanent magnet but in a high gradient magnetic field. They are preferably applied for detection purposes in magnetic resonance imaging or in magnetoimmuno assays. sized nanomag Dspio particles show good specific power absorption rates for hyperthermia applications. Superparamagnetic dextran nanoparticles (nanomag Dspio) are designed with the surface functionalities OH (), and for the covalent binding of proteins, antibodies or other molecules, and are available with various hydrophilic surfaces (PEG 300, PEGNH 2 or PEG). Plain and functionalized particles Plain nanomag Dspio particles have an unmodified dextran surface and are available with diameters of 20 nm, 50 nm and. nanomag Dspio particles are designed with the surface functionalities OH (), and as well as PEG and PEG for the covalent binding of proteins, antibodies or other molecules. They are supplied in water with an iron concentration of about 2.4 mg/ml without any surfactants. Thus several conjugation methods can be applied, e.g. cyanogen bromide activation of particles for conjugation to amino groups carbodiimide activation of groups for conjugation to amino groups 5 magnetic particles are available with covalently bound proteins (,, protein A, albumin) or other biomolecules (e.g. biotin),

12 nanomag Dspio glutaraldehyde activation of amino groups for conjugation to amino groups or maleimide or SPDP functionalization of the amino groups for conjugation of SHlabeled biomolecules. magnetic particles MR images of 20 nm nanomag Dspio particles (spio) in rat lymph node: a) T2weighted image of spio particles in rat lymph node (right paw), b) susceptibility effects of spio particles with T2* gradient echo image, c) T1weighted image of spio in rat lymph node, d) T2 map of spio, e) T2*map of spio and, f) T1 map of spio (Firouznia K et al., Pak. J. Biol. Sci. 2008;11(4):607612) 6

13 nanomag Dspio nanomag Dspio 20 nm nanomag Dspio 50 nm nanomag Dspio nanomag Dspio 20 nm nanomag Dspio 50 nm nanomag Dspio nanomag Dspio 20 nm nanomag Dspio 50 nm nanomag Dspio nanomag Dspio biotin 20 nm nanomag Dspio biotin 50 nm nanomag Dspio biotin nanomag Dspio PEG 20 nm nanomag Dspio PEG 50 nm nanomag Dspio PEG nanomag Dspio PEG 20 nm nanomag Dspio PEG 50 nm nanomag Dspio PEG Protein coated particles nanomag Dspio particles are available with covalently bound proteins (,, protein A, albumin) or other biomolecules (e. g. biotin). The protein coated particles are supplied in PBS buffer (ph=7.4) with 0.02 % sodium azide. The iron concentration of the suspensions is about 2.4 mg/ml nanomag Dspio 20 nm nanomag Dspio 50 nm nanomag Dspio nanomag Dspio 20 nm nanomag Dspio 50 nm nanomag Dspio nanomag Dspio 20 nm nanomag Dspio 50 nm nanomag Dspio nanomag Dspio albumin (BSA) 20 nm nanomag Dspio albumin (BSA) 50 nm nanomag Dspio albumin (BSA) magnetic particles 7

14 perimag perimag particles are prepared by precipitation of iron oxide in the presence of dextran. The particles consist of about 50% (w/w) iron oxide in a matrix of dextran (MW: Da) and can be produced under clean room conditions on request. Functionalized perimag particles consist of about 70% (w/w) iron oxide in a matrix of crosslinked dextran. perimag are available with a hydrodynamic diameter of 130 nm. TEM image of perimag particles, 130 nm (section) perimag nanoparticles are available with the surface functionalities OH () and for the covalent binding of biomolecules, e.g. antibodies, peptides or oligonucleotides, are provided with covalently bound (Conjugations of other proteins or antibodies are offered on request.) Plain perimag nanoparticles have an unmodified dextran surface. They show excellent properties as contrast agent in Magnetic Particle Imaging (MPI) and Magnetic Resonance Imaging (MRI) as well as in hyperthermia applications. The particles are supplied with an iron concentration of 8. in water without any surfactants. They can be produced with higher iron concentrations and under clean room conditions on request. magnetic particles perimag with amino groups on the surface possess a moderate positive zeta potential in the physiological ph range and are interesting tools for the magnetic labeling of stem cells without use of any transfection agents. This allows the tracking and homing of stem cells in the field of regenerative medicine. The amino functionalized particles are supplied with an iron concentration of in water without any surfactants. perimag with on the surface are suitable for the binding of biotinylated molecules (e.g. antibodies, oligonucleotides, dyes). They are supplied with an iron concentration of 2.5 mg/ml in PBS buffer (ph=7.4) with 0.02% sodium azide. Other conjugations with proteins or antibodies are available on request perimag nm perimag 130 nm perimag 130 nm

15 synomag D synomag D particles are coreshell particles with a nanoflower shaped iron oxide core covered by a dextran shell. They exhibit excellent properties as tracer for Magnetic Particle Imaging (MPI) and are suitable for hyperthermia applications. The particles consist of about 55% (w/w) iron oxide (mainly gfe2o3) in a matrix of dextran (MW: Da). Functionalized synomag D particles consist of about 80% (w/w) iron oxide in a matrix of crosslinked dextran. Synomag D are available with a hydrodynamic diameter of 50 nm. TEM image of synomag D particles, 50 nm (section) synomag D nanoparticles are available with the surface functionalities OH () and for the covalent binding of biomolecules, e.g. antibodies, peptides or oligonucleotides are provided with covalently bound (Conjugations of other proteins or antibodies are offered on request.) cannot be separated with a conventional permanent magnet but in a high gradient magnetic field. Plain synomag D nanoparticles have an unmodified dextran surface and are supplied with an iron concentration of in water without any surfactants. They can be produced with higher iron concentrations on request. synomag D with on the surface are suitable for the binding of biotinylated molecules (e.g. antibodies, oligonucleotides, dyes). They are supplied with an iron concentration of 6 mg/ml in PBS buffer (ph=7.4) with 0.02% sodium azide. Other conjugations with proteins or antibodies are available on request synomag D nm synomag D 50 nm synomag D 50 nm 9 magnetic particles synomag D with amino groups on the surface are a universal platform for the direct reaction with Nhydroxysuccinimidyl ester functionalized crosslinkers or fluorescent dyes. This allows the introduction of a broad variety of surface functionalities for the desired conjugation reactions. The amino functionalized particles are supplied with an iron concentration of 6 mg/ml in water without any surfactants.

