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Boisen received her Master’s degree in Physics and Mathematics from Roskilde University. She worked as a highschool teacher for almost a year before starting an industrial PhD with the company “Danish Micro Engineering”, which she finished in 1997. She was hired as a postdoc at the Technical University of Denmark (DTU) and was awarded a research grant to begin her research group: the DNRF Center for Intelligent Drug Delivery and Sensing Using Microcontainers and Nanomechanics (IDUN), where she is currently the Head of Sections. She became an Associate Professor at DTU in 1999 and a Professor in 2005. IDUN has several spinout companies including Cantion, Silmeco, and BluSense Diagnostics.
Boisen was awarded the largest research prize in Denmark: the Villum Kann Rasmussen award. In 2012 she was awarded the EliteForsk Award from the Danish Ministry of Research, Innovation and Higher Education. In 2013 she received the Sapere Aude Top Researcher Award from the Danish Council for Independent Research.
Boisen’s work in micro and nanotechnology is innovating the way drugs are delivered and characterized. Her two research areas (biochemical sensing and drug delivery via microdevices) work synergistically and have the potential to both better monitor the treatment of diseases such as cancer and safely deliver the treatments.
Tests for dengue can often take several days to receive results and the cost can prevent patients from seeking a diagnosis, which is critical to reduce the spread of the virus. Boisen’s lab-on-a-disk research is an example of remarkable engineering of a bottom-up design, which has led to increased access to accurate and affordable testing done by the BluBox machine from BluSense Diagnostics.
https://dg.dk/en/centers/center-for-intelligent-drug-delivery-og-nanomekaniske-sensorer-idun/
https://www.healthtech.dtu.dk/english/research/research-sections/section-idun
https://www.su.org/experts/anja-boisen
https://kvinderifysik.dk/2020/12/06/professor-anja-boisen-is-awarded-the-order-of-the-dannebrog/
https://dg.dk/en/dtu-writes-article-about-the-career-of-head-of-center-anja-boisen/
Slide-specific speaker notes:
Science details:
Centrifugation is a mechanical process that utilizes the centrifugal force to separate particles in a solution based on their physical properties, the viscosity of the medium, and the rotor speed. The solution (a liquid suspension of particles in a liquid medium) is placed in a centrifuge tube which is then placed in a rotor and spun at a particular speed. Centrifugation speeds along the process of gravity separating the larger/denser particles via sedimentation, wherein the particles are drawn to the bottom of the container along the axis of the centrifuge. As the suspension is rotated at a certain angular velocity or revolutions per minute (RPM), the centrifugal force acts on the particles and allows them to travel away from the rotation axis in the radial direction. The sedimentation rate of a particle is proportional to its molecular weight and the difference between the particle’s density and the density of the solution.
The general formula for the RPM of a centrifuge is a function of the respective force of the centrifuge (g) and the radius from the center of the rotor to a point in the suspension (r).
The magnitude of a centrifugal force F on an object of mass m is a function of m, the angular velocity of the rotating object (ω), and the distance from the origin of the rotating object’s reference frame to the object of mass m (r).
Citations and resources:
https://www.fishersci.se/se/en/scientific-products/centrifuge-guide/centrifugation-theory.html
https://en.wikipedia.org/wiki/Centrifugation
https://en.wikipedia.org/wiki/Centrifugal_force
https://en.wikipedia.org/wiki/Centrifugal_force
Figures:
Top: Schematic of a centrifuge (left). An armored casing houses the centrifuge tube which contains a mixture of supernatant (blue liquid) and pellets (dark blue dots). The armored casing is attached to a rapidly rotating rotor. The solution is separated after centrifugation, with the denser components collected at the bottom of the centrifuge tube (right). https://microbiologynote.com/centrifugation/
Bottom: Diagram of the centrifugal force (red arrow) pointing radially outward from the axis of an object rotating with angular speed ω (black arrow). The velocity (dark blue arrow) of the object is perpendicular to centrifugal force acting on it. Adapted from https://microbiologynote.com/centrifugation/
Science details:
Boisen is the Head of Sections at IDUN: a Copengagen-based research group working on micro and nano sensor development and microdevices for drug delivery. The IDUN sensor projects focus on developing and analyzing new nanomechanical sensor systems to study the behavior and physical properties of molecules and cells. They research and develop sensing using centrifugal microfluidics on a lab-on-a-disk device.
Boisen co-founded several spin-out companies from her research group, including BluSense Diagnostics. Her research led the company to develop a portable machine that is able to diagnose dengue and COVID-19 (and they intend to expand to other infectious diseases) from a drop of blood using technology based on a Blu-ray player. The test is run by taking a blood sample and mixing it with magnetic nanoparticles, then loading it onto the BluSense machine which uses a small turntable to centrifuge the sample for several minutes. The turntable is coated with biomolecules that will bind to biomarker particles if they are present in the sample, causing them to collect together. The results are not visible to the naked eye, but can be seen using a blue laser (the same as the laser of a Blu-ray player).
Because they have repurposed existing technology, it only took four years from building the prototype to selling the first machines in Thailand. Medical facilities can run diagnostics using the machines for a cost of $20 per patient - significantly cheaper and more accessible than private testing.
