A prototype miniature medical device, unique
in nature, because its location can be precisely identified within the body (something
that proved challenging before) has been developed by researchers at Caltech
- The function of miniature wireless medical devices
such as biosensors and drug-delivery systems depends critically on their
location inside the body.
- Currently, localizing and communicating with such
devices using existing electromagnetic, acoustic and imaging-based methods
is limited by physical tissue properties or performance of imaging
- ATOMS is a new technology involving a silicon
integrated circuit that uses the principles of nuclear magnetic resonance
to accurately detect the location of microdevices.
technology could ultimately be used in "smart pills" to diagnose and
"The dream is that we will have
microscale devices that are roaming our bodies and either diagnosing problems
or fixing things," says Azita Emami, the Andrew and Peggy Cherng Professor
of Electrical Engineering and Medical Engineering and Heritage Medical Research
Institute Investigator, who co-led the research along with Assistant Professor
of Chemical Engineering and Heritage Medical Research Institute Investigator
Mikhail Shapiro. "Before now, one of the challenges was that it was hard
to tell where they are in the body."
‘Combination of the ATOMS technology with microscale biological sensing to detect precise location of microdevices, will help in varied biomedical applications like monitoring and localizing biologically relevant biomarkers, targeted release of therapeutic agents and tissue imaging for disease diagnosis.’
The research appears in the September issue of
the journal Nature Biomedical Engineering
. The lead author is
Manuel Monge, who was a doctoral student in Emami's lab and a Rosen
Bioengineering Center Scholar at Caltech.
ATOMS - addressable transmitters operated as
The miniature medical devices are silicon-chip
devices called addressable transmitters operated as magnetic spins (ATOMS) that
use principles of magnetic resonance imaging (MRI), in which the location
of atoms in a patient's body is determined using magnetic fields.
While the microdevices would also be located
in the body using magnetic fields, the chips contain a set of integrated
sensors, resonators, and wireless transmission technology that would allow them
to mimic the magnetic resonance properties of atoms instead of relying on the
"A key principle of MRI is that a
magnetic field gradient causes atoms at two different locations to resonate at
two different frequencies, making it easy to tell where they are," says
Shapiro. "We wanted to embody this elegant principle in a compact
integrated circuit. The ATOMS devices also resonate at different frequencies
depending on where they are in a magnetic field."
The invention of ATOMS was serendipitous and
happened one day when Shapiro and Emami were discussing their respective
fields. Shapiro engineers cells for MRI and other medical imaging techniques
and Emami creates microchips for medical sensing and performing actions in the
body; they chanced upon the idea that combining MRI technology in creating
microdevices could potentially resolve the long-standing challenge of locating
microdevices in the body.
"This chip is totally unique: there are
no other chips that operate on these principles," says Monge, who was
enlisted to help realize the idea in the form of a silicon chip.
"Integrating all of the components together in a very small device while
keeping the power low was a big task."
The device consists of a magnetic field
sensor,, a wireless powering device, and a circuit that adjusts its radio
frequency signal based on the magnetic field strength to wirelessly relay the
The operation of the device consists of three phases:
magnetic phase which senses, processes and stores the applied magnetic
field at each of their locations.
excitation phase that starts when the radiofrequency or RF pulse is
applied. At this point, the frequency of the RF pulse f0 is acquired, and the devices
start oscillating at the same frequency.
transmission phase during which each device emits a signal with a
shifted frequency proportional to the measured magnetic field.
The final prototype chip was tested and proven
in mice and had the advantages of having
- A very small surface area of 1.4 square millimeters
- Low power consumption
The above two things had to be balanced
correctly so that the chip's location can be determined precisely.
"You could have dozens of microscale
devices traveling around the body taking measurements or intervening in
disease. These devices can all be identical, but the ATOMS devices would allow
you to know where they all are and talk to all of them at once," says
In ATOMS, the features that are intrinsically
found in atoms in the human body had to be recreated.
Although the research is still at a
preliminary stage, miniature robotic devices canto
- Monitor a patient's gastrointestinal tract, blood,
- Measure factors such as pH, temperature, pressure,
sugar concentrations - that indicate the health of a patient
- Relay health information to doctors
- Be instructed to release drugs
Plans for ATOMS
Now that the chip can relay its location in
the body, the next research addition to its function is make it sense body states.
"We want to build a device that can go
through the gastrointestinal tract and not only tell us where it is but
communicate information about the various parts of the body and how they are
- Manuel Monge, Audrey Lee-Gosselin, Mikhail G. Shapiro & Azita Emami. Localization of microscale devices in vivo using addressable transmitters operated as magnetic spins. Nature Biomedical Engineering 1, 736-744 (2017) doi:10.1038/s41551-017-0129-2