16 nanomag CLD nanomag CLD particles are prepared via the coreshell method with a core of magnetite and a dextran shell with particle diameters of 300 nm and. The particles consist of 8090% (w/w) magnetite in a matrix of crosslinked dextran (MW: D) and can easily be separated with a conventional permanent magnet. The surface of crosslinked dextran provides a high stability of the particle shell, that is especially important after binding of target molecules. The nanomag CLD particles are designed with, or PEG groups for the covalent binding of proteins, antibodies or other molecules. All functionalized nanomag CLD particles are supplied in water. The nanomag CLD particles are available with covalently bound for the binding of biotinylated target molecules. Other protein surfaces are available on request nanomag CLD 300 nm nanomag CLD nanomag CLD 300 nm nanomag CLD nanomag CLD 300 nm nanomag CLD nanomag CLD PEG 300 nm nanomag CLD PEG magnetic particles 10

17 nanomag CLDspio nanomag CLDspio p,articles are prepared by precipitation of iron oxide in the presence of dextran and subsequent crosslinking. They are available with particle diameters of 20 nm, 50 nm and and consist of about 7090% (w/w) iron oxide in a matrix of crosslinked dextran (MW: Da). Like the corresponding noncrosslinked particles they differ in the size of the iron oxide domains for different diameters. They cannot be separated with a conventional permanent magnet but in a high gradient magnetic field. The nanomag CLDspio particles are preferably applied for detection purposes in targeted magnetic resonance imaging or in magnetoimmuno assays. A very efficient conjugation of proteins and antibodies is achieved by reaction of maleimide functionalized nanomag CLDspio particles with thiolated target molecules. A technote for the introduction of maleimide groups on the surface of aminated nanomag CLDspio particles is provided at. The aminated nanomag CLDspio particles are supplied in water with an iron concentration of 2.4 mg/ml.nanomag CLDspio particles are also available with a hydrophilic PEG 300 surface. The nanomag CLDspio particles can be provided with covalently bound antibodies on request. a b c nanomag CLDspio 20 nm nanomag CLDspio 50 nm nanomag CLDspio nanomag CLDspio PEG nm nanomag CLDspio PEG nm nanomag CLDspio PEG 300 magnetic particles C595antibody conjugated 20 nm nanomag CLDspio as potential MR contract agent for ovarian cancer detection. MR image of mice: a) before injection of nanoparticles, b) after injection of 20 nm nanomag CLDspio particles and c) after injection of corresponding C595antibody labeled particles (ShabaziGahrouei D et al., J. Med. Phys. 2013;38(4):198204) 11

18 BNF particles BNF particles (Bionized NanoFerrite) are thermally blocked at room temperature and show specific interaction with alternating magnetic fields. Therefore they are an interesting tool for magnetic energy transfer and magnetic labeling. The BNF particles are prepared via the coreshell method with a core of 7580% (w/w) magnetite and a shell of dextran or hydroxyethyl starch. The magnetite crystallite diameter is about 20 nm. TEM image of BNF starch particles, (section) The BNFDextran and BNFStarch particles are available with particle diameters of 80 nm and 100 nm. The BNF particles can be separated with conventional permanent magnets, but the corresponding 80 nm particles have to be separated in high gradient magnetic fields or for several hours with strong permanent magnets. Bionized NanoFerrite particles (BNFDextran and BNFStarch) are designed with the surface functionalities OH (),, PEG, and PEG for the covalent binding of proteins, antibodies or other molecules, are available with covalently bound proteins (, protein A), can be provided with covalently bound antibodies on request, magnetic particles can easily be filtered through 0.2 filters. Plain and functionalized particles The BNF particles have a shell of dextran or hydroxyethyl starch. The corresponding functionalized BNF particles consist of a matrix of crosslinked dextran or hydroxyethyl starch, respectively. The BNFDextran and BNFStarch particles are designed with the surface groups,, PEG and PEG for the covalent binding of proteins, antibodies or other molecules. The functionalized BNF particles are supplied in water. A technote for the introduction of maleimide groups on the surface of aminated BNF particles is provided at. 12

19 BNF particles BNFStarch 80 nm BNFStarch BNFStarch 80 nm BNFStarch BNFStarch 80 nm BNFStarch BNFStarch PEG 80 nm BNFStarch PEG BNFStarch PEG 80 nm BNFStarch PEG BNFDextran 80 nm BNFDextran BNFDextran 80 nm BNFDextran BNFDextran 80 nm BNFDextran BNFDextran PEG 80 nm BNFDextran PEG BNFDextran PEG 80 nm BNFDextran PEG Protein coated particles BNF particles are available with covalently bound or protein A and can be provided with covalently bound antibodies on request. The protein coated particles are supplied in PBS buffer (ph=7.4) with 0.02 % sodium azide. The biotin binding capacity of the coated particles is about > 200 pmol/mg Fe BNFStarch 80 nm BNFStarch BNFStarch 80 nm BNFStarch BNFDextran 80 nm BNFDextran BNFDextran 80 nm BNFDextran magnetic particles BNF particles with a polydlysine (PDL) or polyllysine (PLL) coating can be applied for a direct particle loading into cells in PBS buffer (ph=7.4) without any stabilizers. A technote for the PDL or PLL coating of BNF particles is provided at. 13

20 M M are uniform microspheres consisting of magnetite around an organic matrix of a styrenemaleic acidcopolymer. The final coating with a polymer layer leads to the encapsulation of magnetite and the introduction of chemical functionalities. The M particles can easily be separated with conventional permanent magnets. They are provided in the size range of 2 to 12 microns. REM image of M particles,, Magnetic polystyrene particles (M) are designed with the surface functionalities, PEG, and PEG for the covalent binding of proteins, antibodies or other molecules, are available with covalently bound proteins (,, protein A, albumin) or other polymers (polyethylene imine). Functionalized particles M particles are designed with the surface functionalities, PEG, and PEG for the covalent binding of proteins, antibodies or other target molecules. The particles are stable in aqueous media and to some extend in DMSO. Thus the whole variety of conjugation methods can be applied, e.g. carbodiimide activation of groups for conjugation to amino groups, glutaraldehyde activation of amino groups for conjugation to amino groups or magnetic particles maleimide or SPDP functionalization of the amino groups for conjugation of SHlabeled biomolecules. M particles with a polyethylene imine (PEI) coating are designed for binding of nucleic acids or oligonucleotides. All functionalized M particles are supplied in water. 14

21 M M M M 4 µm M M M 7 µm M 8 µm M M M M 4 µm M M M 7 µm M 8 µm M M PEG M PEG M PEG 4 µm M PEG M PEG M PEG 7 µm M PEG 8 µm M PEG M PEG M PEG M PEG 4 µm M PEG M PEG M PEG 7 µm M PEG 8 µm M PEG M PEI M PEI M PEI 4 µm M PEI M PEI 8 µm M PEI magnetic particles 15

