U.S. patent application number 13/799021 was filed with the patent office on 2013-09-19 for system and method for superheating and/or supercooling of liquids and use of the system and/or method.
This patent application is currently assigned to Kist Europe-Korea Institute of Science and Technologie Europe Forschungsgesellschaft mbh. The applicant listed for this patent is Kist Europe-Korea Institute of Science and Technologie Europe Forschungsgesellschaft mbh. Invention is credited to Matthias ALTMEYER, Pavel NEUZIL, Adam PRIBYLKA.
Application Number | 20130240180 13/799021 |
Document ID | / |
Family ID | 49043826 |
Filed Date | 2013-09-19 |
United States Patent
Application |
20130240180 |
Kind Code |
A1 |
NEUZIL; Pavel ; et
al. |
September 19, 2013 |
SYSTEM AND METHOD FOR SUPERHEATING AND/OR SUPERCOOLING OF LIQUIDS
AND USE OF THE SYSTEM AND/OR METHOD
Abstract
System and method for for superheating and/or supercooling of
liquids and use of the system and/or method, wherein the liquid is
within a capillary tube, wherein there is at least one heating
and/or cooling means for heating the liquid above boiling point of
the liquid at ambient pressure or cooling the liquid below freezing
point of the liquid at ambient pressure, wherein the at least one
heating and/or cooling means is in thermal contact with the
capillary tube in an area, in which there is liquid inside the
capillary tube, and wherein the capillary tube is scratch-free at
its inner surface.
Inventors: |
NEUZIL; Pavel;
(Saarbruecken, DE) ; ALTMEYER; Matthias;
(Saarbruecken, DE) ; PRIBYLKA; Adam;
(Saarbruecken, DE) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Technologie Europe Forschungsgesellschaft mbh; Kist Europe-Korea
Institute of Science and |
|
|
US |
|
|
Assignee: |
Kist Europe-Korea Institute of
Science and Technologie Europe Forschungsgesellschaft mbh
Saarbruecken
DE
|
Family ID: |
49043826 |
Appl. No.: |
13/799021 |
Filed: |
March 13, 2013 |
Current U.S.
Class: |
165/104.26 |
Current CPC
Class: |
F28D 15/04 20130101;
F28F 13/18 20130101; F28D 7/00 20130101 |
Class at
Publication: |
165/104.26 |
International
Class: |
F28D 15/04 20060101
F28D015/04 |
Foreign Application Data
Date |
Code |
Application Number |
Mar 14, 2012 |
DE |
10 2012 102 163.5 |
Claims
1. Open system for superheating and/or supercooling of liquids,
wherein the liquid is within a capillary tube, wherein there is at
least one heating and/or cooling means for heating the liquid above
boiling point of the liquid at ambient pressure or cooling the
liquid below freezing point of the liquid at ambient pressure,
wherein the at least one heating and/or cooling means is in thermal
contact with the capillary tube in an area, in which there is
liquid inside the capillary tube, and wherein the capillary tube is
at least nearly free of nucleation centers at its inner
surface.
2. Open system according to claim 1, wherein the area of the with
liquid filled capillary tube extends on both sides beyond the area
of the capillary tube where the heating and/or cooling means are in
thermal contact with the capillary tube.
3. Method for superheating and/or supercooling of a liquid under
use of an open system according to claim 1, wherein the open system
is operated in a flow-through mode.
4. Method according to claim 3, wherein the flow-through mode is
accomplished by the operation of at least one feeder screw or pump
for conveying the liquid through the area of the capillary tube
where the at least one heating and/or cooling means are in thermal
contact with the capillary tube.
5. Method for superheating and/or supercooling of a liquid under
use of an open system according to claim 1, wherein the open system
is operated in a batch mode.
6. Use of an open system and/or a method according to claim 1,
wherein the liquid is water or an organic solvent.
7. Use according to claim 1, wherein the liquid contains
biomolecules, wherein said biomolecules are dissociated when
superheated or supercooled and exposed for an exposure period.
8. Use according to claim 7, wherein the biomolecules are
biopolymers selected from the group consisting of proteins, nucleic
acids, carbohydrates and lipids.
9. Use according to claim 7, wherein the biomolecules are proteins
or peptides.
