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Design of Nanorobots for Exposing Cancer Cells

Article in Nanotechnology · April 2019

DOI: 10.1088/1361-6528/ab1770

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 Design of Nano-Robots for Exposing Cancer Cells
Shlomi Dolev1, Michael Rosenblit2, and Ram Prasadh Narayanan1
1
Department of Computer Science, Ben-Gurion University of the Negev, Israel. Email: {dolev, narayan}@cs.bgu.ac.il
2
Ilse Katz Institute of Nano-Scale Science and Technology, Ben-Gurion University of the Negev, Israel.

Abstract—A proof-of-concept design of a nano-robot which harvester electrodes and cylindrical capacitor, (ii) Detector
can navigate, detect cancer cells in blood and actuate the and (iii) Actuator. We believe this facile theory of inorganic
release of drugs is discussed. The nano-robot was designed nano-robot platform design can help to bridge the gap between
with blood energy harvesting capability and accumulation of existing research on bio-nano-sensing in combination with
electricity in a capacitor, which forms the main body of the advanced nano transistor technology towards cancer
nano-robot. Glucose hunger-based cancer detectors treatment. A collective system of electrical manipulation, bio-
immobilized on the nano-robot, reduces its electrical detection and NEM actuation can visualize the
resistance, when attached to a cancer cell. This mechanism, programmability in the nano matters.
in-turn, allows electric current to activate a nano-electrical- II. DESIGN OF NANO-ROBOT STRUCTURE
mechanical (NEM) relay (mechanical transistor) to break the
ceiling, exposing a drug identified by the immune system for A. Energy harvester and Metal-Insulator-Metal (M-I-M)
cell elimination. This concept is in line with the effort to cylindrical nano-capacitor
design an autonomous computational nano-robot for in-vivo A nano-robot can be termed autonomous if there is no
medical diagnosis and treatment. A collective system of dependency on external sources for its operation. The first step
electrical manipulation, bio-detection and NEM actuation can to visualizing an autonomous nano-robot is to provide a self-
visualize the programmability in the nano matters. The sustained energy source to it. We show this feasibility by
concept can also be considered as a step to bridge the gap harvesting energy from the blood. In references [3 − 5],
between theoretical swarming/navigation techniques and a inorganic glucose energy harvesters were fabricated and
computational hardware for plausible implementation of the analyzed for their efficiency. Certain inorganic materials, like
theory. platinum, graphene etc., are used as electrodes due to their
bio-compatibility and tested usage scenarios. An open circuit
I. INTRODUCTION voltage, of 192−860 mV, was reported from glucose fuel
cells. Capacitance estimation of a cylindrical capacitor, based
In general, programmable matter is any matter that can on properties of blood, particularly, its glucose concentration,
change its physical properties (like shape, density, moduli, is detailed below.
conductivity, optical properties, etc.) based on user input or
autonomous sensing. Advances in electronic fabrication At injection, the nano-robots are under constant influence
satisfies the necessity of resource adequacy in nano of the blood. The velocity of blood flow ranges from (0.3 −
computational systems. Moreover, the implementation 40) cm/sec and the glucose concentration in blood is (3.9 −
feasibility of particle systems make it possible to incorporate 6.4) mM/L. With an estimated harvester total surface area of
nano-computational systems into materials used in paint (2.041 x 10 ) cm2 (Fig.1) and with the displacement of
coating, structural integrity, vibration sensors etc. With (0.3 − 40) cm, the volume of blood interacting with the nano-
personalized medical care and targeted drug delivery practices robot per second is estimated to be (6.123 − 816.4) x 10
on the rise, the inclusion of nano-machines for medical L/Sec. On average, if 5.5 mM/L is the concentration of
diagnosis and treatment is a growing research field. glucose, the number of moles of glucose interacting with the
Nano-robotics is a rapidly growing interdisciplinary field nano-robot and the number of electrons in the interacting
addressing the assembly and utilization of molecular devices glucose concentration is calculated to be (33.67 − 4490.2) x
based on nano-scale principles [1]. In our previous work [2], 10 mM/Sec and (40.4 − 5408.8) x 10 Electrons/Sec,
we presented a swarming algorithm for in-vivo nano-robots, respectively. This gives the source current of the harvester to
inspired by caterpillar swarm in nature, wherein the nano- be (64.64 − 8654) nA. The capacitance is calculated to be
robots were considered as large quantities of programmable (4.702 x 10 ) F.
matter. We suggested instructing the computational particles
to create layered and connected structures for the benefit of To compliment the calculations of the capacitance, we
speed and energy preservation. We put forward a proposition simulated a 3-D model of a concentric cylindrical Metal-
that the theoretical concept needs to be supported by hardware Insulator-Metal (M-I-M) encapsulated capacitor (Fig.1) using
feasibility for a plausible implementation of a computational COMSOL Multiphysics (License #17076110). The capacitor
nano-robot. Through this work, we have attempted to design is charged to the open circuit voltage V . The height and
autonomous nano-robots which can harvest energy from the diameter of the structure was fixed at 100 nm and 90 nm,
glucose in the blood and activate a response, based on bio- respectively. A 10 nm thick outer electrode layer is assumed
detection. We will present below the design of the nano-robot for the energy harvester. Each metal cylinder is 10 nm in
structure with three modules, (i) External coated energy thickness. Four metal cylinders are arranged concentrically