22 M Protein coated particles magnetic particles M particles are available with covalently bound proteins (,, protein A, albumin) in the size range of to 1. Avidin and bind biotinylated molecules easily and with a high affinity, while protein A picks up and orients IgGs from a mixture of species. The albumin (BSA) coating makes the surface of the polystyrene particles more hydrophilic and biocompatible if needed. The protein coated particles are supplied in PBS buffer (ph=7.4) with 0.02 % sodium azide. M particles were widely used in the development of biosensors and corresponding immunoassays M M M 4 µm M M M 7 µm M 8 µm M M M M 4 µm M M M 7 µm M 8 µm M M M M 4 µm M M M 7 µm M 8 µm M M albumin (BSA) M albumin (BSA) M albumin (BSA) 4 µm M albumin (BSA) M albumin (BSA) M albumin (BSA) 7 µm M albumin (BSA) 8 µm M albumin (BSA) 16

23 M M particles are produced by hydrolysis of orthosilicates in the presence of magnetite. M particles are available with a diameter of 350 nm or 1., respectively. These particles are not ideally spherical, but have monomodal size distributions. They can easily be separated with conventional permanent magnets and are extremely stable in organic solvents and at high temperatures. Magnetic silica particles (M) have a hydrophilic surface with terminal SiOHbonds () are designed with the surface functionalities,, Nhydroxysuccinimide (NHS) and epoxy for the covalent binding of proteins, antibodies or other molecules, are available with covalently bound proteins (,, protein A, albumin) and biotin, can be offered with the nickel(ii) chelator nitrilotriacetic acid (NTA) or ready to use with the corresponding nickel complex (NiNTA) for the binding of histidine labeled proteins, are available with a hydrophobic octadecyl (C18) surface, are deliverable with an organic polymer shell (coreshell method) on request. Plain particles and functionalized particles The 350 nm M particles have an extremely dense coating around the iron oxide core. Thus these particles are inert in many biological assays and do not influence any background signals. M particles with a diameter of 1. are available with the surface functionalities,, Nhydroxysuccinimide (NHS) and epoxy for the covalent binding of proteins, antibodies or other molecules. The particles are stable in aqueous media and also in organic solvents. This allows the conjugation of watersoluble target molecules, as well as compounds that are only soluble in organic solvents. Biotinylated M particles are also available for the selective binding of or conjugated target molecules. NHS and epoxyfunctionalized particles are provided as powder to preserve their reactivity. All other functionalized particles are supplied in water. 17 magnetic particles The 1. M particles can be used to isolate plasmiddna. 510 μg plasmid DNA per mg particles can be isolated from 11. overnight bacteria culture with OD (260 nm) / OD (280 nm) > 1.9.

24 M magnetic particles M particles with a diameter of 1. are offered with the nickel(ii) chelator nitrilotriacetic acid (NTA) or ready to use with the corresponding nickel complex (NiNTA) for the binding of histidine labeled proteins. Recombinant proteins containing a 6xhistidinetag can be purified by NiNTA (nickelnitrilotriacetic acid) chromatography which is based on the interaction between a transition Ni2+ ion immobilized on a matrix and the histidine side chains. Following washing of the matrix 6xhistidinetag fusion proteins can be eluted by adding free imidazole or EDTA or by reducing the ph. M particles with a diameter of 1. are available with a hydrophobic octadecyl (C18) surface as powder to allow a direct use in aqueous or organic solvents. This hydrophobic surface provides a high selectivity for polar, neutral and moderately nonpolar pharmaceuticals, natural products, food additives, organic chemicals and biologicals M 350 nm M 1, M 1, M 1, M epoxy 1, M NTA 1, M NHS 1, M biotin 1, M NiNTA 1, M C18 1, Protein coated particles M particles with a diameter of 1. are provided with covalently bound proteins (,, protein A, albumin). Avidin and bind biotinylated molecules easily and with a high affinity, while protein A picks up and orients IgGs from a mixture of species. The albumin (BSA) coating makes the surface of the silica particles more biocompatible if needed. The protein coated particles are supplied in PBS buffer (ph=7.4) with 0.02 % sodium azide M 1, M 1, M 1, M albumin (BSA) 1,

25 MCT M CT particles are produced by hydrolysis of orthosilicates in the presence of magnetite. They consist of clustertyped aggregates in a broad size range with a mean diameter of 6 microns. The M CT particles show a homogeneous distribution of magnetite in the silica matrix by the special preparation method and have a hydrophilic surface with terminal SiOH moieties. They can easily be separated even in highly viscous media with conventional permanent magnets and are extremely stable in organic solvents and at high temperatures. Clustertyped magnetic silica particles (MCT): are designed with the surface functionalities OH (),, and epoxy for the covalent binding of proteins, antibodies or other molecules, are available with covalently bound proteins (,, protein A, albumin), can be offered with the nickel(ii) chelator nitrilotriacetic acid (NTA) or ready to use with the corresponding nickel complex (NiNTA) for the binding of histidine labeled proteins, are available with a hydrophobic octadecyl (C18) surface. Plain and functionalized particles The MCT particles can be used to isolate plasmidedna also from highly viscous media. MCT particles are available with the surface functionalities, and epoxy for the covalent binding of proteins, antibodies or other molecules. The particles are stable in aqueous media and also in organic solvents. Beside the conjugation of water soluble molecules the conjugation of target molecules, that are only soluble in organic solvents is also possible. The and functionalized particles are supplied in water, while the epoxymodified particles are provided as powder to preserve the reactivity. A hydrophobic octadecyl (C18) surface of MCT particles provides a high selectivity for polar, neutral and moderately nonpolar pharmaceuticals, natural products, food additives, organic chemicals and biologicals. These hydrophobic particles are supplied as powder for the direct use in aqueous or organic media MCT MCT MCT MCT epoxy MCT NTA MCT NiNTA MCT C18 19 magnetic particles MCT particles can be offered with the nickel(ii) chelator nitrilotriacetic acid (NTA) or ready to use with the corresponding nickel complex (NiNTA) for the binding of histidine labeled proteins. All functionalized MCT particles are supplied in water.

