Cell culture harvesting device

The invention concerns a cell culture harvesting device consisting of a scraper head with a blade and a guide strip, the scraper head and the guide strip being connected with one another only by magnetic attraction. The magnetic attraction is achieved by the fact that one of the ends of the scraper head and the guide strip which are turned toward one another have a magnet and the other has either a magnet or a material which can be magnetized by the magnet of the respective counterpart. In this way, the scraper head and the guide strip can be moved synchronously and in parallel at a distance from one another. This has the advantage that the scraper head can be placed into the cell culture vessel before a cell culture is started and can be sterilized together with it thereby eliminating the risk of contamination due to a cell culture harvesting device later being placed into the cell culture vessel. Furthermore, the scraper head can have a net-like collection container arranged on it which collects the cells lifted off the growth surface of the cell culture vessel in a manner that avoids damage to the cells.

BACKGROUND OF THE INVENTION 
1. The Field of the Invention 
The invention concerns a cell culture harvesting device with a scraper head 
having a blade with a cutting edge and a guide strip to move the scraper 
head. 
2. Related Applications 
Foreign priority benefits under Section 119 of Title 35 of the United 
States Code of German Utility Model Application No. 196 44 761.5, filed 
Oct. 29, 1996, incorporated herein by reference, are claimed for this 
application. 
3. The Relevant Technology 
Cell culture harvesting devices in the form of scrapers which have a 
scraper head and a rod-shaped stem, which is sometimes also withdrawable, 
are well-known and common laboratory equipment. Typically, the dimensions 
of the scraper head are adapted to the neck openings of common cell 
culture flasks, since it must be introduced into the cell culture vessel 
through this opening. Cultured cells grow and adhere to the curved wall of 
roller bottle-type cell culture vessels and to the flat-surfaced wall 
forming the floor in cell culture vessels having relatively flat parallel 
walls. For purposes of this disclosure, the term "floor" is used to refer 
to the growth surface of a cell culture vessel, i.e., the curved wall of 
roller bottle-type cell culture vessels or the flat-surfaced floor wall of 
other types of cell culture vessels, where cells grow and adhere and from 
which such cells need to be harvested, i.e., removed, by the cell culture 
harvesting devices in accord with the present invention as disclosed 
herein. Accordingly, conventional cell culture harvesting devices operate 
to lift the adherent cells on the floor of the cell culture vessel off the 
surface of the floor by the scraper head which is moved by the guide 
strip. 
For example, cell culture scrapers of this kind are described in the 
1995-1996 laboratory catalog of the company Nunc GmbH under the numbers 
179693 and 179707, and in the catalog of the company Baxter Diagnostics, 
Inc., Scientific Products Division under the numbers T4206-1, T4130-56, 
57, 58, T4136-36, 37, and T4160-157. In some cases, the scraper head can 
be rotated with respect to the guide strip, so that a greater area of cell 
culture growth surface can be reached. 
Cell removal devices for removing multiple cell cultures are also known 
from U.S. Pat. No. 4,004,981. The devices are utilized with cylindrical 
cell culture vessels having a number of circular cell culture growth 
surfaces stacked at a distance on top of one another parallel to the 
cylindrical front surfaces. The cell culture scraper has at least one 
scraper head which is circular in cross section and which is placed onto 
the circular cell culture growth surfaces. Rotating motions of the cell 
culture scraper and/or the cell culture growth surfaces effects lifting of 
the cells off the growth surface or pushing of the cells to the edge of 
the growth surface. If the cell culture scraper has several scraper heads, 
then several cell culture growth surfaces can be processed/harvested 
simultaneously. 