978-1-5386-5336-4/18/$31.00 ©2018 IEEE

(inside each other) with 4 nm thick dielectric layers separating glycolysis) [7]. In our design, we intend to use metallic
them. The alternate metal cylinders are imagined extending carbon-nanotubes (CNTs), immobilized with variants of
outside along the vertical axis at the extremes to differentiate glucose that can attach themselves to the cancer cells by
positive and negative cylinders connected to respective detecting the glucose hunger in them. In a sense, the nano-
electrodes of the harvester. This design was chosen to increase robots use glucose hunger and concentration change for
the surface area of the capacitor, eventually improving the navigation and detection. Fig. 2 shows a schematic of an
capacitance. attached CNT to a cancer cell.

Fig 2: Schematic (not in scale) of a cancer cell attached to a

drug immobilized CNT platform
Enzyme-coated SWCNTs, referred here [8], showed strong
pH dependence, wherein the conductance of glucose oxidase
(GOx) immobilized CNTs increased by over 10% when
Fig 1: Structure of the concentric cylindrical capacitor glucose molecules were detected, suggesting their use for
glucose hunger and bio-detection. The conductance of the
The structure was designed with platinum metal electrodes immobilized glucose hunger detector before and after
and quartz dielectric ( ε = 4.7 and σ = 10 S/m). detection is given as:
Appropriate boundary conditions were applied at the interface
of air/dielectric in the alternate discs. The capacitance of the Before glucose hunger detection: ~2.4 μS
device was computed to be 4.824 x 10 F. The calculated 1
and simulated capacitance were nearly equal. The simulated = = 0.42MΩ
structure is precisely maintained within a 100 nm dimension 2.4
to (i) Qualify the structure as a nano-robot, (ii) To allow the After glucose hunger detection: ~2.7 μS
nano-robot to immobilize itself on the cell surface and act as a 1
parasite. The provided energy harvesting capability will = = 0.37 MΩ
enhance the nano-robot to power, in particular, the detector 2.7
that will be used for actuation. We tune up the design of the detector so that the change in
conductance, before and after immobilization, can be
B. Bio-Detector attributed to the capacitance change of the CNT. We are aware
A collective system of electrical manipulation, bio- of the quantum effects in CNT devices which would be
detection and NEM actuation can visualize the considered when the design is elaborated.
programmability in the nano matters. The second part of our
proof-of-concept is to show the bio-detection mechanism of C. Actuator
cancer cells and to provide an electrical output for logical Until this stage, the concept is extended to the point where
decisioning. Detection of tumor cells, in-vivo, also means the nano-robots are autonomous in terms of their power and
active navigation of the nano-robots using chemical navigation, have the capability of bio-detection and
pheromones, acoustic vibrations, photo/fluorophores etc., for computationally equipped to handle a bit change of
binding to tumor tissues. We propose using the glucose hunger information. We will discuss further, the possibility of a Nano-
Elecro-Mechanical (NEM) switch which can get triggered by
