See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/338988209

ELECTROPHORESIS APPLICATIONS USED IN MEDICINE

Article  in  e-Journal of New World Sciences Academy · January 2020

DOI: 10.12739/NWSA.2020.15.1.1B0086

CITATIONS READS

0 8,707

2 authors:

Ozlem Demir Coşkun Ozlem Oztopuz

Canakkale Onsekiz Mart University Faculty of Medicine Çanakkale Onsekiz Mart Üniversitesi
21 PUBLICATIONS   169 CITATIONS    22 PUBLICATIONS   40 CITATIONS   

SEE PROFILE SEE PROFILE

Some of the authors of this publication are also working on these related projects:

DETERMINATION OF IL-6,TNF-ALPHA AND VEGF LEVELS IN THE SERUMS OF PATIENTS WITH COLORECTAL CANCER View project

Tubitak View project

All content following this page was uploaded by Ozlem Demir Coşkun on 06 February 2020.

The user has requested enhancement of the downloaded file.

 Medical Sciences Status : Review
ISSN: 1308-7312 (NWSAMS) Received: 07.06.2019
ID: 2020.15.1.1B0086 Accepted: 15.10.2020

Özlem Coşkun, Özlem Öztopuz

Çanakkale Onsekiz Mart University, Çanakkale-Turkey
ozlemcoskun@comu.edu.tr; ozlemoztopuz@comu.edu.tr

DOI http://dx.doi.org/10.12739/NWSA.2020.15.1.1B0086
ORCID ID 0000-0002-0741-5001 0000-0002-1373-6311
CORRESPONDING AUTHOR Özlem Coşkun

ELECTROPHORESIS APPLICATIONS USED IN MEDICINE

ABSTRACT
Clinical analysis distinguishing between the characteristics of
healthy and pathological conditions, the researcher to solve the mystery
of the disease and to provide the treatment of the disease in a short
time is very important to save human life. Electrophoresis routine
biochemistry, hematology, or urinalysis is one of the basic diagnostic
methods commonly used in the world to obtain vitally important
information. Nonspecific changes in electrophoretic patterns are
associated with patient clinical data electrophoresis, it is very
valuable in determining the diseases which cannot be detected by routine
diagnostic studies. Many diseases such as liver, renal pathological
disorders, inflammation, proteinemia, multiple myeloma, and
macroglobulinemia can be diagnosed by electrophoresis. Recent
developments in electrophoresis technology will be the miniaturization
and portability of systems. With the development of technology, it is
possible to perform electrophoresis with programming that enables
automatic execution of computerized robotic and electrophoresis
protocols. Large research is carried out to improve the systems used by
different working groups, especially the automatic electrophoresis
system. The methods explored and developed are mainly aimed at increasing
the efficiency, reproducibility and accuracy of the separation process.
The aim of this review is to emphasize the general features of
electrophoresis method, clinical diagnostic applications and future
potential.
Keywords: Electrophoresis, Electrophoresis in Diagnosis,
Clinical Applications, Clinical Analysis,
Electrophoresis Types

1. INTRODUCTION
Clinical analysis is very important in terms of improving the
quality of life by providing rapid medical treatment [1]. In order to
solve the problems encountered in clinical medicine, clinical analyzes
should be performed by experts to obtain accurate results at the lowest
possible cost. Numerous electrophoretic methods are routinely used in
various clinical laboratory [2]. Electrophoresis is a sort of separation
technique based on the differential migration properties of charged
molecules in an electric field. It is an analytical method commonly used
in molecular biology, biochemistry and medicine [3]. For qualitative and
preparatory purposes, electrophoretic methodologies are widely used in
biological research and are well defined in most research laboratories
as a long-term integral analytical tool [4]. Electrophoretic methods are
important applications used in the identification of many diseases
including biochemistry, gene technology, nucleic acid and protein
sequencing, cancer in recent years. Electrophoresis is a common technique
used in almost any field of basic or applied biomedical research for

How to Cite:
Coşkun, Ö. and Öztopuz, Ö., (2020). Electrophoresis Applications Used in Medicine,
Medical Sciences (NWSAMS), 15(1):12-25, DOI: 10.12739/NWSA.2020.15.1.1B0086.
 Coşkun, Ö. and Öztopuz, Ö.,
Medical Sciences (NWSAMS), 1B0086, 2020; 15(1):12-25.