26 MCT Protein coated particles MCT particles are provided with covalently bound proteins (,, protein A, albumin). Avidin and bind biotinylated molecules easily and with a high affinity, while protein A picks up and orients IgGs from a mixture of species. The albumin (BSA) coating makes the surface of the silica particles more biocompatible if needed. The protein coated particles are supplied in PBS buffer (ph=7.4) with 0.02 % sodium azide MCT MCT MCT MCT albumin (BSA) magnetic particles 20

27 nanomag silica nanomag silica particles are prepared via the coreshell method with a core of magnetite and a dextran shell with a simultaneous crosslinking of the dextran strands by silica nanostructures. They possess a diameter of and a magnetite of 7580%. nanomag silica particles can easily be separated with a conventional permanent magnet. The surface functionalities and are designed for the covalent binding of proteins, antibodies or other molecules. The nanomag silica particles with a or the hydrophobic octadecyl (C18) surface are especially interesting for highthroughput nucleic acid separation. All nanomag silica particles are supplied in water nanomag silica nanomag silica nanomag silica nanomag silica C18 O O Glycerol dextran ethers dextran strands OH O Si(OEt)3 HO OH HO O Si(OEt)3 O Si(OEt)3 O Si(EtO)4 Si OH O Si O O O Si O O Si O Si OH HO O SiO2 magnetic particles OH Intercalation of nanoscaled silica for crosslinking of the dextran strands on the surface of nanomag silica particles (Grüttner C, Teller J, J. Magn. Magn. Mat. 1999;194(4):815) 21

28 nanomag C nanomag C particles are prepared via the coreshell method with a core of magnetite and a chitosan shell. The particles have a diameter of 150 nm and a magnetite of 7580%. They can easily be separated with a conventional permanent magnet. nanomag C particles have already amino functionalities resulting from the chitosan structure without any further surface modifications (surface: ) nanomag C magnetic particles nm

29 PLAM particles PLAM particles consist of magnetite (40% w/w) in a matrix of poly(d,llactic acid) with a molecular weight of D. They are available with mean diameters of 30 µm and 100 µm. Magnetic poly(lactic acid) particles are established in the field of magnetic drug targeting in connection with a controlled drug release (The halflife time of the beads under invivo conditions mainly depends on the molecular weight of the polymers and increases with the molecular weight of the polymer.). PLAM particles can also be offered with carboxylic acid or amino groups on the surface PLAM PLAM 30 µm 100 µm PLAM µm PLAM 100 µm PLAM 30 µm PLAM 100 µm magnetic particles 23

30 PEIM particles, Iron oxide particles Magnetic poly(ethylene imine) (PEI) particles are prepared via the coreshell method with a core of magnetite and a poly(ethylene imine) shell. They have a diameter of 150 nm and a magnetite of 7580%. The magnetic PEI particles can easily be separated with a conventional permanent magnet and are interesting tools for magnetic driven transfection of cells PEIM 150 nm Iron oxide particles are available with hydrodynamic diameters of 50 nm and, respectively. The surface of the 50 nm particles is colloidal stabilized with carboxylic acid groups. The particles possess nearly no sedimentation tendency and cannot be separated with conventional permanent magnets. For magnetic separation a high gradient magnetic system is recommended. magnetic particles The iron oxide particles consist of monodisperse magnetite aggregates and can easily be separated with permanent magnets. They possess a low tendency of sedimentation and are also available with gold labeling Iron oxide particles Iron oxide particles Iron oxide particles Aulabeled nm

31 Fluorescent particles page F 26 greenf 27 redf 28 bluef 29 F 30 greenf 30 redf 31 PLAF particles 32 Albumin F particles 33 25

32 F F particles are produced by hydrolysis of orthosilicates and related compounds. They contain a high amount of covalently bound fluorescence dye in the silica matrix and are extremely stable in organic solvents and buffers. No toxic effects come from the covalently bound fluorescence dyes. They are monodisperse and nonporous in the size range of 10 nm to 1. with a density of 2.0 g/cm³ and a polydispersity index < 0.2. The larger porous sicastar F particles have broader size distributions in the area of the porous silica particles with adjusted diameters between 3 and 20 µm and a density of 1.8 g/cm³. Fluorescent silica particles (F) are available with red fluorescence (redf, excitation: 569 nm, emission: 585 nm), green fluorescence (greenf, excitation: 485 nm, emission: 510 nm) and blue fluorescence (bluef, excitation: 354 nm, emission: 450 nm), have a hydrophilic surface with terminal SiOHbonds (), are designed with the surface functionalities and for the covalent binding of proteins, antibodies, oligonucleotides, enzymes or other molecules, are available with red fluorescence and a strong hydrophobic trimethylsilyl (TMS) surface in the size range of 50 nm to 20 µm fluorescent particles are often applied for detection purposes (flow cytometry, membrane checks, flow investigations). Uptake of redf, particles in human mesenchymal stem cells (Golgi apparatus green coloured) Uptake of 50 nm carboxylated redf particles in human mesenchymal stem cells (Mitochondria green coloured) Silica particles 200 nm can easily be separated by simple sedimentation or centrifugation. particles < 200 nm can be washed by SEC (size exclusion chromatography) or ultrafiltration/dialysis or can be separated by ultracentrifugation. Silica particles with special fluorescent properties are available on request. The particles are delivered in aqueous suspension without any surfactants. 26

33 F greenf greenf particles are available in the size range of 30 nm to 20 µm with green fluorescence with an excitation at 485 nm and an emission at 510 nm greenf 30 nm greenf 50 nm greenf 70 nm greenf greenf 200 nm greenf 300 nm greenf greenf greenf 1, greenf greenf greenf greenf greenf 20 µm greenf 30 nm greenf 50 nm greenf 70 nm greenf greenf 200 nm greenf 300 nm greenf greenf greenf 1, greenf greenf 4 µm greenf greenf greenf greenf 20 µm greenf 30 nm greenf 50 nm greenf 70 nm greenf greenf 200 nm greenf 300 nm greenf greenf greenf 1, greenf greenf 4 µm greenf greenf greenf greenf 20 µm fluorescent particles 27

34 F redf fluorescent particles redf particles are available in the size range from 10 nm to 20 µm with red fluorescence with an excitation at 569 nm and an emission at 585 nm redf 10 nm redf 30 nm redf 50 nm redf 70 nm redf redf 200 nm redf 300 nm redf redf redf 1, redf redf redf redf redf 20 µm redf 30 nm redf 50 nm redf 70 nm redf redf 200 nm redf 300 nm redf redf redf 1, redf redf 4 µm redf redf redf redf 20 µm redf 30 nm redf 50 nm redf 70 nm redf redf 200 nm redf 300 nm redf redf redf 1, redf redf 4 µm redf redf redf redf 20 µm 28

35 F redf particles are also available with a strong hydrophobic trimethylsilyl (TMS) surface in the size range of 50 nm to 20 µm. These hydrophobic particles are provided as powders that allow a direct suspension of the particles in organic solvents redf redf TMS 50 nm TMS redf TMS 200 nm redf TMS 300 nm redf TMS redf TMS redf TMS 1, redf TMS redf TMS redf TMS redf TMS 20 µm bluef bluef particles are available in the size range from 70 nm to 20 µm with blue fluorescence with an excitation at 354 nm and an emission at 450 nm bluef 70 nm bluef 200 nm bluef 300 nm bluef bluef bluef 200 nm bluef 300 nm bluef bluef bluef bluef 4 µm bluef bluef bluef bluef 20 µm bluef 200 nm bluef 300 nm bluef bluef bluef bluef 4 µm bluef bluef bluef bluef 20 µm fluorescent particles 29