of cancer cells to yield the navigation of nano-robots in blood
the conductance change of immobilized CNT bio-detector.
[6]. Assuming that our nano-robots can swim randomly in
This will ensure that programmable matters will respond
blood, get attracted to glucose hunger locations, harvest and appropriately depending on the decided logical operation.
store energy from the blood glucose, the next step would be to Miniature mechanical switches suitable for applications,
utilize stored charges for a logical decision making. The which require less than 100 mV for operation, were
black-box between harvested energy and decisioning is the demonstrated here [9, 10].
mechanism of bio-detection. A chemical detection of a cancer
cell should induce a change in the charge flow between the A NEM actuator switch was demonstrated to operate with
electrodes. This hysteresis in charge flow rate can be a minimum switching voltage of 80 mV [9]. We have already
considered as an electrical normalized low and high. shown in a previous section that a cylindrical capacitor can
harvest sufficient charges to provide an operable voltage of
The warburg effect states that cancer cells effectively 192 − 860 mV. Here, we show that a mechanical chamber
consume 28 % more glucose than normal cells (anaerobic can be designed to lock a necessary drug or a combination of
drugs that can be unlocked when increase in electrical power
flow (due to bio-detection), provides adequate electrostatic
force to break the ceiling of the chamber, eventually exposing
the drug to the environment. This setup can be synonymous to
color change or fluorescent marking of a programmable
matter. In this regard, we calculated and simulated a NEM
actuator which can be broken. Within a unit time constant
τ = RC, where R is the resistance and C is the capacitance of
the energy harvester, the operating voltage, supplied from the
energy harvester, is expected to drop from 200 mV to 70 mV.
This discharge (until ~1τ ) can be utilized to provide an Fig 4: Sketch of the NEM Actuator as a parallel plate
operable current and voltage for the NEM device actuation. capacitor with sheet resistance
The mechanical break exposes a detectable drug that triggers
the immune system to recognize the attached nano-robot and PMMA polymer material was constructed as the NEM
the cancer cell. Hence, the electrostatic force acting on the chamber electrode. A non-solid air vacuum was filled as the
parallel plates due to change in dielectric thickness is given by dielectric. The chamber electrode was fixed at its
circumference and simulated. The upper chamber is supported
= = along its outer surface from below. The chamber can be
considered as a ceiling, supported along all sides. This design
where, and are the breakdown voltage and force of the makes sure that the electrostatic force acts uniformly and
NEM chamber with the glued drug inside it, is the area of perpendicular to the chamber surface. Thus, the stress on the
the ceiling, and d is the distance between the plates. Fig. 3 overall structure is distributed uniformly. The electrostatic
shows the circuit schematic and its equivalent sketch of the force on the chamber electrode was found to be 1.476 nN.
chamber. In a regular 3-dimensional structure, the sheet resistance is
given by
ℎ
=