10. Use according to claim 7, wherein the biomolecules are selected
from the group consisting of secondary metabolites, sugars,
polycyclic aromatic carbohydrates, phospholipids, glycolipids,
sterols, glycerolipids, vitamins, hormones, neurotransmitters,
fatty acids, isoprenoids, lantibiotics and polyketides.
11. Use according to claim 1, wherein the liquid contains
prokaryotes, eukaryotes or viruses.
Description
[0001] The present invention relates to a system and method for
superheating and/or supercooling of liquids and use of the system
and/or method.
[0002] Superheating means: Bringing the temperature of a liquid
above the boiling temperature at a defined pressure (here: the
ambient pressure) without vaporisation of the liquid. Supercooling
means: Bringing the temperature of a liquid below the freezing
temperature at a defined pressure by keeping the liquid in the
liquid phase without change of the phase.
[0003] Fast, reliable and inexpensive methods for e.g. protein
identification and analysis of posttranslational modifications are
important as proteins are being used as tools, targets and
therapeutics.
[0004] For e.g. protein identification mass spectrometry (MS) of
proteins is the state-of-art technique. However, for mass
spectrometry (MS)-based identification of proteins a pre-treatment
step to break the proteins into peptides is required for peptide
mass fingerprinting (PMF) or peptide fragment fingerprinting.
[0005] Typically an enzymatic reaction based on proteases such as
trypsin is employed. Besides the enzymatic reaction, researchers
also use chemical degradation methods. Both processes are time
consuming and expensive.
[0006] A more general approach than enzyme-based target molecule
hydrolysation can be performed by energy-based destruction of
peptide bonds within the proteins.
[0007] As known from MS fragmentation reactions, increasing amounts
of energy lead to more unspecific fragmentation patterns and
finally to complete atomization of the original molecule.
[0008] The rate of protein fragmentation is highly energy-dependent
thus increasing temperature will dramatically increase the reaction
rate. However, maximum achievable temperature is typically limited
by the solvent boiling point. In case water is used as solvent, the
solvent boiling point is 100.degree. C. at ambient pressure, if
nucleation centres inside the reaction vessel are abundant.
[0009] Nevertheless, if no nucleation centres are present, water
temperature can be increased above the boiling point of water at
ambient pressure. This water, which is not boiling but has a
temperature above its boiling point, is called superheated
water.
[0010] It would therefore be of great benefit if there were a
system, which is able to superheat or supercool liquids so that
energy-based dissociation of molecules in liquids can be
achieved.
[0011] It is the object of the invention to provide a system which
allows superheating and or supercooling of liquids in capillary
tubes.
[0012] With reference to claim 1 the object is met by an open
system for superheating and/or supercooling of liquids, wherein the
liquid is within a capillary tube, wherein there is at least one
heating and/or cooling means for heating the liquid above boiling
point of the liquid at ambient pressure or cooling the liquid below
freezing point of the liquid at ambient pressure, wherein the at
least one heating and/or cooling means is in thermal contact with
the capillary tube in an area, in which there is liquid inside the
capillary tube, and wherein the capillary tube is at least nearly
free of nucleation centers at its inner surface.
[0013] The meaning of "at least nearly free of nucleation centers"
means that the inner surface is at least nearly free of scratches,
impurities or other imperfections on the inner surface.
[0014] Open system means that the surface of the liquid, which is
not in contact with the surface of the capillary tube, is in
contact with ambient pressure.
[0015] Although the main point of application of the superheating
and/or supercooling is described with reference to the treatment of
proteins, peptides and biomolecules it has to be understood that
the invention for superheating and/or supercooling of liquids can
also be used in other applications.
[0016] Capillary tube means preferentially a cylindrical body
wherein the liquid is inside this body. However, also capillary
tubes with other inner geometric shape are imaginable. It is of
importance that the inner surface of the capillary tube is free of
nucleation centers (e.g. scratches or impurities).
[0017] The heating or cooling means are in thermal contact with the
outer surface of the capillary tube. Thereby the inner volume of
the capillary tube can be heated or cooled. Therefore it is
advantageous if the material of the capillary tube has a high
thermal conductivity.