36 F F are monodisperse particles from polystyrene, substituted polystyrenes, polystyrenecopolymers or polymethacrylates. While the 25 nm particles consist of polymethacrylate, the larger particles have a polystyrene matrix. Plain fluorescent polystyrene / polymethacrylate particles (F) have no additional coatings or special functional groups on the surface. Fluorescent polystyrene / polymethacrylate particles are designed with carboxylic acid groups () and amino groups (NH 2) on the particle surface for the covalent binding of proteins, antibodies or other molecules, are available with red (redf, excitation: 552 nm, emission: 580 nm) and green (greenf, excitation: 475 nm, emission: 510 nm) fluorescence. The labeling with other fluorescence dyes is possible on request. F particles are supplied in aqueous suspension without any surfactants. greenf fluorescent particles greenf particles are available with an encapsulated fluorescein derivative in aqueous suspension without any surfactants. The particles are provided with diameters of 25 nm, 50 nm, and with an excitation at 475 nm and an emission at 510 nm greenf 25 nm greenf 50 nm greenf greenf greenf 25 nm greenf greenf greenf 25 nm greenf 50 nm greenf greenf 30

37 F redf redf particles are available with an encapsulated rhodamine derivative in aqueous suspension without any surfactants. The particles are provided in the nanoscale with diameters of 25 nm, 50 nm,, and in the micronscale with, 4 µm, and with an excitation at 552 nm and an emission at 580 nm. Immunofluorescence staining of A431 cells after treatment with EG2conjugated 25 nm redf particles (EGFRgreen, E2conjugated particles red, cell nucleusblue) (Witecy S, PhD thesis, HelmholtzZentrum DresdenRossendorf, 2012) redf 25 nm redf 50 nm redf redf redf 25 nm redf redf redf 25 nm redf 50 nm redf redf redf redf 4 µm redf redf fluorescent particles 31

38 PLAF particles The fluorescent poly(lactic acid) particles consist of poly(d,llactic acid) with a molecular weight of Da. They are available with diameters of and in small size distributions and with mean diameters of, 30 µm and 100 µm in broader size distributions. Plain fluorescent poly(lactic acid) particles do not have any functional groups on the surface. Fluorescent poly(lactic acid) particles are designed with carboxylic acid groups () and amino groups (NH 2) on the particle surface for the covalent binding of proteins, antibodies or other molecules, are available with red (PLAredF, excitation: 552 nm, emission: 580 nm) and green (PLAgreenF, excitation: 502 nm, emission: 527 nm) fluorescence. fluorescent particles The fluorescent poly(lactic acid) particles are supplied in water and can be loaded with drugs on request PLAgreenF PLAgreenF PLAgreenF PLAgreenF 30 µm PLAgreenF 100 µm PLAgreenF PLAgreenF PLAgreenF PLAgreenF 30 µm PLAgreenF 100 µm PLAgreenF PLAgreenF PLAgreenF PLAgreenF 30 µm PLAgreenF 100 µm PLAredF PLAredF PLAredF PLAredF 30 µm PLAredF 100 µm PLAredF PLAredF PLAredF PLAredF 30 µm PLAredF 100 µm PLAredF PLAredF PLAredF PLAredF 30 µm PLAredF 100 µm 32

39 AlbuminF particles Fluorescent albumin particles consist of crosslinked bovine serum albumin (BSA) or human serum albumin (HSA), resp., on request. They are prepared with a mean diameter of 250 nm and show a green fluorescence with an excitation at 485 nm and an emission at 510 nm. The fluorescent albumin particles are supplied in water AlbumingreenF fluorescent particles 33

40 34 fluorescent particles

41 Fluorescent magnetic particles page nanomag CLDF 36 BNFF particles 37 BNFStarchredF 37 BNFDextranredF 37 PLAMF particles 38 35

42 nanomag CLDF fluorescent magnetic particles Fluorescent magnetic particles allow the application of magnetic properties together with the ability of optical visualization. nanomag CLDredF particles combine separation and detection purposes. They show a red fluorescence with an excitation at 552 nm and an emission at 580 nm. The nanomag CLDredF particles are prepared by precipitation of iron oxide in the presence of dextran. The particles consist of about 8090% (w/w) iron oxide in a particle matrix of crosslinked dextran (MW: Da). They can not be separated with a conventional permanent magnet, but in a high gradient magnetic field. The nanomag CLDredF are supplied in water without any surfactants with an iron concentration of 2.4 mg/ml. The 300 nm nanomag CLDredF particles also have a red fluorescence with an excitation at 552 nm and an emission at 580 nm. They are prepared by the coreshell method and consist of an iron oxide core in a matrix of crosslinked dextran. They can easily be separated with a conventional permanent magnet. Confocal imaging of the location of LAMP1 conjugated nanomag CLDredF in INS1 cells (scale bar: ) (Zhang E et al., ACS Nano, 2014;8(4): ) The nanomag CLDredF particles are available with a surface or with amino groups on the surface for the covalent binding of proteins, antibodies or other molecules nanomag CLDredF nanomag CLDredF nanomag CLDredF nm

43 BNFF particles Labeling of mesenchymal stem cells with polydlysine modified BNFStarchredF (blue: nucleus, green: mitochondria) The BNF particles can be separated with strong conventional permanent magnets and easily be filtered through 0.2 filters. BNFredF are available with a surface or with amino groups on the surface for the covalent binding of proteins, antibodies or other molecules. Strept coated BNFredF particles are provided for the binding of biotinylated antibodies, dyes, oligonucleotides or other molecules. All BNFredF particles are supplied in PBS buffer (ph = 7.4) without any surfactants. The coated BNFredF particles are stabilized with 0.02 % sodium azide BNFStarchredF BNFStarchredF BNFStarchredF BNFDextranredF BNFDextranredF BNFDextranredF 37 fluorescent magnetic particles BNFStarchredF and BNFDextranredF particles are thermally blocked at room temperature and show specific interaction with alternating magnetic fields. They are prepared via the coreshell method with a core of 7580% (w/w) magnetite with crystallite diameters of about 20 nm and a shell of crosslinked dextran (BNFDextranredF) or crosslinked hydroxyethyl starch (BNFStarchredF). Fluorescent and magnetic BNF particles combine separation and detection purposes with a red fluorescence (excitation at 552 nm and emission at 580 nm).

