Classifications

• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
  • B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
  • B01J20/28002—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their physical properties
  • B01J20/28004—Sorbent size or size distribution, e.g. particle size
  • B01J20/28007—Sorbent size or size distribution, e.g. particle size with size in the range 1-100 nanometers, e.g. nanosized particles, nanofibers, nanotubes, nanowires or the like
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
  • B01J20/02—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising inorganic material
  • B01J20/06—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising inorganic material comprising oxides or hydroxides of metals not provided for in group B01J20/04
  • B01J20/08—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising inorganic material comprising oxides or hydroxides of metals not provided for in group B01J20/04 comprising aluminium oxide or hydroxide; comprising bauxite
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
  • B01J20/281—Sorbents specially adapted for preparative, analytical or investigative chromatography
  • B01J20/282—Porous sorbents
  • B01J20/284—Porous sorbents based on alumina
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
  • B01J20/281—Sorbents specially adapted for preparative, analytical or investigative chromatography
  • B01J20/286—Phases chemically bonded to a substrate, e.g. to silica or to polymers
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J2220/00—Aspects relating to sorbent materials
  • B01J2220/50—Aspects relating to the use of sorbent or filter aid materials
  • B01J2220/54—Sorbents specially adapted for analytical or investigative chromatography
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
  • G01N30/02—Column chromatography
  • G01N30/50—Conditioning of the sorbent material or stationary liquid
  • G01N30/52—Physical parameters
  • G01N2030/524—Physical parameters structural properties