[0018] The capillary tube can be made of glass, thermostable
plastics or metal. The inner surface of this tube shall be at least
nearly free of nucleation centers. This means that the inner
surface should be scratch-free and also free of impurities. The
glass can be treated as it is known for example in the field of
advanced optic systems to get the surface at least nearly free of
nucleation centers. It is also envisioned that the glass capillary
can be coated (chemically modified) on its inner surface with e.g.
silanes, silane-based surface modifications, surfactants or
polymers such as e.g. polyelectrolytes. The inner surface of the
metal capillary tube can be high polished or perhaps be coated, as
described above for glass. The capillary tube can be made of
thermostable plastics such as, but not limited to, PFA, PSA, PTFE,
PE, PP. It can also be possible to bring another liquid into the
tube, whereby this other liquid is phobic with respect to the
liquid to be heated. This means that the two liquids keep separated
and have a sharp boarder between the two liquids. The other liquid
builds a thin film over the inner surface of the capillary tube.
This leads to a "polished" inner surface, which it at least nearly
free of nucleation centers because of the surface tension of the
other liquid.
[0019] It is belonging to the invention that inner diameter of the
capillary tube is in the range between 1 .mu.m to 250 .mu.m.
However, so far capillary tubes with an inner diameter of 5, 50,
100 and 150 .mu.m have been tested positively for use of the
invented system.
[0020] With respect to claim 2 it is within the scope of the
invented system that the area of the with liquid filled capillary
tube extends on both sides beyond the area of the capillary tube
where the heating and/or cooling means are in thermal contact with
the capillary tube.
[0021] This is advantageous, because there is a temperature
gradient in the liquid beyond the area in which the heating or
cooling means are placed. Therefore there is no change of phase
inside the liquid as it might happen if the outer surface of the
liquid would be in the area of the capillary tube, which is
directly heated.
[0022] Hence, according to claim 3, it is further advantageous that
the open system is operated in a flow-through mode.
[0023] It is beneficial to operate the system in flow-through mode
for samples (liquids), for which only a short exposure period /
time is required. It is also of importance that, by operating the
system in flow-through mode, no manual sample handling is required.
By avoidance of manual sample handling, the contamination risk of
the sample can be reduced. However, it is within the scope of the
invention, that the system can be connected to other flow-through
processing systems, such as for example high-performance liquid
chromatography (HPLC).
[0024] As described in claim 4 the flow-through mode can
advantageously be accomplished by the operation of at least one
feeder screw or pump for conveying the liquid through the area of
the capillary tube where the at least one heating and/or cooling
means are in thermal contact with the capillary tube.
[0025] It is within the scope of the invention that the feeder
screw or pump can be operated with a defined speed, therefore
conveying an accurate volume of liquid with a precise flow rate
through the area of the capillary tube where the at least one
heating and/or cooling means are in thermal contact with the
capillary tube. The pump can be a syringe pump or a capillary pump
or any other pump which allows conveyance of liquids.
[0026] It is hereby also envisaged that the operation of the feeder
screw or pump can be controlled by a computer or such, which allows
programming the feeder screw or pump with a defined sequence of
slow and fast flow rates. The control can be of the kind of an
open-loop control or a closed-loop control. It is possible to have
the liquid for a defined time in the area, where the liquid is
heated. Thereby it is possible to bring a defined amount of heat
into the liquid.
[0027] As described in claim 5, it is also within the scope of the
invention that the open system is operated in a batch mode.
[0028] This is favorable in case extraordinary stable molecules
require long exposure times for dissociation. For these, it might
not be possible to realize the long exposure times in a
flow-through mode, even at very low flow rates.
[0029] Claim 6 refers to a preferred use of one of the above
mentioned systems or methods. It is therefore a preferred
embodiment of the invention that the liquid is water or an organic
solvent.
[0030] Many substances dissolve in water and it is commonly
referred to as the universal solvent.
[0031] As described in claim 7, it is feasible within the scope of
the invention that the liquid contains biomolecules, wherein said
biomolecules are dissociated when superheated or supercooled and
exposed for an exposure period.
[0032] Dissociation means: Any kind of destruction of biomolecules,
including energy-based hydrolysis, fragmentation, degradation but
also treatment with chemicals, enzymes or metals for
fragmentation.
[0033] Therefore the invention is of a very important relevance for
the treatment of biomolecules for scientific applications.