separation by charge and/or mass. In electrophoresis, molecules such as

proteins, enzymes, lipoproteins are separated using various support
media (paper, cellulose acetate, starch, agarose and polyacrylamide)
depending on the type of electrophoresis. Factors affecting mobility are
the size, shape, ionic strength of the solution, viscosity and
temperature of the medium [5 and 6]. Electrophoresis is frequently used
to identify diseases that cannot be detected by routine diagnostic
studies, and to identify and follow pathological conditions.
Electrophoretic patterns, routine biochemistry analysis, hematology
applications or urine analysis, especially in the separation of serum
proteins have been widely used in medicine for many years [7]. Evaluation
of serum proteins and their electrophoretic models are well-established
laboratory method for the diagnosis, pathological detection and
monitoring of many diseases. The results of serum protein electrophoresis
are one of the most useful diagnostic pathways in a wide range of
diseases, including infectious and inflammatory diseases, renal or
gastrointestinal disorders, immunodeficiency states as well as
paraproteinases caused by lymphoid or neoplasia [8]. Since the
incorporation of electrophoresis into the scientific field, many changes
and improvements have been made to the system in terms of analysis and
efficiency. From basic paper electrophoresis to highly advanced
automatic microchip electrophoresis system, each different system has
its own unique functionality and unique application. With the development
of technology, it is possible to perform electrophoresis with programming
that enables automatic execution of computerized robotic and
electrophoresis protocols [9].

2. RESEARCH SIGNIFICANCE
Electrophoresis is a widely used technique based on the use of
electric current in diagnosis and biomedical research. Today, many
electrophoresis techniques are used for routine or research purposes.
Electrophoresis detection of many diseases that cannot be detected by
routine diagnostic methods makes the method even more important. This
review provides information about some electrophoresis techniques used
in medicine. The advantages of recent developments in electrophoresis
technology have been evaluated with current literature.

3. SOME ELECTROPHORESIS TYPES USED IN CLINIC

Some electrophoresis methods used in clinical investigations are
summarized in the table.

Table 1. Electrophoresis Types Used in Clinic

Electrophoresis Types Clinic Applications References
Polyacrylamide Gel Abnormal Serum or Urine Protein 10
Electrophoresis
Agarose Gel Electrophoresis Serum Proteins, Hemoglobin Variants, 13
Isoenzymes, Lipoprotein Fractions
Pulsed-Field Gel Chromosomal DNA, Many Bacterial 19-21
Electrophoresis Species Causing Diseases,
Antimicrobial Susceptibility Testing,
Serotyping and Genome Sizes
Isoelectric Focusing Monoclonal Antibody 24
Two Dimensional Proteomics 28
Electrophoresis
Capillary Electrophoresis Genomic And Pharmaceutical Fields 38
Microchip Electrophoresis Genotyping, Mutation Analysis, 41
Immunological Tests
Immunoelectrophoresis Immunoglobulin 45
Immunofixation Monoclonal Immunoglobulin 48
Electrophoresis
Hemoglobin Electrophoresis Hemoglobin Variants 49

13
 Coşkun, Ö. and Öztopuz, Ö.,
Medical Sciences (NWSAMS), 1B0086, 2020; 15(1):12-25.

3.1. Polyacrylamide Gel Electrophoresis (PAGE)

Polyacrylamide Gel Electrophoresis is the most common type of
electrophoresis. It is a low-cost, reproducible and rapid method for
quantifying, comparing and characterizing protein, peptides and small
molecular weight nucleic acids [10]. Separation of the gel power and
molecular weight depend on the acrylamide/bisacrylamide ratio.
Polymerization of these two substances creates pores in the gel (Figure
1). PAGE is used to control the purity of proteins, determination of
molecular weights and concentration [11].

Figure 1. Polyacrylamide Gel Electrophoresis [12]

3.2. Agarose Gel Electrophoresis (AE)

Agarose gel electrophoresis has been successfully applied for the
analysis of serum proteins, hemoglobin variants, isoenzymes, lipoprotein
fractions. It is usually used to separate DNA or RNA fragments of
different lengths (Figure 2). In this method, molecules are separated
according to their length, size and structure [13]. Agarose gel
electrophoresis is widely used in various fields of biotechnology,
biomedical and forensic laboratories. It is also a technique used
routinely in clinical laboratories to detect protein abnormalities in
various biological fluids (serum, urine, cerebrospinal fluid) [14].