44 PLAMF particles fluorescent magnetic particles Fluorescent and magnetic poly(lactic acid) particles combine the biocompatibility of the particles with separation and detection purposes. They consist of magnetite (40% w/w) in a matrix of poly(d,llactic acid) with a molecular weight of Da. The particles are available with mean diameters of 30 µm and 100 µm (broader size distributions) and can be loaded with drugs on request. We provide these magnetic particles with green or red fluorescence. The PLAMgreenF particles have an excitation at 502 nm and an emission at 527 nm. The PLAMredF particles have an excitation at 552 nm and an emission at 580 nm. Fluorescence microscopy image of 100 µm PLAMgreenF PLAMgreenF 30 µm PLAMgreenF 100 µm PLAMredF 30 µm PLAMredF 100 µm 38

45 White particles page 40 Plain particles 41 Functionalized particles 43 Protein coated particles 43 Particles with gold labeling 45 Particles with NTA or NiNTA groups on the surface 45 Particles with other chelators on the surface 46 Particles with hydrophobic surfaces 46 Particles with TiO2 or Al2O3coating Plain particles 48 Functionalized particles 49 Protein coated particles 51 Collagen and chitosan coated particles 52 Particles with positive or negative surface charges 53 Particles with NTA or NiNTA groups on the surface 54 Particles with hydrophilic surfaces 55 Particles with hydrophobic surfaces 56 PLA particles 57 IDAlatex particles 58 Albumin particles 58 39

46 are produced by hydrolysis of orthosilicates and related compounds. The amorphous silica matrix provides a hydrophilic surface with terminal SiOHbonds. The particles are monodisperse and nonporous in the size range of 10 nm to 1, with a density of 2.0 g/cm³. They possess broader size d istributions in case of porous silica particles with adjusted diameters between 3 and 20 microns and a density of 1.8 g/cm³. particles are extremely stable in organic solvents and aqueous buffers. REM image of microspheres,, 1 on a filter membrane Silica particles () are designed with the surface functionalities OH (),,, Nhydroxysuccinimide (NHS) or epoxy for the covalent binding of proteins, antibodies or other molecules, white particles are available with covalently bound proteins (,, protein A, albumin), can be provided with covalently bound antibodies on request, can be offered with the nickel(ii) chelator nitrilotriacetic acid (NTA) or ready to use with the corresponding nickel complex (NiNTA) for the binding of histidine labeled proteins, are also suitable for the complexation of metal ions with covalently bound chelators on the particle surface (EDTA), are provided with gold labeling (other metal labelings (e.g. with Pt, Pd, Ag) are available on request), can be modified with other inorganic structures (cotitania or coalumina), are available with various hydrophobic/ organic surfaces (trimethylsilyl (TMS), octadecyl (C18), acrylate). particles > 300 nm can be provided in organic solvents or as powder on request. We do not recommend to dry the smaller particles (10 nm 200 nm). In case these nanoparticles are needed in powder form we suggest a previous trimethylsilyl coating in order to generate hydrophobic surface properties. For other applications requesting an organic surface modification, acrylate coated silica particles were designed, which are available as suspension in ethanol. Silica particles 200 nm can easily be separated by simple sedimentation or centrifugation. Additionally, particles < 200 nm can be separated by ultracentrifugation or washed by SEC (size exclusion chromatography) or dialysis. 40

47 Plain particles Plain particles have a hydrophilic surface with terminal SiOHgroups without any additional functional groups on the surface. The particles are available in the size range of 10 nm to 20 µm and are supplied in water or as powder on request. The nonporous particles have small monomodal size distributions with polydispersity indices < 0.2. The larger porous particles have broader size distributions with mean diameters of 3 ± 0., 4 ± 0., 5 ± 0.8 µm, 10 ± 2., 15 ± 4 µm and 20 ± 11.. The particles are supplied in water without any surfactants nm nm nm nm nm nm nm nm nm , µm white particles TEM image of particles,, 41

48 Functionalized particles particles are available with the basic surface functionalities and in the size range from 30 nm to 20 µm. white particles For conjugation of amino groups of target molecules the groups on the particles can be activated with carbodiimide or the amino groups with glutaraldehyde. For conjugation of thiolated molecules the amino groups can be further functionalized for example with SPDP or maleimide groups nm nm nm nm nm , µm nm nm nm nm nm , µm particles with diameters of 300 nm to 20 µm are also provided with Nhydroxysuccinimide (NHS) or epoxy groups for the covalent binding of proteins, antibodies or other molecules. NR3+ modification shifts the zeta potential into positive direction. All functionalized particles are supplied in water without any surfactants. Only the NHS and epoxymodified silica particles are provided as powder to preserve their reactivity with hydroxyl, amino or thiol groups. 42

49 NR nm NR nm NR3+ NR3+ NR3+ 1, epoxy 300 nm 0,1 g epoxy 0,1 g epoxy 0,1 g epoxy 1, 0,1 g epoxy 0,1 g epoxy 0,1 g epoxy 0,1 g epoxy 1 0,1 g epoxy 20 µm 0,1 g NHS 300 nm NHS NHS NHS 1, NHS NHS NHS NHS NHS 20 µm white particles Protein coated particles particles are available with covalently bound in the size range of to 20 µm. particles with an, protein A or albumin (BSA) coating are available in the size range from 300 nm to 20 µm. Avidin and bind biotinylated molecules easily and with a high affinity, while protein A picks up and orients IgGs from a mixture of species. The albumin (BSA) coating makes the surface of the silica particles more biocompatible if needed. A coating with HSA is available on request. The protein coated particles are supplied in PBS buffer (ph=7.4) with 0.02 % sodium azide. 43

50 white particles nm , µm nm nm , µm nm nm , µm albumin (BSA) 300 nm albumin (BSA) albumin (BSA) albumin (BSA) 1, albumin (BSA) albumin (BSA) albumin (BSA) albumin (BSA) albumin (BSA) 20 µm 44

51 Particles with gold labeling particles are provided with gold labeling in the size range of to 20 µm and are supplied in water. The gold labeling allows the binding of thiolated biomolecules. Other metal labels (e.g. Pt, Pd, Ag) are available on request Au Au Au Au Au 20 µm Particles with NTA or NiNTA groups on the surface Recombinant proteins containing a 6xhistidinetag can be purified by NiNTA (nickelnitrilotriacetic acid) chromatography which is based on the interaction between a transition Ni2+ ion immobilized on a matrix and the histidine side chains. Following washing of the matrix 6xhistidinetag fusion proteins can be eluted by adding free imidazole or EDTA or by reducing the ph NTA 300 nm NTA NTA NTA 1, NTA NTA NTA NTA NTA 20 µm NiNTA 300 nm NiNTA NiNTA NiNTA 1, NiNTA NiNTA NiNTA NiNTA NiNTA 20 µm 45 white particles particles are offered with the nickel(ii) chelator nitrilotriacetic acid (NTA) or ready to use with the corresponding nickel complex (NiNTA) for the binding of histidine labeled proteins in the size range of 300 nm to 20 µm. They are supplied in water.