[0034] The exposure period for dissociation of biomolecules is
strongly influenced by the character of the molecule (e.g. amino
acid sequence for proteins and peptides). However, it is favorable
for the use of the invention that the exposure period is in the
range of seconds to a few minutes.
[0035] As described in claim 8, it is envisaged that the
biomolecules are biopolymers selected from the group consisting of
proteins, nucleic acids, carbohydrates and lipids.
[0036] As described in claim 9, it is a preferred embodiment of the
invention that the biomolecules are proteins or peptides.
[0037] Superheating-induced dissociation of proteins and peptides
can be monitored by mass spectrometry. Optimizing of superheating
conditions such as temperature and exposure time could lead to
partial hydrolysis of sample molecules.
[0038] Simple samples such as di- and tri-peptides were used to
demonstrate feasibility of the method. Subsequently, a set of short
oligo-peptides can be fragmented under superheated conditions.
Employing small molecules such as di- and tri-peptides can build a
basis to calculate the masses of all possible reaction products.
These products could result from original peptide fragmentation,
adduct formation or elimination.
[0039] Partial hydrolysis could build a basis to identify
sequence-specific weak points in peptide backbones.
[0040] In an ideal case, the invention can be used to increase the
knowledge and experience in the mechanism of superheat-induced
molecule decay.
[0041] Furthermore it is possible to predict hydrolysation
products.
[0042] Finally, it may be possible to identify superheat-destroyed
proteins in a PMF-like measurement by the peptide formation
patterns.
[0043] Superheat-induced hydrolysation products could easily be
detected by product mass and fragmentation behaviour in tandem mass
spectrometry analysis. Therefore, the available MS systems such as
electrospray ionization (ESI), quadrupole-ion trap/matrix assisted
laser desorption ionization-tandem time of flight (MALDI-TOF.sup.2)
can help in mass analysis and structure elucidation (de novo
sequencing) of superheat-resulting fragments.
[0044] The superheating technique could replace tryptic digestion
of proteins. It would dramatically shorten reaction time currently
required be enzymatic methods from typical few hours to seconds.
Subsequently, the peptide analysis by mass spectrometry would then
give the same level of information (PMF) in the "microfluidics
meets proteomics"-approach as compared to much slower and far more
expensive proteolytic digests.
[0045] Beside the identification of proteins other important
factors must be analysed to determine e.g. activity, subcellular
location and destiny of the molecule. Many different
posttranslational protein-modifications (PTMs) are known to have
influence on these parameters. Some of these groups are difficult
to analyse, because of impossibility of specific manipulation. In
case of glycosylations, mass difference before and after enzymatic
cleave-off of glycans can be used to calculate chemical formula of
the sugar molecules. In comparison to high energy transfer to such
molecules is other systems (e.g. in from MSMS reaction), also
superheating should provide random fragmentation patterns in amino
acid side chains, protein- and peptide- modifications. Today, many
hydrolysing or manipulating enzymes for PTMs are unknown.
Superheating could close this gap to identify different steps of
degradation processes in protein-modifying groups, finally for
detailed analysis of such structures. Superheat may provide a
method to treat the multitude of PTMs.
[0046] Superheating can replace a number of hydrolysation enzymes
currently used in daily laboratory processes, including the
digestion of DNA, fatty acids, isoprenoids and polyketides. In
particular, lantibiotics are of special interest due to
non-existence of hydrolysing enzymes to a majority of them.
[0047] Hence, it is within the scope of the invention that the
biomolecules are selected from the group consisting of secondary
metabolites, sugars, polycyclic aromatic carbohydrates,
phospholipids, glycolipids, sterols, glycerolipids, vitamins,
hormones, neurotransmitters, fatty acids, isoprenoids, lantibiotics
and polyketides.
[0048] With respect to claim 11, it is also within the scope of the
invention that the liquid contains prokaryotes, eukaryotes or
viruses.
[0049] Hereby it is envisioned that the system can be used for e.g.
fast DNA or RNA extraction without addition of extraction
solutions. The invented system allows a fast, simple, and
inexpensive method for preparing e.g. genomic DNA for PCR
amplification, genotyping, genetic studies, human identity testing,
viral/microbial screening or other uses.
[0050] Nevertheless, it is also envisaged that the system can be
used to serve as a unique tool for fragmentation of water insoluble
molecules.
* * * * *