Figure 2. Agarose Gel Electrophoresis [15]

14
 Coşkun, Ö. and Öztopuz, Ö.,
Medical Sciences (NWSAMS), 1B0086, 2020; 15(1):12-25.

3.3. Pulsed-Field Gel Electrophoresis (PFGE)

DNA molecules of large molecular weight cannot be separated by
classic electrophoresis. PFGE separates chromosomal DNA from many living
species utterly, including bacteria, viruses and mammals, from the
parasite chromosome to the yeast chromosome [16-18]. The most significant
difference of PFGE from other electrophoresis techniques is that the
applied electric field is not constant (Figure 3). PFGE is used for
characterization of many bacterial species causing diseases,
antimicrobial susceptibility testing, serotyping and genome sizes [19-
21].

Figure 3. Schematin presentation of Pulsed-Field Gel

Electrophoresis [22]

3.4. Isoelectric Focusing (IEF)

Isoelectric focusing is based on the separation of proteins
according to isoelectric points. In this method, the pH gradient is
formed by low molecular weight ampholites. In the gel, a decreasing pH
gradient occurs from the anode to the cathode (Figure 4). Proteins
migrate to a pH (pI=isoelectric point) where the net charge on the gel
is zero and stop at this point [23 and 24].

Figure 4. Isoelectric focusing [25]

15
 Coşkun, Ö. and Öztopuz, Ö.,
Medical Sciences (NWSAMS), 1B0086, 2020; 15(1):12-25.

3.5. Two-Dimensional (2DE) Gel Electrophoresis

Two-dimensional polyacrylamide gel electrophoresis (2-DE) is
considered to be a powerful tool for separating complex protein mixtures
from tissues, cells or other biological samples. With this method,
hundreds of thousands of proteins are separated in a gel [26]. Two-
dimensional electrophoresis makes it possible to obtain important
diagnostic information from hundreds of possible protein peaks. This
method uses IEF (isoelectric focusing) in the first dimension. In the
second dimension, molecular weight-dependent SDS-PAGE(Sodium Dodecyl
Sulfate-Polyacrylamide Gel Electrophoresis) is used (Figure 5) [27]. In
this method, computer support is needed in order to interpret or compare
the points indicating the presence of a large number of proteins on the
gel after staining. A complete disease diagnosis can be obtained by
analyzing proteins present in both normal and diseased cells or tissues.
Proteomics defines the structure, location, amount, post-translational
modifications, functions of tissues and cells of all proteins and their
interaction with other proteins and macromolecules. It is the main method
for proteomics. With this method, even small changes in protein amounts
can be analyzed. Thus, new proteins that arise in pathological conditions
can be readily identified. The comparison can be made between two
different situations (normal and disease, old and young) with expression
proteomics [28]. 2D is used for profiling in proteiomics studies, and
the most important function of this method is the different
representations of proteins expressed in different conditions(Figure 5).

Figure 5. Two-Dimensional (2DE) gel electrophoresis [29]

Many research has been done on the biological and clinical

applications of proteomics[30].Proteomic technology is used to
systematically analyze and quantify the relationships, structure and
function of proteins in cells, tissues and body fluids in different
conditions such as health and disease [31]. The goals of proteomics
studies include early diagnosis of diseases, identification of different
stages, and the development of new and effective biomarkers for better
evaluation of therapeutic applications. The characteristics of an ideal
biomarker should be specific for a particular disease, enable early
diagnosis of this disease, change in the amount of disease development
and change, allow the follow-up of the drug treatment, work on easily
obtainable biological material, and repeatable and easily applicable
method (Figure 6) [32].

16
 Coşkun, Ö. and Öztopuz, Ö.,
Medical Sciences (NWSAMS), 1B0086, 2020; 15(1):12-25.

Figure 6. Applications of Two-Dimensional (2DE) Gel Electrophoresis

[33]

3.6. Capillary Electrophoresis (CE)

The capillary electrophoresis technique and equipment are quite
different from other electrophoresis techniques. The system consists of
a thin silica capillary tube, two electrolyte buffer chambers, a high
voltage power supply and a detector associated with a data evaluation
unit (Figure 7). The advantage of working in narrow diameter tubes is
the elimination of heat generated by other electrophoretic methods [34
and 35]. Capillary electrophoresis is an analytical technique used for
the separation and quantification of a wide variety of molecules based
not only on charge but also on size, hydrophobicity and stereospecificity
[36]. Capillary electrophoresis is an analytical method used in genetic
analysis, drug discoveries, analysis of drug impurities, including anti-
cancer drugs, and protein characterization [37]. The clinical advantage
of capillary electrophoresis is that application, flexibility and the
ability to analyze compounds of diagnostic importance. This technique
allows rapid and low sample volume funtion in clinical laboratories in
genomic and pharmaceutical fields, and has the advantage of being
quantitative and automated as well as separating compounds that are
difficult to distinguish by conventional methods [38].

