Robotic sperm (also called spermbots) are biohybrid
microrobots consisting of
sperm cells
A spermatozoon (; also spelled spermatozoön; ; ) is a motile sperm cell, or moving form of the haploid cell that is the male gamete. A spermatozoon joins an ovum to form a zygote. (A zygote is a single cell, with a complete set of chromosome ...
and artificial microstructures.
Currently there are two types of spermbots. The first type, the tubular spermbot, consists of a single sperm cell that is captured inside a microtube. Single bull sperm cells enter these microtubes and become trapped inside. The tail of the sperm is the driving force for the microtube.
The second type, the helical spermbot, is a small helix structure which captures and transports single immotile sperm cells. In this case, a rotating
magnetic field
A magnetic field is a vector field that describes the magnetic influence on moving electric charges, electric currents, and magnetic materials. A moving charge in a magnetic field experiences a force perpendicular to its own velocity and t ...
drives the helix in a screw-like motion. Both kinds of spermbots can be guided by weak magnetic fields.
These two spermbot designs are hybrid microdevices, they consist of a living cell combined with synthetic attachments. Other approaches exist to create purely synthetic microdevices inspired by the swimming of natural sperm cells, i.e. with a
biomimetic
Biomimetics or biomimicry is the emulation of the models, systems, and elements of nature for the purpose of solving complex human problems. The terms "biomimetics" and "biomimicry" are derived from grc, βίος (''bios''), life, and μίμησ ...
design, for example so-called Magnetosperm which are made of a flexible
polymer
A polymer (; Greek ''poly-'', "many" + '' -mer'', "part")
is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic and ...
ic structure coated with a magnetic layer and can be actuated by a magnetic field.
Design
''Tubular spermbots''
Initially, the microtubes for the tubular spermbots were made using roll-up nanotechnology on
photoresist
A photoresist (also known simply as a resist) is a light-sensitive material used in several processes, such as photolithography and photoengraving, to form a patterned coating on a surface. This process is crucial in the electronic industry.
...
. In this process, thin films of
titanium
Titanium is a chemical element with the Symbol (chemistry), symbol Ti and atomic number 22. Found in nature only as an oxide, it can be reduced to produce a lustrous transition metal with a silver color, low density, and high strength, resista ...
and
iron
Iron () is a chemical element with symbol Fe (from la, ferrum) and atomic number 26. It is a metal that belongs to the first transition series and group 8 of the periodic table. It is, by mass, the most common element on Earth, right in ...
were deposited onto a sacrificial layer. When the sacrificial layer was removed, the thin films rolled into 50 μm long microtubes with a diameter of 5 - 8 μm. Later on, the microtubes were made from a
temperature-responsive polymer
Temperature-responsive polymers or thermoresponsive polymers are polymers that exhibit drastic and discontinuous changes in their physical properties with temperature. The term is commonly used when the property concerned is solubility in a giv ...
to enable the controlled release of the sperm cells upon a small temperature change of a few degrees.
Tubular spermbots are assembled by adding a large amount of the microtubes to a diluted sperm sample under the microscope. The sperm cells randomly enter the microtubes and become trapped in their slightly conical cavity. In order to increase the coupling efficiency between sperm cells and microtubes, the microtubes have been functionalized with proteins or sperm
chemoattractant
Chemotaxis (from '' chemo-'' + '' taxis'') is the movement of an organism or entity in response to a chemical stimulus. Somatic cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemi ...
. This has been done using
thiol
In organic chemistry, a thiol (; ), or thiol derivative, is any organosulfur compound of the form , where R represents an alkyl or other organic substituent. The functional group itself is referred to as either a thiol group or a sulfhydryl gro ...
chemistry once the tubes are rolled-up or by transferring the
molecule
A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bio ...
s with an
elastomer
An elastomer is a polymer with viscoelasticity (i.e. both viscosity and elasticity) and with weak intermolecular forces, generally low Young's modulus and high failure strain compared with other materials. The term, a portmanteau of ''elastic ...
stamp onto the material before rolling the tubes.