A problem encountered during cell culturing is the risk of contamination of 
the cells and/or the cell culture vessel during the process. To reduce the 
risk of contamination by introduction of cell culture scrapers of the 
previously described type into the cell culture vessel, it is necessary to 
use sterile scrapers. Therefore, some of these scrapers are offered 
already sterilized in individual packages, while others must be sterilized 
before use in a separate sterilization process. Introducing the scraper 
into the cell culture vessel and placing it onto the cell culture growth 
surface requires careful and precise handling on the part of the operating 
personnel, since otherwise the cells can easily be mechanically damaged or 
even destroyed due to insufficient care and attention. Especially with 
roller bottle-type cell culture vessels, cell culture harvesting with 
known cell culture scrapers is relatively ineffective because reaching all 
areas of the growth surface is technically very difficult and/or depends 
too much on the skill, care, and attention of operating personnel. Another 
problem with conventional cell scraper devices is seen in the fact that, 
depending on the scraper head's angle of attack, the cells which are 
lifted can accumulate in front of or behind the scraper head in such a way 
that the cells are distorted and/or damaged in the process. 
Moreover, cell culture harvesting procedures are known which lift the 
adherent cells from the growth surface of the cell culture vessel by 
adding chemical loosening fluids. Typically, knocking or vibrating the 
growth surface is used to promote this process. U.S. Pat. No. 4,556,639 
describes such a cell culture harvesting procedure and a device suitable 
for implementation thereof. According to this procedure, the cell culture 
is first placed in a flat cell culture vessel and is subjected to the 
action of an enzyme-containing solution which reduces the adhesion of the 
cells to the growth surface of the cell culture vessel. Next, the cell 
culture vessel is placed into the receptacle of an apparatus which effects 
movement of the prepared cell culture growth surface in the perpendicular 
and/or parallel direction to the growing surface. The movement can be 
produced by ultrasound. The receptacle with the cell culture vessel is 
also moved parallel to the plane of the growth surface in a direction 
which is opposite to the movement already described. Due to the actions of 
the enzyme solution and the multiple-direction movements of the cell 
culture vessel, the cells are dislodged such that these can be suitably 
removed and spatially concentrated by withdrawing the enzyme-containing 
solution containing the cells from the cell culture vessel. Manipulation 
according to the procedure described is labor-intensive and requires the 
special apparatus. In addition, the procedure is not very flexible due to 
the combination of chemical and physical methods. 
Therefore, it is the task of the invention to eliminate the disadvantages 
encountered with conventional cell culture harvesting apparatus and 
methods. In particular, it would be an advancement to provide cell culture 
harvesting devices that are simple, cost-effective, and versatile and 
which minimize the risk of contamination and the potential for distorting 
and/or damaging cultured cells during the harvesting process. 
SUMMARY AND OBJECTS OF THE INVENTION 
It is an object of the present invention to provide cell culture harvesting 
devices that are simple, cost-effective, and versatile and that can be 
used effectively with all types of cell culture vessels. 
It is a further object of the present invention to provide cell culture 
harvesting devices which minimize the risk of contamination to the cells 
and/or the cell culture vessel during the harvesting process. 
Yet another object of the present invention to provide cell culture 
harvesting devices which minimize the potential for distorting and/or 
damaging cultured cells during the harvesting process. 
These and other objects and features of the present invention will become 
more fully apparent from the following description and appended claims, or 
may be learned by the practice of the invention as set forth hereinafter. 