Figure 7. Capillary Electrophoresis [39]

3.7. Microchip Electrophoresis (ME)

Microchip electrophoresis systems are superior to other systems
because they contain a large number of microchannels that allow the

17
 Coşkun, Ö. and Öztopuz, Ö.,
Medical Sciences (NWSAMS), 1B0086, 2020; 15(1):12-25.

experiments to be carried out quickly and efficiently. It is also a

fully automated system that allows minimum manuel use from sample
processing to data analysis [40]. Since highly sensitive methods are
required for ME, laser-induced fluorescence and electrochemical
detection methods are used. Its superiority over other techniques is
better heat dissipation, automation, speed, flexibility and simplicity.
The key element in clinical diagnosis is the interpretation of the data
obtained by analysis of patient samples. Although standard clinical
diagnostic methods require days to retrieve patient data, ME can reduce
outcome up to minutes, accelerating the transition to treatment (Figure
8). Microchip eletrophoresis has been widely used in clinical diagnosis
for genotyping, mutation analysis, immunological tests and small
molecule detection. This technique is used in the diagnosis of diseases
such as cancer, immune disorders, neurological diseases, genetic
disorders, cardiovascular diseases, infectious diseases and pathogens,
organ and functional disorders, diabetes and pancreatic dysfunction and
reproductive disorders. It has been reported that ME provides high-speed
analysis with minimum sample for both patients and clinicians in the
diagnosis in the last decade [41].

Figure 8. Microchip Electrophoresis [42]

3.8. Immunoelectrophoresis (IF)

Serum protein electrophoresis is widely used for the detection and
identification of paraproteins, as well as changes in proteins associated
with inflammation, liver or kidney disease in clinical laboratories
[43].It is used for the diagnosis and follow-up of paraproteinemias.
Both protein concentration changes and structural abnormalities can be
detected by immunoelectrophoresis, which shows monoclonal protein
production in serum protein electrophoresis (Figure 9).
Immunoelectrophoresis analysis involves two consecutive procedures. 1-
Separation of proteins in the mixture by agarose gel electrophoresis 2-
Antiserum added to the separated protein to show antigen antibody
precipitates. Antigen-antibody precipitation bands are formed after
simultaneous diffusion. The structure and position of the precipitation
bands is characteristic for each protein, compared with control sera
[44].

18
 Coşkun, Ö. and Öztopuz, Ö.,
Medical Sciences (NWSAMS), 1B0086, 2020; 15(1):12-25.

Figure 9. Serum immunoelectrophoresis showing the immunoglobulin

G kappa monoclonal band [45]

3.9. Immunofixation Electrophoresis (IFE)

Immunofixation electrophoresis is a gold standard biochemical
technique used to guide the diagnosis, follow-up and treatment of
monoclonal gamopathies. IFE is a preferred method for the diagnosis and
follow-up of multiple myeloma, paraproteinemias in medical research,
genetic studies and clinical laboratory applications (Figure 10).
Immunofixation electrophoresis is a two-stage;
 Step 1: Separation of proteins in agarose gel
 Step 2: Immunosuppression; serum, urine, CSF (cerebrospinal fluid)
or other body fluids can be used [46].
The presence of a monoclonal protein detected in serum protein
electrophoresis, an indeterminate narrow band, hypogammaglobulinemia,
increased beta or gamma fraction is considered abnormal. In this case,
serum and urine IFE assessment is required to confirm and identify the
monoclonal protein.

Figure 10. Immunofixation electrophoresis(IFE) on serum from 4

patients[47]

19
 Coşkun, Ö. and Öztopuz, Ö.,
Medical Sciences (NWSAMS), 1B0086, 2020; 15(1):12-25.

Since immunofixation can be used for the identification and typing

of monoclonal immunoglobulins, it has replaced the usual
immunoelectrophoresis in many laboratories. The reason why IFE is widely
used compared to immuno-electrophoresis is related to the many advantages
it provides in the process stage. IFE helps to make a more accurate
conclusion about doubtful cases that cannot be clearly identified by
normal protein electrophoresis. Changes in serum proteins may be
indicative of nonspecific pathological processes or may represent
potential diagnostic markers of certain pathological conditions [48].

3.10. Hemoglobin Electrophoresis (HE)

Hereditary abnormalities encountered in hemoglobin synthesis are
grouped under two main groups. These are abnormal hemoglobin variants
and thalassemia (Figure 11). Hemoglobin electrophoresis is used to
identify anomalies. HB electrophoresis is very easy, sensitive and fast
method in pH: 8.5 using agarose gel with cellulose acetate membrane in
routine analysis.

