Biomagnetic separation attracts diagnostics, DNA transfer and cancer
27 May 2011
A brief history of biomagnetic separation
The principle behind magnetophoresis is the action of a magnetic
force on particles. Even a simple block magnet can exert some degree
of force onto a nearby test-tube. The process of refining this with
improved orientation of the magnets and fluid (which is to be
separated) and numerical algorithms has lead to SEPMAG, a
specialized company, being formed and producing commercial magnetic
separation products with a wide range of applications within the
In becoming the successful and promising tool that biomagnetic
separation is now widely seen as, a number of obstacles had to be
overcome. The maximum capacity manufactured by IVD companies using
the previous generation of biomagnetic separators was around 50ml:
well below the several litres often required for manufacturing
processes and the widely used Chemoluminescence Immunoassays (CLIA).
Further concerns were raised by the safety of these machines,
since there had been reported injuries and the problems caused by
having to remove pacemakers, computers or magnetic recording devices
from around a large surrounding area, because of possible magnetic
interference. These obstacles presented significant challenges to
the development of bio-magnetic separation, such that non-magnetic
separation research became increasingly popular in the hope of
providing a realistic alternative.
These challenges were addressed in 2004, through discussions
generated by the collaboration between ATIPIC and BIOKIT; and
resulted in successful and intrinsically safe scaling up of the
process and a reduced separation time (to one order of magnitude).
This impressive work was further built upon by subsequent
dialogues between a number of global-reaching IVD companies such as
Bio-Rad, Biocode, Diasorin and Roche Diagnostics. The major change
resulting from this was in the definition of the bio-magnetic
separation process, since analysis of the process was now available
using a range of parameters.
Defining the operating conditions in addition to separation time
provided additional support for developing SOP (standard operating
procedure) and Quality Assurance protocols, which are both important
milestones in a products journey to the market place.
Background to SEPMAG
The potential of this technique within the biotechnology and
biomedical industry is demonstrated by the decision taken by Dr Luis
M. Martinez to purchase the patent of the product resulting from
international discussions in 2007 and form a company specialising in
this area, SEPMAG.
The devices that SEPMAG subsequently produced enabled the study
of the dynamics of colloidal suspension, thanks to the homogeneous
conditions provided by this new generation of bio-magnetic
separation devices. Another consequence of this technology was the
generation of new theoretical magnetic colloidal models to explain
the greatly reduced separation times seen experimentally with the
SEPMAG was in a position to capitalise on the numerous benefits
of bio-magnetic separation, and in early 2011, secured a Chinese
Patent for its unique homogenous biomagnetic separation process from
China’s State Intellectual Property Office (SIPO). They have since
entered the Chinese market and shipping of the SEPMAG Q250ml product
to CapitalBio began in January. CapitalBio is a leading Chinese
company, which has recently begun a partnership with Roche
Diagnostics. Because of the advantages of bio-magnetic separation
over the market alternative, ELISA (Enzyme-Linked ImmunoSorbent
Assays), it is hoped that acquiring this strategically significant
client is part of a growing trend in the uptake of SEPMAG’s products
in both the Chinese and global markets.
Josep Maria Simó, CEO of SEPMAG, commented: “We are delighted
that the Chinese Patent Office has granted SEPMAG a patent for our
unique magnetophoresis techniques. This will allow us to further
consolidate our Far-East presence, having already established a
strong and growing foothold in Japan. Over the next couple of years,
we forecast the Chinese marketplace to be amongst the fastest
growing for bio-magnetic separation systems. The agreement we have
signed with CapitalBio marks the start of a significant expansion in
the region and a continuation of the internationalisation of SEPMAG
To bring the advantages of bio-magnetic specification to the
wider biotechnology industry, SEPMAG has been working with
theoretical physicists developing ‘precision magnetophoresis’ to
enable the application of the technology to a wide range of specific
uses across the industry.
Current uses of BMS
Those benefiting today from these developments in the field of
BMS are from a broad range of specialities within the biotechnology
industry. They do however fall into two rough categories; those
using it for in vitro procedures and those applying it to
in vivo scenarios.
The in vitro applications
fall into 4 categories , all of which are in frequent use across
- Immuno and molecular diagnostics:
Bio-magnetic separation increased [2, 3, 4]) or DNA can be
captured and separated from a sample. The process is also easy
to automate and as a result some diagnostic companies have
developed their own analysers for the process.
- Protein purification: Capture of specific
proteins can be achieved in the face of high exposure levels and
the presence of particulates. Immobilisation of beads with
magnetic forces makes it possible to concentrate and purify the
selected protein . Because the filtration, centrifugation and
clarification stages of conventional separation are not needed
when separating using magnets, more protein can be recovered
from the original suspension than is possible using conventional
methods. This purification allows for downstream processing,
used commonly in pharmaceutical development and production.