Citations and resources:
https://www.su.org/experts/anja-boisen
https://idun.dtu.dk/Research/Sensor
https://www.healthtech.dtu.dk/english/research/research-sections/section-idun
https://www.engadget.com/2017-05-30-zika-test-machine-needs-just-a-drop-of-blood.html
https://www.youtube.com/watch?v=itn1CpCA8z0
https://www.blusense-diagnostics.com/products/#blubox
Figures:
Left: Photo of a spinning disk used for centrifugal microfluidics. https://idun.dtu.dk/Research/Sensor
Right: Photo of BluSense’s BluBox machine used to diagnose infectious diseases. A health professional is shown inserting a disk into the machine. https://good-design.org/projects/blubox/
Science details:
Boisen is the Head of Sections at IDUN: a Copenhagen-based research group working on micro and nano sensor development and microdevices for drug delivery. The IDUN drug projects focus on investigating the use of micrometer sized containers as a way of delivering drugs (such as insulin, vaccines, and antibiotics) orally. They use existing drug formulations but aim to increase the oral bioavailability of drugs by stabilizing them and retaining as much drug as possible through the passage from the mouth to the small intestine where the drugs are absorbed. Their goal is to limit the discomfort, inconvenience, and safety issues posed by injections.
The microcontainers are fabricated by nano and micro fabrication techniques, then they are filled with medicine in a way that IDUN compares to making a Toffifee chocolate. The empty polymer container is filled with medine then a polymer lid is attached to close the container (like filling a caramel shell with nougat then closing it with a chocolate lid). The lid should be pH sensitive so that the medicine is released unidirectionally into the cell wall of the small intestine, increasing the chances of absorbing the drug into the bloodstream.
The entire process is undergoing research: fabricating the polymer shell involves photolithography, embossing, and 3D printing, and the morphology of the shells is being investigated to determine which sizes and shapes best protect the drugs during their journey through the GI tract. Filling the polymer shells requires researching formulations of medicine and polymer, and the filling technique involves CO₂ impregnation and punching. It is also essential to choose the right material for the microcontainer lids to be sure of a controlled release into the intestinal wall.
Citations and resources:
https://idun.dtu.dk/Research/Drug
https://www.su.org/experts/anja-boisen
https://www.healthtech.dtu.dk/english/research/research-sections/section-idun
Figures:
Top: Photo of a gel capsule containing microcontainers. Each microcontainer is approximately the size of a grain of salt. https://idun.dtu.dk/
Bottom: Diagram of the microcontainer concept. The process of filling the microcontainer is compared to making a Toffifee chocolate: the microcontainer (analogous to a Toffifee caramel shell), which is 70-300 μm in height and 300 μm wide, is filled with medicine (analogous to nougat and nut), then closed with a lid (analogous to a chocolate lid) which dissolves and releases the medicine in one direction. https://www.youtube.com/watch?v=VLNGCW6ea6M
Science details:
Boisen is the Head of Sections at IDUN: a Copenhagen-based research group working on micro and nano sensor development and microdevices for drug delivery. The IDUN drug projects focus on investigating the use of micrometer sized containers as a way of delivering drugs (such as insulin, vaccines, and antibiotics) orally. They use existing drug formulations but aim to increase the oral bioavailability of drugs by stabilizing them and retaining as much drug as possible through the passage from the mouth to the small intestine where the drugs are absorbed. Their goal is to limit the discomfort, inconvenience, and safety issues posed by injections.
The oral delivery of drugs using microcontainers is tested first in vitro (studies performed outside a living organism) then in vivo (animal studies using mice and rats). An in vitro study would be measuring how much drug is released from the microcontainers in a gastric medium (pH of 1.6) versus an intestinal medium (pH of 6.5). In vivo experiments involve measuring the concentration of the drug in the animal’s bloodstream at different times. The results show increased bioavailability for a longer period of time when compared to the control (delivery without microcontainers). IDUN faces challenges moving forward because the human GI tract is long so the microdevices need to stay intact for longer while also using biodegradable materials so that plastics do not accumulate in the body.
Citations and resources:
https://www.su.org/experts/anja-boisen
https://www.healthtech.dtu.dk/english/research/research-sections/section-idun
https://idun.dtu.dk/Research/Drug
https://www.youtube.com/watch?v=P0Y9sqXAHo0
https://www.youtube.com/watch?v=P0Y9sqXAHo0
Figures:
Top: Photos of microcontainers of various shapes (un-filled, spherical, tubes, stars). https://www.youtube.com/watch?v=P0Y9sqXAHo0
Bottom left: Results of in vivo testing. Plasma concentration, measured in in μg/mL, of a drug is plotted against time for the microcontainers (red) and the Eudragit coated capsules used as a control (blue). In both cases, the plasma concentration peaks at <100 minutes, but the microcontainers cause a sustained plasma concentration exceeding 0.5 μg/mL lasting from 200-1400 minutes, whereas the control drops below 0.5 μg/mL after 200 minutes. https://www.youtube.com/watch?v=P0Y9sqXAHo0
Bottom right: Results of in vitro testing. Cumulative release of a model drug, in %, is plotted against time for coated and uncoated detachable microcontainers (D-MCs), where the containers are exposed to a pH of 1.65 from 0-120 minutes then a pH of 6.5 from 120-480 minutes. The coated D-MCs show a plateau until 120 minutes then a sharp increase in cumulative release of the model drug from <20% to 80% at 120 minutes. The uncoated D-MCs show a gradual cumulative release to 55% at 120 minutes then a jump from 55% to 65% at 120 minutes. https://core.ac.uk/reader/112373140
Slides by: Katherine Savard