Figure 11. Hemoglobin electrophoresis [49]

3.11. Automatic Electrophoresis System

With the development of technology, it is now possible to perform
electrophoresis using programs that provide computerized robotic
electrophoresis systems [50]. High efficiency protein analysis can be
performed with automatic 2D capillary electrophoresis system. In the
Human Genome Project, an automated electrophoresis system was used to
detect changes in the human gene. Automated electrophoresis systems are
extremely sensitive to detect conformation polymorphism in genetic
samples. High efficiency protein analysis can be performed with automatic
2D capillary electrophoresis system. In the Human Genome Project, an
automated electrophoresis system was used to detect changes in the human
gene. Automated electrophoresis systems are extremely sensitive to
detect conformation polymorphism in genetic samples [51 and 52]

3.12. Future Electrophoretic Developments

With the development of technology, it is possible to increase the
speed and processing of the electrophoresis using fewer samples. Although
electrophoresis technology is very advanced from the traditional
electrophoresis system to the microchip electrophoresis system, an
external power supply is still needed for electrophoresis [53).
Electrophoresis without a power supply is not possible yet. Numerous
patents have been received to improve efficiency with existing systems,

20
 Coşkun, Ö. and Öztopuz, Ö.,
Medical Sciences (NWSAMS), 1B0086, 2020; 15(1):12-25.

such as using a different buffer system or gel type [54]. Research is

continuing to improve the systems currently used by different research
groups around the world, in particular the automatic electrophoresis
system [55].

4. DISCUSSION
Electrophoretic techniques will continue to be applied in the
clinical laboratory for many years. It will become increasingly important
to select and apply the appropriate electrophoresis technique for
specific separation problems. High-resolution electrophoretic methods
can be applied to solve heterogeneous clinical problems and simplify the
analytical process by fully automated electronic handling of data.
Capillary electrophoresis is the best automation solution for all
electrophoresis methods to detect nucleic acids by electrophoretic
mobility. In addition to size characteristics, fluorescent labels give
DNA fragments another feature for identification. CE, which requires
minimal human intervention from sample loading to data analysis, not
only saves a lot of labor, but also eliminates most human errors related
to sample loading, data analysis and input. With capillary
electrophoresis, great attention to detail, such as capillary location
and gas flow rate of each test run, should be taken to reproduce the
same results, as differences in settings will produce different results
for the same experiment [56]. SDS polyacrylamide gel electrophoresis has
proved to be an incredibly useful analytical method for determining the
number and size of polypeptides in a sample. It has the ability to
dissolve many individual proteins when done skillfully [57]. The
potential to integrate many functions into a single device, minimal
sample and reagent consumption, and the ability to analyze a wide variety
of molecules make microchip electrophoresis an ideal candidate for next-
generation separation technology that has an impact on a variety of
aspects, including the pharmaceutical industry [58]. The combined use
of many powerful new techniques makes the analysis of mammalian genes
within reach. PFGE will play an important role in mapping the human
genome. The PFGE technique will be useful to determine the degree of
association between different strains of the same species. PFGE
techniques for future applications may include separation of protein and
nucleic acid sequences and DNA topology studies. PFGE allows physical
mapping for almost all organisms [59]. Finally, Microchip
electrophoresis is a promising new electrophoresis technology developed
and tested for the detection of biomarkers in clinical specimens such
as urine, serum, cerebrospinal fluid and saliva. For all that, microchip
electrophoresis evolved from capillary electrophoresis, a promising
miniaturization technology that is considered a hybrid form of
electrophoresis and chromatography [60 and 61]. Electrophoresis is one
of the most common techniques used for analytical and pharmaceutical
separations. Electrophoresis technique is used in research and applied
biomedical studies. Electrophoresis distinguishes clinically
abnormalities such as dysproteinemia and paraproteinemia, it is also
possible to identify physiological electrophoretic patterns in specific
laboratory studies and to distinguish healthy ones. Thanks to this
technique, there have been revolutionary developments in the detection
and epidemiology of infectious diseases in recent years.

5. CONCLUSION
The development of electrophoresis systems is driven by advances
in technology and also by the necessity of better and faster resolution
of the results. Electrophoresis technology began at the beginning of the
nineteenth century and is still in practice even after two centuries.
Although the existing electrophoresis, equipment and style are performed

21
 Coşkun, Ö. and Öztopuz, Ö.,
Medical Sciences (NWSAMS), 1B0086, 2020; 15(1):12-25.

in many different ways and methods, which are very different from the
original design, the basic principle remains the same. Following the
trends of changes in electrophoresis technology, the next step of
development will be miniaturization and portability of systems.