The present invention solves these problems by providing cell culture 
harvesting devices which use magnetic attraction to guide a scraper head, 
positioned within a cell culture vessel, with a guide strip positioned 
outside of the cell culture vessel. In particular, one of the components, 
either the scraper head or the guide strip has a magnet turned toward the 
respective other component, and the respective other component has either 
a second correspondingly turned magnet or a magnetizable material turned 
toward the first magnet such that magnetic attraction permits the scraper 
head to be guided by the guide strip. In this manner, the scraper head is 
positioned inside the cell culture vessel and the guide strip is 
positioned outside of the cell culture vessel and the necessary connection 
is effected only by the magnetic attraction. Accordingly, the cell culture 
harvesting devices in accord with the present invention are essentially 
two-part tools, the scraper head being moved by the guide strip without 
these two parts being mechanically connected with one another. If desired, 
the guide strip can be placed against the outside surface of the cell 
culture vessel floor opposite the scraper head arranged on the inside 
surface of the floor where the guide strip will be held by magnetic 
attraction. Alternatively, if desired, the position of the scraper head 
can also be secured during the cell cultivation process by a mechanical 
holder placed inside the cell culture vessel, which is made in such a way 
that the holder easily releases the scraper head when desired. In 
addition, if desired, a single guide strip can be used to secure and/or 
effect movement of several scraper heads in desired positions within a 
cell culture vessel.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
The invention concerns a cell culture harvesting device with a scraper head 
having a blade with a cutting edge and a guide strip to move the scraper 
head. As described above, cell culture harvesting devices in the form of 
scrapers which have a scraper head and a rod-shaped stem, which is 
sometimes also withdrawable, are well-known and common laboratory 
equipment. Cultured cells grow and adhere to the curved wall of roller 
bottle-type cell culture vessels and to the flat-surfaced wall forming the 
floor in cell culture vessels having relatively flat parallel walls. For 
purposes of this disclosure, the term "floor" is used to refer to the 
growth surface of a cell culture vessel, i.e., the curved wall of roller 
bottle-type cell culture vessels or the flat-surfaced floor wall of other 
types of cell culture vessels, where cells grow and adhere and from which 
such cells need to be harvested, i.e., removed, by the cell culture 
harvesting devices in accord with the present invention as disclosed 
herein. Accordingly, conventional cell culture harvesting devices having a 
scraper head and a guide strip, such as a rod or stem fixed to the scraper 
head, are introduced into cell culture vessels where the scraper head is 
then manipulated by movement of the guide strip to lift the adherent cells 
on the floor of the cell culture vessel off the surface of the floor. 
Problems with conventional cell culture harvesting devices include 
contamination from introduction of the devices into the cell culture 
vessel, difficulty in maneuvering the devices among the cells to 
effectively lift and collect the cells, and the occurrence of distortion 
and/or damage to the cells during the harvesting process. 
The present invention solves these problems by providing cell culture 
harvesting devices which use magnetic attraction to guide a scraper head, 
positioned within a cell culture vessel, with a guide strip positioned 
outside of the cell culture vessel. In particular, one of the components, 
either the scraper head or the guide strip has a magnet turned toward the 
respective other component, and the respective other component has either 
a second correspondingly turned magnet or a magnetizable material turned 
toward the first magnet such that magnetic attraction permits the scraper 
head to be guided by the guide strip. In this manner, the scraper head is 
positioned inside the cell culture vessel and the guide strip is 
positioned outside of the cell culture vessel and the necessary connection 
is effected only by the magnetic attraction. 
The cell culture harvesting devices in accord with the present invention 
are essentially two-part tools, the scraper head being moved by the guide 
strip without these two parts being mechanically connected with one 
another. Rather, it is only magnetic attraction which acts between them, 
so that the scraper head and the guide strip can be moved synchronously 
and in parallel at a distance from one another. This feature has the 
advantage that the scraper head can be placed into the cell culture vessel 
in a desirable location before a cell culture is started. In this manner, 
the scraper head can be sterilized together with the cell culture vessel 
and the risk of contamination from a cell culture harvesting device being 
subsequently introduced into the cell culture vessel is eliminated. The 
risk of contamination from the guide strip is also eliminated since the 
guide strip remains at all times outside of the cell culture vessel. If 
desired, the guide strip can be placed against the outside surface of the 
cell culture vessel floor opposite the scraper head arranged on the inside 
surface of the floor where the guide strip will be held by magnetic 
attraction. This positioning configuration is expedient, since in this way 
the scraper head and the guide strip are already fixed in the desired 
position for beginning cell culture harvesting before the cell cultivation 
process begins. In this positioning configuration, the scraper head cannot 
change its position within the cell culture vessel in an uncontrolled 
manner and possibly damage the cell culture in the process. This 
possibility is especially significant for cell culture roller bottles, 
since in this case the entire cell culture vessel is kept in permanent 
motion. Alternatively, if desired, the position of the scraper head can 
also be secured during the cell cultivation process by a mechanical holder 
placed inside the cell culture vessel, which is made in such a way that 
the holder easily releases the scraper head when desired. In addition, if 
desired, a single guide strip can be used to secure several scraper heads 
in desired positions within a cell culture vessel. 