Definitions

• the invention is related to materials solution used in separation of fluid components with the purpose of their simultaneous or consequent analysis.
• the separation methods based on pure filtration, Knudsen diffusion, adsorption, dialysis or osmosis are explicitly excluded.
• the analytical methods might be spectrometry, spectroscopy, etc. in any combination.
• One of particular example of the analysis methods is bio-analysis (analysis and separation of biological samples such as blood plasma, saliva or urine) with ultra-high pressure liquid chromatography (UHPLC).
• Fast or ultra-fast separation methods are good tools to satisfy the necessity of reducing the total analysis time in bio-analysis where an increasing number and variety of samples is expected, and in areas where results must be obtained fast. Additionally, the number of target and non-target compounds is also increasing in some of these areas, especially when addressing drug development, abuse and threat substances, and doping control issues.
• Japanese patent JP2004315331 discloses a filler for high-performance chromatography column as composite particles having the form wherein porous silica particles with the particle size of 500-20000 nm having ten or less micro pores with the holes diameter of 5-20 nm are bonded in a gourd shape.
• the goal of that invention is to provide a filler having a smaller pressure loss than a totally porous particle filler showing the theoretical plate height of the same degree, namely, a filler having improved separation impedance.
• the particle size is required to be reduced, and, as the particle size is reduced resistance against the flow of a moving phase is increased and the pressure loss is increased.
• US patent 8,021,967 discloses special patterned nanostructure to improve liquid transport method, based on wicking effect by arrangement of a nanoscale fibers allowing fluid to flow without any external power source.
• wick fluid transport is only possible if the fluid is wetting the solid surface to such extent that capillary pressure-driven transport greatly overrides other limiting factors such as Hagen-Poiseuille flow, inertia forces and viscous drag.
• test elements in particular diagnostic test elements, for determining the presence or concentration of biological, medical or biologically or medically effective substances including nucleic acids, proteins, viruses, microorganisms and cells, characterized in that these test elements contain nanofibers.
• the materials solution addresses problems in fast fluid components separation, and analysis is suggested to be composed of extreme ultra-high aspect ratio nanofibers having average diameters below 100 nm, preferably below 50 nm, with the ratio of length to diameter at least 100000:1. Furthermore, these nanofibers are also produced as a regular structure of co-aligned fibers, where nanoporous channels are self-established due to favorable weak bonds formation between the adjacent nanofibers. This results in open porosity fraction over 50%, preferably over 80%.
• Fig. 1 is a scanning electron microscopy (SEM) photo of the fibers.
• Fig. 2 shows results of RP-HPLC analysis of the analytes passed through the nanofibers column.
• N is the number of theoretical plates for the column of the length L .
• Any chromatographic column has its critical pressure, which is an intrinsic value meaning no chromatography separation can be achieved in finite time if the input pressure is lower than critical [4].
• permittivity k is also a function of d and the porosity, will be increasing with lower particle size. Thus most of the columns have particles diameter of 1.5-2.5 ⁇ m as otherwise the pressure drop would be too high to achieve reasonable fluid rates [1].
• the nanostructures of the present invention which as "naturally formed" with ultra-high aspect ratio and high porosity level, are capable of a substantial improvement in the UHPLC performance.
• N 10000 and for ⁇ 700 bar pressure drop the minimal achievable HETP size would be about 37 ⁇ m for 2 ⁇ m particles in the state of the art technology according to equations (1) and (2).
• HETP HETP ⁇ 10-100 nm i.e. approaching molecular-level resolution limit. In practical terms, this means a drastic decrease in separation time from 3-4 hours in the known systems down to seconds, allowing also substantial miniaturization of the UHPLC column down to millimeter-scales.
• nanofiber materials in the substrate of the present invention must withstand dry heat sterilization cycles at temperatures above 350°C, where almost all known potentially harmful substances and those of interest (peptides, DNA, hormones, drugs) and living forms (bacteria, virions) can be destroyed in a convenient time scale.
• these nanofibers can be additionally functionalized with a proper compound, or substance, or any other chemical, physical or topological methods (alike restricted access materials, synthetic antibodies, etc.), with necessary adjustment of the substrate hydro- or lyophilicity, which might not be constant along the thickness of the substrate (or the length of the column).
• a proper compound, or substance, or any other chemical, physical or topological methods like restricted access materials, synthetic antibodies, etc.
• the substrate hydro- or lyophilicity which might not be constant along the thickness of the substrate (or the length of the column).
• gradient modification of the substrate material making it essentially a functionally gradated material (FGM) may allow construction of 3D substrate [5] with additional features depending on the desired application and the analysis goals.
• the present invention discloses the substrate structure and the method of its application, which is capable of separation and/or analysis of the fluids, preferably of biological origin.
• the substrate is thus composed of the self-aligned, ultra-high aspect ratio (length: diameter > 100000:1) nanofibers ( ⁇ 50 nm diameter) with open porosity over 50%.
• the fibers are capable of withstanding high-temperature treatment over 350°C being made of inorganic materials such as oxides, which might be additionally functionalized to adjust their hydrophilicity or selectivity.
• the oxides may be selected from simple oxides, mixed oxides and oxide compounds. Simple oxides may be aluminum oxide, silicon oxide, titanium oxide or rare earth metal oxides, but other oxides may also be used.
• Mixed oxides may be Al 2 O 3 ⁇ SiO 2 , but other mixed oxide may as well be used.
• Oxide compounds may be spinels or more complex oxides.
• the nanofibers may be hydrophobic or hydrophilic.
• they may be functionalized with a third compound or molecule.
• Such compound or molecule may be an inorganic molecule, for example another oxide or material different from the substrate fiber material.
• Such molecule may also be selected from elements stable at the analysis conditions such as noble metals like Au, Pt, Ag, or C, or Si.
• Such molecule may also be an organic molecule selected from hydrocarbons, organic acids, aromatic compounds, and/or heterocyclic compounds.
• the organic compounds may contain one or more functional groups independently selected from amide, nitrate, carboxyl, hydroxyl and/or including halogen or chalcogen.
• the substrate described above could be also used as a scaffold for cultivation of living cells, bacteria, or any similar simple or combined in vitro studies.
• the method of separation and/or analysis using abovementioned substrate includes contact and transport of the fluid in question through the substrate, where the fluid is preferably of biological origin, and where the functionalized substrate might be arranged to allow a functionally gradated 3D structure, which local reaction with analyte could be measured by any suitable technique on the spot (statically) or by scanning (dynamically) across the named substrate.
• the method comprises application of an analytical probe across thickness of the substrate and registering the probe signal, which is correlated with presence or concentration of a specific compound.
• the probe may be any known analytical method probe and the application of the probe maybe static (spot) or dynamic (scanning along the substrate thickness) mode. Examples of such probe might be spectroscopy (ultraviolet, visible or infrared range; Raman, etc.) or fluorescence, which application does not require explicit output of the analyte to come out of the column in time but rather by exploring the geometrical snapshot.
• This substrate structure and the method of application allow substantial decrease of the separation and analysis time, miniaturization of the separation and analytical systems and improvement of the performance.
• the method used could be combined with other known analytical techniques.
• the ultra-high aspect ratio nanofibers based on alumina compound, of average diameter of 40 nm (Fig. 1) were cut to the appropriate size (two pieces) to fit theticiancolumn”, which was a glass test tube.
• the weight of material was about 1.34 g.
• the material was tested to withstand at least 800°C, evidencing the benefit of the invention to enable multi-use columns for separation and analysis of biological fluids.
• the analytes were chosen to have different polarity for comparison (phenol, pyridine and dimethylaniline). Standard solution of analytes was prepared in methanol with concentration 40 mM, which was diluted 10 times in toluene (final 4 mM concentration).
• Fractions (0.5-1 ml) were collected in glass vials according to eluent compositions. The gradient was used from 0...20 % iso-propanol in hexane by 2% wt. steps. Collected fractions were analyzed at first on a TLC plate by spotting every fraction on plate and exposing it under UV-lamp (254 nm). Fractions that gave a visible spot were analyzed further with RP-HPLC (Agilent Technologies).

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• Chemical & Material Sciences (AREA)
• Analytical Chemistry (AREA)
• Organic Chemistry (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Engineering & Computer Science (AREA)
• Crystallography & Structural Chemistry (AREA)
• Materials Engineering (AREA)
• Nanotechnology (AREA)
• Inorganic Chemistry (AREA)
• Solid-Sorbent Or Filter-Aiding Compositions (AREA)

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• 2015
  • 2015-08-01 EP EP15763086.4A patent/EP3174632A1/de not_active Ceased
  • 2015-08-01 WO PCT/IB2015/055845 patent/WO2016016872A1/en active Application Filing

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