NOTICE
This study was presented as an oral presentation in the
“International Hippocrates Congress on Medical and Health Sciences (1-3
March 2019 Ankara/Turkey” and restructured.

REFERENCES
[1] Gostin, L.O., Levit, L.A., and Nass, S.J., (Eds.) (2009). Beyond
the HIPAA Privacy Rule: Enhancing Privacy, Improving Health
Through Research. National Academies Press.
[2] Tissot, J.D., Layer, A., Schneider, P., Forestier, F., and
Henry, H., (2000). Gel Electrophoresis.
[3] Caballero, B., Trugo, L.C., and Finglas, P.M.,
(2003). Encyclopedia of Food Sciences and Nutrition. Academic.
Burgess, R.R. and Deutscher, M.P., (Eds.) (2009). Guide to
Protein Purification (Vol:463). Academic Press.
[4] Fesmire, J.D., (2019). A Brief Review of Other Notable
Electrophoretic Methods. In Electrophoretic Separation of
Proteins (pp:495-499). Humana Press, New York, NY.
[5] Gowenlock, A.H., McMurray, J.R., and McLauchlan, D.M., (1987).
Separative Procedures, Electrophoresis. In: Varley’s Practical
Clinical Biochemistry. Heinman Medical Books, London. 69-81.
[6] Marshal, W.J., (1995). Clinical Chemistry. Mosby, London. 201-
12.
[7] Vavricka, S.R., Burri, E., Beglinger, C., Degen, L., and Manz,
M., (2009). Serum Protein Electrophoresis: an Underused but Very
Useful Test. Digestion, 79:203-10.
[8] Tothova, C., Nagy, O., and Kovac, G., (2016). Serum Proteins and
Their Diagnostic Utility in Veterinary Medicine: A Review.
Veterinarni Medicina, 61:475–496.
[9] Chin, K.J., Yuen, K.H., Sieo, C.C., and Yiap, B.C., (2013).
Electrophoresis: What does a Century Old Technology Hold for the
Future of Separation Science?.
[10] Judd, R.C., (1996). SDS-polyacrylamide Gel Electrophoresis of
Peptides. In The Protein Protocols Handbook (pp:101-107).
[11] Laemmli, U.K., (1970). Cleavage of Structural Proteins during
the Assembly of the Head of Bacteriophage T4. Nature., 227:680–
685.
[12] Jalali, M., Saldanha, F.Y.L., and Jalali, M., (Eds.)
(2017). Basic Science Methods for Clinical Researchers. Academic
Press.
[13] Hames, B.D., (1998). Gel Electrophoresis of Proteins A Practical
Approach Third Edition. Edited by School of Biochemistry and
Molecular Biology.
[14] Giot, J.F., (2010). Agarose gel Electorphoresis–applications in
Clinical Chemistry. JMB., 29:9–14.
[15] Drabik, A., Bodzoń-Kułakowska, A., and Silberring, J., (2016).
Gel Electrophoresis. In Proteomic Profiling and Analytical
Chemistry (pp:115-143).
[16] Nedelcu, S. and Watson, J.H.P., (2004). Size Separation of DNA
Molecules by Pulsed Electric Field Dielectrophoresis. J. Phys.
D: Appl. Phys., 37:2197–2204.
[17] Schwartz, D.C. and Cantor, C.R., (1984). Separation of Yeast
Chromosome-sized DNAs by Pulsed Field Gradient Gel
Electrophoresis. cell, 37(1):67-75.

22
 Coşkun, Ö. and Öztopuz, Ö.,
Medical Sciences (NWSAMS), 1B0086, 2020; 15(1):12-25.

[18] Gardiner, K., (1991). Pulsed Field Gel Electrophoresis.