where, ρ is the resistivity, given as ρ = , σ , being the

conductivity of the material, is the sheet resistance, h, W
and t are the height, width and thickness of the sheet
respectively. COMSOL was used to check the correctness of
Fig 3: Sketch showing the resistances and the chamber these calculations. A similar structure was built with the
The resistances R and R tune the breakdown voltage V , inclusion of the electric currents (ec) module. In a linear case,
such that the NEM chamber collapses. With an increase in V the leakage current across the sheet and a potential difference
(due to the resistance change after detection), is increased in the sheet are proportional; the sheet resistance being the
to reach , the force required to trigger a permanent proportionality constant. The thickness was computed to be
breakage. Before the detection, there is a leakage of current 1.5 nm, same as the value calculated manually. The selection
from the energy harvester to the actuator. The discharge also of NEM actuator material is based on certain parameters like
happens through the resistor R (Fig. 3c). Thus, the value of true stress, tensile strength, physical dimensions of the
R2 must be maintained, such that, the discharge is lesser than actuator etc. The true stress (σ ) of the chamber electrode can
the charging rate and at the same time, the charge-discharge vary between ≤ ≤ meaning, that can vary
rate of the actuator capacitor is higher and lesser than the between ≤ ≤ . The electrostatic forces
charging time of the energy harvester before and after and are the minimum and maximum thresholds of the
detection, respectively. force respectively, where + Δ is the ultimate
An increase in input voltage, V due to detection, will electrostatic force where a breakage is certain to occur. Thus,
result in the breakage of NEM box (when V reaches V ), the electrostatic force acting on the chamber surface is
thus exposing the glued drug. The drug is glued to keep the presumably smaller than , before detection, and higher
target associated with the cancer cell rather than being than , after detection, i.e.,
distributed in the blood. The simulated structure of the
actuator is shown in Fig. 4. The top and bottom metal layers Before Detection: = , where, <
are of dimensions (80 x 50 x 2) with a dielectric thickness of (Stable)
3 nm.
After Detection: = , where, ≥
(Breaking)

The electrostatic force, due to the applied voltage is equal to

the applied force (due to a load) on the chamber electrode.
Therefore, the condition for after detection can be rewritten as
 1 estimated ~1 nm width [15]. These dimensions fit the inner
× =
2 space of the activation chamber. FlaB protein is considered a
where, Ac is the area of the actuator ceiling, given by 2(l + foreign particle by all vertebrates, including human beings,
w) × , where l and w are the length and width of the thus provoking the CTLs to unleash an attack on the flagellin
chamber electrode, is the thickness of the surface connected absorbed cell. It is possible to immobilize the desired protein
to the lower electrode and is the area that suffers from the inside the chamber of the nano-robots, which, on detection,
shear force. Once the applied voltage reaches V , the relay breaks to double mask the cancer cells as viral/bacteria
becomes unstable, thus resulting in a permanent breakage. The infected cells. Though the idea of nano-robots passively
current I through the actuator and the current I l depleted treating cancer cells is still in a conceptual stage, a non-fatal
through , are given by antigen on the nano-robot exposing a cancer cell, can increase
the efficiency of immunotherapy.
= ; = ; = ×
III. CONCLUSION
where, is the supply voltage to the actuator, is the
breakdown voltage, is the detector CNT and is the sheet A facile approach of an energy harvester, glucose hunger
resistance. The current I is given by detector for cancer cells and actuator for drug exposure design
is discussed. A collective system of electrical manipulation,
= = 0.476 μ (Before detection) bio-detection and NEM actuation to visualize the
.
programmability in nano-robots are presented. The
= = 0.54 μ (~11% increase after detection) calculations and simulation results provide a proof-of-concept
.
towards a plausible implementation of an autonomous
200
= = 0.25 μ computational nano-robot with bio-detection, logical
0.4 + 0.4 decisioning and actuation for drug exposure. To the best of
We verified our claims by simulating the model circuit. our knowledge, this work is the first of its kind that presents
The model was built according to the node names prescribed an overall picture towards an autonomous computational
in Fig. 5. The leakage current was calculated/simulated to be nano-robot for cancer diagnosis and treatment.
lesser than (half) the actuator current, which in turn implies
doubling the time that is needed to charge the actuator, i.e, ACKNOWLEDGMENTS
doubling the time, before and after detection.
We thank the Lynne and William Frankel Center for
Computer Science, the Rita Altura Trust Chair in Computer
Science, the Kreitman School of Advanced Graduate Studies,
Ben-Gurion University of the Negev for their support to this
work. This research was also supported by a grant from the
Ministry of Science & Technology, Israel & the Japan Science
and Technology Agency (JST), Japan. We also thank Prof.
Zeev Zalevsky from Bar-Ilan University for his useful
comments and assistance.
Fig 5: Circuit schematic for a NEM Actuator REFERENCES
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