The magnetic attraction between the guide strip and the scraper head is 
achieved either by the fact that both the guide strip and the scraper head 
have a magnet on their ends turned toward their respective counterparts, 
whose polarity attracts the other magnet (north pole/south pole, north 
pole/south pole), or by the fact that either the guide strip or the 
scraper head has a magnet and the respective counterpart contains a 
magnetizable material on its end turned toward the magnet. The scraper 
head can be made as a long part whose cross section can have, for example, 
the shape of a triangle or a rectangle with sides curved partially inward, 
so that the corners of this triangle simultaneously represent the cutting 
edges of the scraper head. Many other geometric cross-sectional shapes 
adapted to the shape of the respective cell culture vessel are also 
possible, which either offer a cutting edge themselves, or which make 
possible a fixed arrangement of a blade with a cutting edge. It is 
advantageous if the blade, in addition to functioning as a cutter or 
scraper, can simultaneously be made to function as a permanent magnet or 
to have a magnetizable material, the latter for the case that only the 
guide strip is provided with a magnet. The guide strip has a shape 
suitable for its function. 
Since metallic surfaces are toxic to cell cultures, the scraper head must 
be made from, or coated with, a plastic, non-toxic material. Preferably, 
both parts of the cell culture harvesting device, the scraper head and the 
guide strip, are coated with a plastic. This coating is non-toxic, and 
thus creates a surface which ensures optimal protection for the cell 
cultures, cell culture vessel parts, and operating personnel coming in 
contact with the cell culture harvesting device. In addition, the coating 
permits both the scraper head and guide strip to be moved with a minimum 
of friction against the growth surfaces and outside surfaces, 
respectively, of a cell culture vessel. Since, in principle, all tools 
coming in contact with the cell culture must be sterile, the plastic used 
for coating, especially that used for coating the scraper head, must be 
sterilizable by the common procedures (gamma rays, overpressure, gas, 
etc.) used to sterilize cell culture vessels. One plastic which fulfills 
these conditions is poly(tetrafluoroethylene) (PTFE), however, other 
plastics are also possible, such as polycarbonate, for example, and may 
also be utilized. 
Handling of the cell culture harvesting device is facilitated by the fact 
that the guide strip has a handle or, at least, gripping surfaces. The 
gripping surfaces may lie on the end of the guide strip opposite the 
magnet or the end having the magnetizable material. If desired, the 
gripping surfaces can be colored and/or ribbed. Alternatively, the guide 
strip can be installed or inserted in a table for setting cell culture 
vessels on, so that cell culture harvesting only requires moving a cell 
culture vessel with a scraper head back and forth on the surface of the 
table. 
To catch or collect the cells lifted off the growth surface of the cell 
culture vessel by moving the scraper head, the scraper head may optionally 
have a net-like container arranged on it. In a preferred embodiment, the 
container extends over the length of the scraper head and the opening of 
the container is at least as long as the cutting edge of the blade. This 
container is arranged on the upward-facing side of the scraper head while 
the container opening is adjacent to the cutting edge of the blade, so 
that the cells lifted off the growth surface by movement of the blade 
automatically collect in the collection container. In this manner, damage 
to the cells by distorting them or by touching the cells which are already 
resting loose on the growth surface of the cell culture vessel when a 
neighboring batch is harvested within the cell culture harvesting device 
is avoided. Furthermore, this collection container substantially 
facilitates the removal of the harvested cells. The outside dimensions of 
the collection container are naturally determined by the size of the 
openings in the cell culture vessel. 