''Helical spermbots''
Helical spermbots are assembled by driving a magnetic microhelix over an individual sperm cell, thereby confining its tail inside the helix
lumen and pushing the head of the sperm forward. The sperm cell is loosely coupled to the helix and can be released by reversing the rotation of the helix, letting it withdraw from the head and free the confined tail in the process. Such microhelices were fabricated by
direct laser lithography
Multiphoton lithography (also known as direct laser lithography or direct laser writing) of polymer templates has been known for years by the photonic crystal community. Similar to standard photolithography techniques, structuring is accomplished ...
and coated with
nickel
Nickel is a chemical element with symbol Ni and atomic number 28. It is a silvery-white lustrous metal with a slight golden tinge. Nickel is a hard and ductile transition metal. Pure nickel is chemically reactive but large pieces are slow ...
or iron for magnetization.
Navigation
Robotic sperm can be navigated by weak external magnetic fields of a few
mT. These fields can be generated by
permanent magnets
A magnet is a material or object that produces a magnetic field. This magnetic field is invisible but is responsible for the most notable property of a magnet: a force that pulls on other ferromagnetic materials, such as iron, steel, nickel ...
or by a setup of
electromagnet
An electromagnet is a type of magnet in which the magnetic field is produced by an electric current. Electromagnets usually consist of wire wound into a coil. A current through the wire creates a magnetic field which is concentrated in the ...
s. The applied magnetic field can be a homogeneous, rotating, or
gradient
In vector calculus, the gradient of a scalar-valued differentiable function of several variables is the vector field (or vector-valued function) \nabla f whose value at a point p is the "direction and rate of fastest increase". If the gr ...
field. Tubular and helical spermbots can also be navigated in a
closed-loop control
Control theory is a field of mathematics that deals with the control of dynamical systems in engineered processes and machines. The objective is to develop a model or algorithm governing the application of system inputs to drive the system to a ...
scheme with an
electromagnetic coil
An electromagnetic coil is an electrical conductor such as a wire in the shape of a coil (spiral or helix). Electromagnetic coils are used in electrical engineering, in applications where electric currents interact with magnetic fields, in de ...
setup.
Applications
Spermbots hold promise for potential application in single cell manipulation and
assisted reproduction
Assisted reproductive technology (ART) includes medical procedures used primarily to address infertility. This subject involves procedures such as in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), cryopreservation of gametes o ...
, but also for
targeted drug delivery Targeted drug delivery, sometimes called smart drug delivery, is a method of delivering medication to a patient in a manner that increases the concentration of the medication in some parts of the body relative to others. This means of delivery is la ...
. A recent study shows that modified tubular spermbots can be used for delivery of
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bl ...
drugs.
In this case, the sperm cell is loaded with
doxorubicin
Doxorubicin, sold under the brand name Adriamycin among others, is a chemotherapy medication used to treat cancer. This includes breast cancer, bladder cancer, Kaposi's sarcoma, lymphoma, and acute lymphocytic leukemia. It is often used tog ...
. The artificial microstructure fabricated by
two-photon nanolithography captures the drug-loaded sperm cell. The sperm cell is the actuation source for the magnetic microstructure and can propel it to
cancer spheroids. At this location, the drug-loaded sperm is released by a spring mechanism and the sperm cell delivers the drug to the cancer cells.
Perspectives
Robotic sperms as
microswimmer
A microswimmer is a microscopic object with the ability to move in a fluid environment. Natural microswimmers are found everywhere in the natural world as biological microorganisms, such as bacteria, archaea, protists, sperm and microanimals. ...
s are interesting for diverse biomedical applications, specifically for new assisted fertilization techniques and for the targeted delivery of therapeutic cargo. These microswimmers are meant to operate in ''
in vivo
Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...
'' environments, a feature that may revolutionize assisted reproduction technologies and
nanomedicine
Nanomedicine is the medical application of nanotechnology. Nanomedicine ranges from the medical applications of nanomaterials and biological devices, to nanoelectronic biosensors, and even possible future applications of molecular nanotec ...
in the future.
New designs are emerging and plenty of applications can be derived from the here reported concept.
References
{{reflist
Medical robotics
Nanotechnology