Analytical Chemistry., 63:658-665.
[19] Tejedor, J.L., Vela, A.I., Gibello, A., Casamayor, A.,
Dominguez, L., and Fernandez, J.F., (2011). A Genetic Comparison
of Pig, Cow and Trout Isolates of Lactococcus garvieae by PFGE
Analysis. Letters in Applied Microbiology., 53:614–19.
[20] Türe, M. and Altınok, İ., (2013). Pulsed-Field Jel Elektroforez
(PFGE) Metodu ve Akuatik Organizmalarda Kullanımı. Süleymen
Demirel Üniversitesi Eğirdir Su Ürünleri Fakültesi Dergisi.,
9:44-54.
[21] McEllistrem, M.C., Stout, J.E., and Harrison, L.H. (2000).
Simplifield Protocol for Pulsed-Field Gel Electrophoresis
Analysis of Streptococcus pneumoniae. Journal of Clinical
Microbiology., 38:351-353.
[22] Bonofiglio, L., Gardella, N., and Mollerach, M. (2012).
Application of Molecular Typing Methods to the Study of
Medically Relevant Gram-Positive Cocci. Gel Electrophoresis–
Advanced Techniques, 113.
[23] O'Farrell, P.Z., Goodman, H.M., and O'Farrell, P.H. (1977). High
Resolution Two-Dimensional Electrophoresis of Basic as Well as
Acidic Proteins. Cell.,12:1133-1142.
[24] Bollag, D.M., Rozycki, M.D., and Edelstein, S.J., (1996).
Protein Methods, Wiley–Liss, New York.
[25] Ciborowski, P., Silberring, J., (Eds.). (2016). Proteomic
Profiling and Analytical Chemistry: The Crossroads. Elsevier).
[26] Magdeldin, S., Enany, S., Yoshida, Y., Xu, B., Zhang, Y.,
Zureena, Z., and Yamamoto, T., (2014). Basics and Recent
Advances of Two Dimensional-Polyacrylamide Gel
Electrophoresis. Clinical proteomics, 11(1):16.
[27] Pláteník, J., (2008/2009). First Faculty of Medicine, Charles
University in Praque Electrophoresis in Biochemistry.
[28] György, M.V., (2004). Proteomics Principles and Challenges. Pure
Appl Chem., 76: 829-37.
[29] Hochstrasser, D.F., (1997). Clinical and Biomedical Applications
of Proteomics. Proteome Research: New Frontiers in Functional
Genomics., 187–220.
[30] Srinivas, P.R., Srivastava, S., Hanash, S., and Wright, G.L.,
(2001). Proteomics in Early Detection of Cancer. Clinical
Chemistry., 47:1901–1911.
[31] Şanlıoğlu, A.D., (2016).Proteomiks ve Stratejileri. Bölüm 23.
[32] Yokota, H., (2019). Applications of Proteomics in Pharmaceutical
Research and Development. Biochimica et Biophysica Acta (BBA)-
Proteins and Proteomics, 1867(1):17-21.
[33] Chiu, D.T., Lillard, S.J., Scheller, R.H., Zare, R.N.,
Rodriguez-Cruz, S.E., Williams, E.R., Orwar, O., Sandberg, M.,
Lundqvist, J.A., (1998). Probing Single Secretory Vesicles with
Capillary Electrophoresis. Science., 20;1190-3.
[34] Tristezza, M., Gerardi, C., Logrieco, A., and Grieco, F.,
(2009). An Optimized Protocol for the production of interdelta
markers in Saccharomyces Cerevisiae By Using Capillary
Electrophoresis. Journal of Microbiological Methods., 78:286–91.
[35] Chen, F.T.A., Liu, C.M., Hsieh, Y., Sternberg J., (1991).
Capillary Electrophoresis-a New Clinical Tool. Clin. Chem.,
37:14-19.
[36] Voet, D. and Voet, J.G., (1995). Biochem 2nd Edition.
[37] Petersen, J.R., Okorodudu, A.O., Mohammad, A., and Payne, D.A.,
(2003). Capillary Electrophoresis and İts Application in the
Clinical Laboratory. Clin Chim Acta., 330:1-30.