52 Particles with other chelators on the surface particles are also offered for the complexation of metal ions with covalently bound chelators on the particle surface. particles with EDTA surface functionalities are available in the size range of 300 nm to 20 µm for the complexation of e.g. Cu 2+, Ni2+, Fe3+ and Co3+. Thus silica particles with EDTA surface can also be used for the complexation of radioactive metal ions. These particles are supplied in water EDTA 300 nm EDTA EDTA EDTA 1, EDTA EDTA EDTA EDTA EDTA 20 µm white particles Particles with hydrophobic surfaces Some applications require a gentle hydrophobic organic coating of silica particles, especially if an organic polymer coating is necessary for the application. particles possessing an acrylate surface with terminal carboncarbon double bonds are available in the size range of 30 nm to as suspension in ethanol. particles are also available with a strong hydrophobic trimethylsilyl (TMS) surface in the size range of 50 nm to 20 µm and with an octadecyl (C18) surface in the size range of 300 nm to 20 µm. These hydrophobic particles are provided as powders, that allow a direct suspension of the particles in organic solvents and provide a high selectivity for polar, neutral and moderately non polar pharmaceuticals, natural products, food additives, organic chemicals and biologicals acrylate 30 nm acrylate 50 nm acrylate 70 nm acrylate acrylate 200 nm acrylate 300 nm acrylate acrylate 46

53 TMS 50 nm 0,25 g TMS 0,25 g TMS 200 nm TMS 300 nm TMS TMS TMS 1, TMS TMS TMS TMS TMS 20 µm C nm C C C18 1, C C C C C18 20 µm Particles with TiO2 or Al2O3coating particles are provided with other inorganic structures on the surface. Silicacotitania particles are available in the size range of 300 nm to 20 µm, and silicacoalumina particles in the size range of 300 nm to. Both particle types are supplied in water TiO2 300 nm TiO TiO TiO2 1, TiO TiO TiO TiO TiO2 20 µm Al2O3 70 nm Al2O3 300 nm Al2O Al2O3 47 white particles

54 particles are monodisperse particles from polystyrene, substituted polystyrenes, polystyrenecopolymers, polymethacrylate derivatives or crosslinked polymers. The smallest particles are provided with a diameter of 25 nm with a polymethacrylate matrix. The larger particles in the size range of 50 nm to 100 microns consist of a polystyrene matrix. particles are available as standard products with a large variety of surface modifications for specific applications. SEM image of particles,, Polystyrene / polymethacrylate particles () are designed with the surface functionalities, epoxy and for the covalent binding of proteins, antibodies or other molecules, white particles are available with covalently bound proteins (,, protein A, albumin) or other biomolecules (chitosan, collagen), can be offered with the nickel(ii) chelator nitrilotriacetic acid (NTA) or ready to use with the corresponding nickel complex (NiNTA) for the binding of histidine labeled proteins, are available with various hydrophilic surfaces (PEG 300, alkyloh) and hydrophobic surfaces (octyl (C8), octadecyl (C18) or acrylate). Plain particles Plain particles have no additional coatings or special functional groups on the surface. They are made by radicalic polymerization and contain traces of negatively charged sulfate groups on the surface. They are used as is for many applications. After protein coating they are applied in latex agglutination tests and in a large variety of immunoassays. They can serve as size scale for microscopic images of bacteria or other objects of your interest. The particles are available in the size range of 25 nm to. 48

55 nm nm nm µm µm µm particles are designed with the surface functionalities and NH 2 in the whole size range of 25 nm to 100 µm and with epoxy groups in the size range of to. The particles are stable in aqueous media and to some extend in DMSO. The particles are supplied in water without any surfactants. Thus the whole variety of conjugation methods for the covalent binding of proteins, antibodies or other target molecules can be applied, e.g. carbodiimide activation of groups for conjugation to amino groups, glutaraldehyde activation of amino groups for conjugation to amino compounds, maleimide or SPDP functionalization of the amino groups for conjugation of SHlabeled biomolecules, simple reaction of epoxyfunctionalized particles in a conjugation buffer at ph=9 for conjugation with amino groups or at ph=7 for reaction with SH groups of your target molecules epoxy epoxy epoxy epoxy 4 µm epoxy epoxy epoxy 7 µm epoxy 8 µm epoxy 49 white particles Functionalized particles

56 white particles nm nm µm µm µm µm µm µm µm µm nm nm nm µm µm µm µm µm µm µm µm 50

57 Protein coated particles particles are available with covalently bound, or protein A on the surface in the size range of to 100 µm. Avidin and bind biotinylated molecules easily and with a high affinity, while protein A picks up and orients IgGs from a mixture of species. particles with covalently bound albumin (BSA) on the surface are provided in the size range of to. The albumin (BSA) coating makes the surface of the polystyrene particles biocompatible if needed. A coating of particles with HSA is available on request. The protein coated particles are supplied in PBS buffer (ph=7.4) with 0.02 % sodium azide nm µm µm µm µm µm µm µm µm nm µm µm µm µm µm µm µm µm white particles 51

58 white particles nm µm µm µm µm µm µm µm µm albumin (BSA) albumin (BSA) albumin (BSA) albumin (BSA) 4 µm albumin (BSA) albumin (BSA) albumin (BSA) 7 µm albumin (BSA) 8 µm albumin (BSA) Collagen and chitosan coated particles particles are available with covalently bound collagen and chitosan in the size range of to. Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is mostly found in fibrous tissues such as tendon, ligament and skin, and is also abundant in cornea, cartilage, bone, blood vessels, the gut, and intervertebral disc. The collagen around our polystyrene particles increases the affinity to selected target tissues. Chitosan is a linear polysaccharide composed of randomly distributed β(14)linked Dglucosamine (deacetylated unit) and NacetylDglucosamine (acetylated unit). Therefore the chitosan coated polystyrene particles already contain natural amino groups and show special affinities to target surfaces. The particles are supplied in water without any surfactants. 52

59 collagen collagen collagen collagen 4 µm collagen collagen collagen 7 µm collagen 8 µm collagen chitosan chitosan chitosan chitosan 4 µm chitosan chitosan chitosan 7 µm chitosan 8 µm chitosan Particles with positive or negative surface charges particles are available with trialkylammonium groups (NR 3+) on the surface, that lead to a positive zeta potential. Corresponding sulfonated polystyrene particles (SO3H) are provided with negative zeta potentials. Both particle types are available in the size range of to 10 µm and are supplied in water without any surfactants NR NR NR NR NR3+ 4 µm NR NR NR3 + 7 µm NR3+ 8 µm NR3 53 white particles