- Cell capture: Using crude samples such as
blood, bone marrow, tissue homogenates, stool, cultivation
media, food, water and soil, BMS can capture specific cell types
. There are two possible methods of capturing cells:
- Using high magnetic forces (magnetic columns) with cells
that have adequate intrinsic magnetic moment (namely
erythrocytes with high concentrations of paramagnetic
haemoglobin and magnetotactic bacteria);
- Using permanent magnet devices and labels for all other
cell types. These magnetic components are able to interact
with the cell surface via high affinity ligands;
- The capture of specific cells then opens the doors for
further investigation or diagnosis ; for example,
cultivation of cells or analysis of intercellular components
(by lysis of the cell) — since it is possible to remove the
magnetic label if needed.
- Nucleic acids capture: BMS can be used to
collect all the nucleic acids (DNA or RNA) in a suspension,
using silica magnetic beads. This precedes the separation of
specific nucleic acid sequences using magnetic beads attached to
the correct complimentary DNA strands. The BMS technique
provides an effective alternative to the time-consuming PCR
step, thus opening the doors to further DNA research.
The benefits of BMS
The benefits of bio-magnetic separation are six-fold. The systems
operate such that there are high degrees of reproducibility for
every single diagnostic test (an essential factor in any scientific
experiment or test). The scale up of operations is easy, which
simplifies any revalidation processes.
Process monitorisation allows any problems (for example bead size
distribution, concentrations and buffer conditions) to be detected
earlier, which avoids the production of defective batches and
increases the efficiency of the system. Safe operation is achieved
with minimal stray magnetic fields, with the additional bonus of
saving space in the lab by reducing the caution distance of
operation to a few centimetres.
The time taken for the separation process is reduced, taking the
separation time down from hours to seconds and without the need for
excessive force — which generates additional problems. Further gains
are made financially by the minimal loss of beads and precious
bio-molecules through the process; up to 20% savings have been
reported by some companies.
Future and potential applications of BMS
The hardware developed by SEPMAG opens the door to the potential
application of this technology in a host of laboratory and clinical
settings. A lot of this potential lies in its in vivo
Building on the nucleic acid capture already in use, the transfer
of nucleic acids (as foreign genetic material) into cells is being
researched. Using magnetic forces that act on molecules attached to
the nucleic acids directs them towards targeted cells. This can
increase the transgene expression levels by up to three orders of
magnitude from the normal method, increasing the efficiency of the
process. This has potential applications in bacteriology,
pharmaceutical R&D and genetic studies.
The conditions for viral-mediated gene delivery (an alternative
mechanism of DNA transfer) may be optimised by combining the viral
vectors with magnetic particles. This allows the viral dose and
exposure to be reduced, which in turn reduces the chance of any side
Magnetic separation technology has further roles in the delivery
of biological compounds, including pharmaceutical molecules. If
associated with magnetic nanoparticles, therapeutic agents can be
targeted to direct sites in the body . This overrides the need
for ligand-based drug delivery, the problems of which are twofold.
Firstly, specific receptors may not be 100% specific, causing
additional side effects and secondly, identifying these receptors
can be a challenge, often creating impassable obstacles for
conventional drug delivery.
Magnetically-mediated hyperthermia  (MMH) is a possible
physical therapy for cancer, based on the principles of heating
tumour cells to above 43 degrees to kill them. Current
hyperthermia-inducing methods are limited by their inability to be
localised to an appropriate degree. However, magnetic forces can be
used to accumulate magnetic particles in a localised region of
The accumulated magnetic particles are then subjected to an
alternating magnetic field and heat up, killing the surrounding
tumour cells. The selectivity of this treatment lies in the fact
that cancer cells are less heat-resistant than normal cells. This
specificity is associated with reduced side effects and it would
then be possible to use this alongside conventional cancer therapy
(such as chemotherapy and radiotherapy).
Tissue engineering is a rapidly expanding new dimension of modern
medicine, and magnetic-force based tissue engineering  — which
uses the same magnetic forces of BMS — is at the heart of it.
Labelling cells magnetically allows them to be organised into 2D and
3D multi-layered structures using magnetic forces. Studies have
already used it for a range of tissues from umbilical veins to
retinal pigment epithelial cells and keratinocytes to mesenchymal
stem cells. These functional substitutes could one day be used in
the clinic to replace lost or damaged tissues.
The parameterisation of the bio-magnetic separation process
allows for optimisation of the process, which in turns opens the
doors for its application to a wide range of clinical and laboratory
processes. In the last decade this technology has improved
unrecognisably and has been applied to an enormous range of
situations. With the current research on in vivo applications, it is
an exciting time for biomagnetic separation and the large number of
specialities, companies and patients that look to benefit from it.
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