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Utility of Paper Microscope –“Foldscope” in Biomedical Research

Conference Paper · January 2020

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UTILITY OF PAPER MICROSCOPE –

“FOLDSCOPE” IN BIOMEDICAL
RESEARCH
Kelevikho Neikha, Bendangtula Walling, Abuno Thepa,
Nukshimenla Jamir, and Sarat Chandra Yenisetti*
Drosophila Neurobiology Lab, Department of Zoology, Nagaland
University (Central), Lumami 798627 Nagaland, India.
Email: yschandrays@rediffmail.com

ABSTRACT
Foldscope is a facile tool constructed using the principle of “origami”
which has a magnification of 2000x and sub micron resolution. Punched
only on a flat sheet of paper but robust enough for field study and able
to reach in resource constraint settings. Since, many individuals live in
rural or underserviced location with limited access to care, and where
infection such as malaria, Schistosomiasis and soil transmitted helminths
are rife, this novel device may be a stepping stone for future portable
diagnosis, as it is a tool with less intricacy and anyone with minimal
handling experience can readily use it. We have optimized this paper
microscope to study Drosophila sex organs, understanding of which
will help to study the process of reproduction in Drosophila model;
further I will be presenting the data relating to study of barr body in
buccal smear and basophils from the blood smear. These studies will
be of good help for biomedical researchers in their field survey/studies.
Keywords: Foldscope , Barr Body , Buccal smear, Basophil

INTRODUCTION
Foldscope is an origami-based optical microscope that can be
assembled from a flat sheet of paper and, a lens that can provide over
2000x magnification with sub micron resolution. Easy portability, flexibility,
light weight (8.8g) and minimalistic accommodation (enough to fit in a pocket
70×20×2 mm³) has made it a robust tool in resource constrained settings
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and catastrophic situation [1,2]. Traditional microscope are bulky, costly

which becomes an obstacle in resource constrained settings, frequently
results in under treatment of infectious diseases [3,4]. This expensiveness
and fragility of the microscopes inspired Dr Manu Prakash from Stanford
University, to create an affordable and sturdy microscope which will reach
the people with its frugality. The story started way back in 2011 when he
was at a field station in Thailand. He saw an expensive microscope but no
one dare to touch it as they worth five times their salary [5]. To overcome
these limitations of the conventional microscope, Dr Prakash and team
came up with the idea of making affordable and easy to use microscope, by
using folded papers and hence named “Foldscope”. They developed the
first archetype in 2014 as an easily accessible diagnostic tool in the field of
research [6]. This innovative tool is apprehending the mind of young children,
students, hobbyists, teachers and research workers [7] opening a new
window to our unknown micro world and ultimately seeks to make science
available to everyone and show “deep connection between science education
and global health”[5]. A website community called „Microcosmos is
available where foldscopist can share their work and update the latest with
other fellows.
The adroitness of this tool can have an immense impact on Medical
camp because most of the time poor road condition and electricity becomes
a hindrance in developing countries since, any kind of test needs a good
microscope along with accessories which is not easily transportable. So, in
this kind of campaign patients mostly living in developing and under developed
countries suffering from treatable neglected tropical diseases (NTD) [8]
went home getting wrong diagnosis or being ask to get blood test which
sometimes it s hard to access, in this kind of situations foldscope can be a
feasible tool to come in to play.
Foldscope has been used in various field such as study of planktons,
plant tissues, microbes, microarthropods, insect, urine crystals [9],
histopathology[2] and in diagnosis of Schistomiasis[10]. We have optimized
this paper microscope to study Drosophila sex organs, understanding of
which will help to study the process of reproduction in Drosophila model;
further we made efforts to study barr body in buccal smear and basophils
from the blood smear, knowledge of which will further the use of simple
paper microscope in biomedical research. These efforts will be discussed
in detail in the present paper.
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MATERIALS AND METHODS

Sample preparation
Processing of Drosophila reproductive organs: Using Drosophila
melanogaster as my sample study, their reproductive organ viz; ovary and
testes was dissected placing on a clean slide, added a drop of phosphate
buffer saline to avoid any tissues attached, gently transfer them onto a
cavity slides and observe under the Foldscope. The entire slides was
evaluated for a minimum of 3-5 mins and finally mounted on Samsung
Galaxy S8 + to be imaged.
Preparation of polytene chromosome: The salivary glands of the well
fed 3rd instar larvae was dissected out in physiological saline (0.7% Nacl)
and pass through 1N HCl ( fixative) for 1-2 minutes before it was transferred
to a drop of 2% Lacto aceto orcein and was left for 30-45 minutes. Then
the stained glands will be placed in a drop of 45% acetic acid on a clean
slide, a coverslip was then placed and squashed by applying pressure over
the cover slip and was observed under Foldscope and imaged on Samsung
Galaxy S8+.
Preparation of Barr body from buccal mucosal cells and basophils
from blood smear: Buccal mucosal scrapes was taken from mouth sample
and stained with alkaline methylene blue for 3 mins, rinsed the stained
sample with distilled water and observed under foldscope to be imaged.
Similarly, human blood smear was performed on a clean slide and stained
using Geimsa stain for 20 mins, washed with distilled water and air dried,
finally it was observed under the Foldscope which was mounted and imaged
on Samsung Galaxy S8 +. The following slides were observed as follows:
RESULT AND DISCUSSION
1) Demonstration of Ovary and Testes of Drosophila melanogaster

Fig. 1:(a) Ovary and (b)Testes of Drosophila melanogaster using Foldscope.