Sample embodiments of the invention are explained in detail below using the 
drawings. FIG. 1a shows a simple embodiment of the invention. The scraper 
head 1 is shown positioned on the inside surface of a floor 2 from which 
cells are to be harvested. The floor 2 separates the scraper head 1 from 
its guide strip 3, which is made as a magnet. In this embodiment, the 
scraper head 1 has the shape of a long rod with a triangular cross 
section. Preferably, as shown, the sides 4 of the triangle are not 
straight but rather are curved inward, so that three possible cutting 
edges 5, 5', 5" result which are suitable to act as a blade. When the 
scraper head 1 is moved parallel to the floor 2 and perpendicular to one 
of the three cutting edges 5, 5', 5", the cells are lifted off the floor 2 
by the cutting edge. No additional blade is required in this design. In 
this embodiment, since all three edges are adapted to be a cutting edge, 
it does not matter which two of the three cutting edges 5, 5', 5" of the 
scraper head 1 are placed upon the floor 2. This feature demonstrates this 
design's simple and flexible manipulation. 
FIG. 1a also shows a rod-shaped magnet 6 in the center of the scraper head 
1, which extends inside over the entire length of the scraper head 1. This 
magnet 6 has its poles arranged so that a magnetic field is formed between 
it and the magnet or magnets (not shown here) inside the guide strip 3. 
The polarity of the magnets in the guide strip 3 is indicated by the 
letters N and S in FIG. 1a. The guide strip 3 is of the same length as the 
scraper head 1. Preferably, as shown, the guide strip has gripping 
surfaces 7 on the sides to facilitate gripping and moving of the guide 
strip. The illustrated guide strip 3 is shown having a rectangular shape, 
however, it will be appreciated that any shape may be used so long as 
stable and secure magnetic attraction is maintained with the entire length 
of the scraper head, which may also have different shapes, as described 
below. 
FIG. 1b shows several scraper heads 1 with different geometries on the 
floor 2 of a cell culture vessel. The selection of geometry is guided by 
the respective shape of the cell culture vessel in which the scraper head 
will be used. A scraper head 1 having a triangular profile is suitable for 
a roller bottle, as shown in FIG. 2. This design makes it possible, 
without special effort, to harvest all cells on the lateral surface of the 
roller bottle by moving the scraper head 1 with a guide strip lying 
outside against the roller bottle. 
The cell culture harvesting device shown in FIG. 3 describes an embodiment 
which has been expanded by adding a collection container 8. The scraper 
head 1 is represented by the blade 9 with only one cutting edge 5'". Blade 
9 may be a permanent magnet or may consist of magnetizable material. The 
upward side of blade 9 has a net-like collection container 8 arranged on 
it. The collection container 8 has an opening 10 directed toward the 
cutting edge 5'". The mesh size of the net-like collection container 8 is 
preferably in the range of about 1-20 .mu.m, depending on the type of cell 
to be harvested. Moving the scraper head 1, which is in the form of the 
blade 9 and which is equipped with the collection container 8, in the 
direction of the arrow, parallel to the floor 2 and perpendicular to the 
cutting edge 5'", effects collection of the lifted cells 11--represented 
here as irregular, round particles--within the collection container 8. 
Scraper head 1 is moved by operating the guide strip 3, which is separated 
from the scraper head 1 by the floor 2, and which has all the same 
features as the guide strip 3 in FIG. 1a. 
FIG. 4 shows a scraper head 1 that is held in a stable and secure position 
within the cell culture vessel by a holder 12 located inside a cell 
culture vessel at the edge of the floor 2. Here, the scraper head 1 has a 
cylindrical geometry, with an inward curved lateral surface. The holder 12 
consists, for example, of two elastic plastic wings, which are adjusted at 
such at an angle to one another starting from the edge of the floor 2 that 
they limit and hold the scraper head 1. When a guide strip 3 (as shown in 
FIG. 1) is placed directly opposite the scraper head on the outside of the 
floor 2, the scraper head 1 is ready to be moved due to the magnetic 
attraction. Because of the elasticity of the holder 12, the scraper head 1 
is readily released from the position within the holder when the scraper 
head 1 is caused to move synchronously with the movement of the guide 
strip 3. 
The present invention may be embodied in other specific forms without 
departing from its spirit or essential characteristics. The described 
embodiments are to be considered in all respects only as illustrative and 
not restrictive. The scope of the invention is, therefore, indicated by 
the appended claims rather than by the foregoing description. All changes 
which come within the meaning and range of equivalency of the claims are 
to be embraced within their scope.