60 SO3H SO3H SO3H SO3H SO3H 4 µm SO3H SO3H SO3H 7 µm SO3H 8 µm SO3H white particles Particles with NTA or NiNTA groups on the surface particles can be offered with the nickel(ii) chelator nitrilotriacetic acid (NTA) or ready to use with the corresponding nickel complex (NiNTA) for the binding of histidine labeled proteins in the size range of to. Recombinant proteins containing a 6xhistidinetag can be purified by NiNTA (nickelnitrilotriacetic acid) chromatography which is based on the interaction between a transition Ni2+ ion immobilized on the particle matrix and the histidine side chains. Following washing of the matrix 6xhistidinetag fusion proteins can be eluted by adding free imidazole or EDTA or by reducing the ph NTA NTA NTA NTA 4 µm NTA NTA NTA 7 µm NTA 8 µm NTA NiNTA NiNTA NiNTA NiNTA 4 µm NiNTA NiNTA NiNTA 7 µm NiNTA 8 µm NiNTA 54

61 Particles with DBCOfunctionalized surface particles with a DBCO(Dibenzocyclooctyne)functionalized surface are available with diameters of 10 and 20 µm and are wellsuited for the copperfree or strain promoted alkyneazide cycloaddition (SPAAC) under physiological conditions. Thus, azidomodified biomolecules can be efficiently bound and separated under mild centrifugation parameters. The particles are supplied in water without any surfactants DBCO DBCO 20 µm Particles with hydrophilic surfaces alkyloh alkyloh alkyloh alkyloh 4 µm alkyloh alkyloh alkyloh 7 µm alkyloh 8 µm alkyloh PEG PEG PEG PEG µm PEG PEG PEG µm PEG µm PEG 300 white particles particles are available with various hydrophilic surfaces (PEG 300, other PEG lengths on request, alkyloh) in the size range of to. These hydrophilic coatings reduce the unspecific binding of proteins significantly. The particles are supplied in water without any surfactants. 55

62 Particles with hydrophobic surfaces white particles particles are available with hydrophobic surfaces octyl (C8), octadecyl (C18) or acrylate (with terminal C=C double bonds) in the size range of to. These hydrophobic surfaces provide a high selectivity for polar, neutral and moderately nonpolar pharmaceuticals, natural products, food additives, organic chemicals and biologicals. The particles are supplied in water without any surfactants acrylate acrylate acrylate acrylate 4 µm acrylate acrylate acrylate 7 µm acrylate 8 µm acrylate C C C C8 4 µm C C C8 7 µm C8 8 µm C C C C C18 4 µm C C C18 7 µm C18 8 µm C18 56

63 PLA particles Poly(lactic acid) (PLA) particles consist of poly(d,llactic acid) with a molecular weight of Da. They are available with diameters of and in small size distributions and with mean diameters of, 30 µm and 100 µm in broader size distributions. white particles The PLA particles are established in the field of drug encapsulation in connection with a controlled drug release. The halflife time of the beads under in vivo conditions mainly depends on the molecular weight of the polymers and increases with the molecular weight of the polymer. The PLA particles are available without any functional groups (), with or NH 2 groups in the whole size range from to 100 µm or with collagen on the surface for 30 µm and 100 µm PLA particles. The PLA particles are supplied in water and can be loaded with drugs on request. SEM image of 100 µm PLA particles with low and high magnification (scale bar: 100 µm) (Mima Y et al., Plos ONE, 2012;7(4),e35199) PLA particles PLA particles PLA particles PLA particles 30 µm PLA particles 100 µm PLA particles PLA particles PLA particles PLA particles 30 µm PLA particles 100 µm PLA particles PLA particles PLA particles PLA particles 30 µm PLA particles 100 µm PLA particles collagen 30 µm PLA particles collagen 100 µm 57

64 IDAlatex particles, Albumin particles Iminodiacetic acid (IDA) particles were specially designed for the enrichment of metal ions from large volumes of sea water. The direct introduction of seawater to an Inductively Coupled Plasma Mass Spectrometer (ICPMS) can cause a number of serious problems. The high dissolved solids of seawater can suppress analyte signal, cause interelement interferences and clog the interface sampler and skimmer cones. An alternative is a sample preparation method that can selectively preconcentrate trace metals of interest while having much less affinity for major matrix components such as Na, Ca, and Mg. IDALatex particles can be used for preconcentration / matrix elimination of seawater. white particles These monodisperse polymer particles with a mean particle diameter of about 300 nm have a very high density of iminodiacetic acid (IDA)groups on the surface and show an excellent binding capacity for trace metals (e.g. Mn, Co, Ni, Cu, Zn, Cd, Pb, U) in neutral to basic phrange. The binding capacity for Nickel(II)ions is about 200 µmol per g of IDAlatex. The IDAlatex particles are supplied in water. For further individual surface modifications the IDAlatex particles are also provided with a high density of amino groups IDALatex 300 nm IDALatex IDA 300 nm Albumin particles consist of crosslinked bovine serum albumin (BSA). They can also be made from human serum albumin (HSA) on request. The albumin particles have a mean diameter of and are supplied in water. They serve as model particles in ecological systems, e.g. for the determination of grazing rates of microorganisms and for studies on essential food compartments in ecology. The albumin particles can be unspecifically labeled with radionuclides for applications in nuclear medicine Albumin particles 58

65 Colored particles Page color 60 black 60 blue and red 61 color 62 PLAcolor particles 63 59

66 color Coloured silica particles are produced by hydrolysis of orthosilicates and related compounds. They are available with black, red or blue colour. Coloured silica particles have a hydrophilic surface with terminal SiOHbonds, are available with a surface (SiOH) or with groups on the particle surface for the covalent binding of proteins, antibodies, oligonucleotides, enzymes or other molecules. are provided in the size range of to as monodisperse and nonporous particles with a density of 2.0 g/cm³, have broader size distributions in the area of the porous silica particles with adjusted diameters between 3 and 20 microns and a density of 1.8 g/cm³, colored particles are applied for membrane checks, flow investigations or the quality of antibody coupling procedures on surfaces. black Black silica particles (black) have a coating of black ink, that is stable in aqueous media, but not in organic solvents. They are available in the size range of to 100 µm as powder black black black black black 20 µm black 100 µm 60

67 color blue and red red particles and blue particles contain a high amount of covalently bound dye in the silica matrix. red and blue, suspension in water, particle size, Red and blue silica particles (red and blue) are available with amino groups () on the surface for the covalent binding of proteins, antibodies, oligonucleotides, enzymes or other biomolecules. The particles have broader size distributions with adjusted diameters between 3 and 20 microns. They are porous and have a density of 1.8 g/cm³. The particles are supplied in water without any surfactants. blue and red particles are extremely stable in organic solvents and buffers blue blue blue blue blue blue blue 20 µm red red red red red red red 20 µm 61 colored particles Plain red and blue silica particles (red and blue) have a hydrophilic surface with terminal SiOHbonds. They are monodisperse and nonporous in the size range of to.