23
 Coşkun, Ö. and Öztopuz, Ö.,
Medical Sciences (NWSAMS), 1B0086, 2020; 15(1):12-25.

[38] Gauthier, M.G., (2008). Simulation of Polymer Translocation

Through Small Channels: A molecular Dynamics Study and a New
Monte Carlo Approach (Doctoral Dissertation, University of
Ottawa (Canada).
[39] Hammond, A., (2001). Microchip-based Capillary Electrophoresis:
Sequencing and Beyond. Bioresearcher Online.
[40] Wuethrich, A. and Quirino, J.P., (2019). Decade of Microchip
Electrophoresis for Clinical Diagnostics - A review of 2008-
2017. Analytica Chimica Acta., 1045:42-66.
[41] Kaneko, K., Seta, K., Soma, J., Kuwahara, T., Koizumi, M.,
Kikuchi, Y., and Yahata, K., (2014). Gamma 1-heavy Chain
Deposition Disease Accompanied by IgG kappa in Serum, Urine, and
Bone Marrow. CEN case reports, 3(1):44-48.
[42] Thadikkaran, L., Siegenthaler, M.A., Crettaz, D., Queloz, P.A.,
Schneider, P., and Tissot, J.D., (2005). Recent Advances in
Blood‐Related Proteomics. Proteomics, 5(12):3019-3034.
[43] Gupta, S., Comenzo, R.L., Hoffman, B.R., and Fleisher, M.,
(2005). National Academy of Clinical Biochemistry Guidelines for
the Use of Tumor Markers in Monoclonal Gammopathies. Section
3:K.
[44] Ercan, M., Oğuz, E.,Uysal, S., Sezer, S., Topçuoğlu, C., and
Yılmaz, F.M., (2013). Ankara Numune Eğitim ve Araştırma
Hastanesi immünfiksasyon elektroforezi verilerinin
değerlendirilmesi.Journal of Clinical and Experimental
Investigations., 4:148-152.
[45] Abraham, R.S., Barnidge, D.R., and Lanza, I.R., (2012).
Assessment of Proteins of the Immune System. In Clinical
Immunology: Principles and Practice: Fourth Edition (pp:1145-
1159.
[46] Katzmann, J.A., (2009). Screening Panels for Monoclonal
Gammopathies: Time to Change. Clin Biochem Rev., 30:105-111.
[47] Dispenzieri, A., Kyle, R., Merlin, i.G., Miguel, J.S., Ludwig,
H., and Hajek, R., (2009). International Myeloma Working Group.
International Myeloma Working Group Guidelines for Serum-Free
Light Chain Analysis in Multiple Myeloma and Related Disorders.
Leukemia., 23:215-24.
[48] Zeren, F., Genç, A., and Çürük, M.A., (2007). Preliminary Data
on Preimplantion Genetic Diagnosis for Hemoglobinopathies in
Turkey, Hemoglobin., 31:273-277.
[49] http://www.medical-labs.net/hemoglobin-electrophoresis.
[50] Michels, D.A., Hu, S., Schoenherr, R.M., Eggertson, M.J., and
Dovichi, N.J., (2002). Fully Automated Two-dimensional Capillary
Electrophoresis for High Sensitivity Protein Analysis. Mol Cell
Proteomics., 1:69-74.
[51] Kristensen, V.N., Kelefiotis, D., Kristense, T., Borresen Dale,
A.L., (2001). High Throughput Methods for Detection of Genetic
Variation, Bio Techniques., 30:318-332.
[52] Larsen, L.A., Christiansen, M., Vuust, J., and Andersen, P.S.,
(1999). High Throughput Single Strand Sonformation Polymorphism
Analysis by Automated Capillary Electrophoresis: Robust
Multiplex Analysis and Pattern Based Identification of Allelic
Variants, Human Mutation., 13:318-327.
[53] Chéry, C.C., Moens, L., Cornelis, R., and Vanhaecke, F., (2006).
Capabilities and Limitations of Gel Electrophoresis for
Elemental Speciation: A laboratory’s experience. Pure Appl.
Chem., 78:91–103.
[54] Ugaz, V.M., Lin, R., Srivastava, N., and Burke, D.T., (2003).
Burns M.A.A Versatile Microfabricated Platform for

24
 Coşkun, Ö. and Öztopuz, Ö.,
Medical Sciences (NWSAMS), 1B0086, 2020; 15(1):12-25.

Electrophoresis of Double and Single Stranded DNA.

Electrophoresis., 24:151-7.
[55] Garrels, J.L., (1999). Electrophoresis System. US Patent
5882495.
[56] Sun, W., (2010). General Procedures. In Molecular
Diagnostics (pp:49-57). Academic Press.
[57] Burgess, R.R. and Deutscher, M.P., (2009). Methods in Enzymology
Guide to Protein Purification, 2nd.
[58] Ahuja, S. and Scypinski, S., (Eds.). (2001). Handbook of Modern
Pharmaceutical Analysis (Vol:3). Academic Press.
[59] Basım, E. And Basım, H., (2001). Pulsed-field Gel
Electrophoresis (PFGE) technique and its Use in Molecular
Biology. Turkish Journal of Biology, 25(4):405-418.
[60] Pagaduan, J.V., Sahore, V., and Woolley, A.T., (2015).
Applications of Microfluidics and Microchip Electrophoresis for
Potential Clinical Biomarker Analysis. Analytical and
Bioanalytical Chemistry, 407(23):6911-6922.
[61] Ahuja, S. and Scypinski, S., (Eds.). (2001). Handbook of Modern
Pharmaceutical Analysis (Vol:3). Academic Press.

25

View publication stats