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Drosophila is an appealing model for studying adult stems cells.

Females have two ovaries and each ovary consist 16-20 tube like structures
called ovarioles, which have chains of egg chambers in increasing stages
of maturity. In ovarian follicles ecdysteroids, a steroid hormone are found
which plays a versatile role in the development of ovary [11]. The ovary of
Drosophila is also known to be one of the most powerful tools for
investigating GSC(Germ line Stem Cells) and niches. Since the ovary
consists three types of stem cells which also provides outstanding
opportunities for study of stem cells in a given tissue working together to
contribute the tissue function and maintenance[12]. The Drosophila contains
a pair of testes; each is a long blind- ended tube that is coiled around a
seminal vesicle. The testes of flies are easily distinguished from other tissues
as it is slightly yellowish in colour. At the end of spermatogenesis, the
spermatids lose their interconnections and become surrounded by individual
plasma membranes. Mature sperm are then released from the open end of
the testis into seminal vesicle, where they are stored until needed. Thus, the
testis contains a gradient of developmental stages, from stem cells in the
niche at the apical end tomature sperm at the basal end. In Drosophila
testes, ecdysone receptor (EcR with novel composition) is also involved in
male fertility, depletion of which causes cell death in male accessory glands
which fail to produce seminal fluid proteins leading to sterility of Drosophila
males [13].
2) Study of Drosophila salivary gland and polytene chromosome.

(a) (b)
Fig. 2: a) Salivary glands and b) polytene chromosomes in III instar larvae of
Drosophila melanogaster.

Drosophila salivary glands consist of two major cell types: secretory

cells and duct cells. Secretory cells are columnar epithelial cells that
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synthesize and secrete high levels of protein. Duct cells are cuboidal
epithelial cells that form the simple tubes connecting secretory cells to the
larval mouth. In the secretory cells the polytene chromosome are present
which is unit to dipterian insects. Polytene chromosomes were first
discovered by E.G. Balbiani in 1881. These are giant chromosomes which
contain thousands of DNA strands due to “endomitosis”. At interphase,
distinct thick and thin banding patterns are seen which helps to map
chromosomes, identify small chromosome mutations and in taxonomic
identification. It is also used to study function of gene and transcription
[14].
3) Study of Barr body in Human female buccal mucosal cells

Fig. 3: Demonstration of Human female buccal mucosal cells.

Human buccal mucosal cells with barr body resulting due to hetero-
chromatinization of one of the x chromosomes in human females. It was
first observed by Murray Barr in 1949 and is found only in female cells as
1X chromosome is sufficient for metabolic activity whereas absent in male
somatic cells as only 1 X is present [15]. It has been proven that buccal
mucosal scrapes forms the simplest, quick and easiest method of sex
determination when information relating to deceased is unavailable. Sex
determination becomes the first priority in the process of identification of a
person by a forensic investigator in the case of mishaps, chemical and
nuclear bomb explosions, natural disasters crime investigation and ethnic
studies.
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4) Demonstration of Human blood smear showing basophil

Fig. 4: Human blood smear showing basophil

Human blood consist of two special cells erythrocytes and

leukocytes. Human blood smear provides information on the number and
shape of cells, which can help doctors diagnose certain blood disorders or
other medical conditions. With the help of Foldscope we have observed
basophil in the above slide (Fig. 4). Basophil are rarest leukocytes less
than 1% with 9-10 µm in diameter [16]. It secretes anti-coagulant and
vasodilatory substances as histamines and serotonin which mainly function
to mediate hypersensitivity reaction.
CONCLUSION
Using Foldscope, we have demonstrated Drosophila melanogaster
sex organs, understanding of which will help to study the process of
reproduction in Drosophila model; further we have demonstrated barr
body in buccal smear of human females and basophils from the blood smear,
knowledge of which will further the use of simple paper microscope in
biomedical research. The future of Foldscope-assisted diagnostic technology
is very promising and can be a stepping stone towards treating diseases.
Along with smartphone it takes us to a different dimension where the desired
samples can be processed, clicked and shared with expertise. As it is a tool
with less intricacy; little adjustment is needed on spherical and chromatic
aberration [17] and anyone with minimal handling experience can readily
use it in every nook and corner of the world.
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ACKNOWLEDGEMENTS
This work is supported by the DBT (Department of Biotehnology, India)
grant No. BT/IN/Indo-US/Foldscope/39/2015, dated 20-3-2018 awarded
to corresponding author Dr. Sarat C. Yenisetti, Department of Zoology,
Nagaland University, Lumami.
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