Research

 

Research theme 

Research interest

• Magnetic nanofluid hyperthermia and its clinical applications in nanomedicine
• Nanomagnetic biometerials and ferrite nanoparticles/Nanofluids for biomedical applications
• Nano-/Microstructures magnetic biosensors and bioMEMS for bioelectronics
• Extremely low frequency electomagnetic devices for therapeutics and healing
• Bioelectromagnetism and bioelectricity for neural engineering and neuromodulation
• Bioinstrumentation/medical electronics & devices for neurodegenerative diseases
• Nano-scale spintronics structures and devices for active/passive digital/analog electronics
• Nanostructure magnetic/electronics thin films and devices

• Designing and processing of materials for spintronics for advanced electronic devices
• Bioelectric/spintronic based hybrid power generators for energy sustainability

Research overview

Nanoscale magnetic materials, which exhibit a variety of unique magnetic phenomenon that is drastically different from those of their bulk materials, are attracting significant interests since these properties can be promisingly used for various biological applications. In the past decade, our research group focused on the development of high-performance superparamagnetic nanoparticles and magnetic thin-film by introducing innovative crystal structure and architecture to the nanoparticles and thin-film structures, respectively. In particular, we optimized surface of nanomaterials by encapsulating them with biocompatible layers for the safe uses of these materials in the medical fields of ultra-sensitive biosensors, non-invasive cancer treatments, high-resolution MRI imaging, and neurodegenerative diseases treatments.  In addition, those nanoparticles are designed to work very low energy range of magnetic field which is harmless to patients.  
 

Figure 1. Research overview

Key technologies of Bae group

Figure 2. We are developing various important techniques for designing of biocompatible magnetic fluid hyperthermia agents, nanostructure spintronics materials and devices for advanced electronicspoint-of-care biosensor platforms, and low-frequency electromagnetic field medical devices. 

 

Research theme 1: 

Artificially-engineered superparamagnetic ferrite nanoparticles/nanofluids and advanced electronics/magnetics bioinstrumentation technology for "Nanomedicine"

Magnetic nanoparticles, particularly superparamagnetic ferrite nanoparticles coated with bio-functional materials/biocompatible polymers with a diameter of 6 ~ 15 nm mean particle size have been and are being paid a considerable attention in nanomedicine, regenerative medicine, thermal nanomedicine, and nano-theranostics, because they have attractive physical, biotechnical, and physiological properties for a variety of clinical applications and treatments: (1) they are chemically stable and are expected to have higher biocompatibility and cell viability, (2) they can easily be injected through a human administrative system, (3) they can be transported to the targeted cells by blood circulation or an external magnetic field (action in distance property), (4) they can differentiate normal cells from malignant or lesion cells using bio-affinity reaction, (5) they can be self-heated under an AC magnetic field, and (6) they can be used for imaging contrast agents by externally applied magnetic field.

Figure 3.  Magnetic nanofluid hyperthermia systems for treating brain tumors. Magnetic nanoparticles (MNPs) can convert AC electromagnetic energy into thermal energy in a non-invasive manner. MNPs injected into the tumor area increase the local temperature and kill the cancer cells. However, this strategy suffers from a low heat inducing capability of MNPs. We developed new types of MNPs to solve this problem by redesigning of MNPs at an atomic level. Our newly developed magnetically softened iron oxide (MSIO) MNPs can induce immense thermal energy (intrinsic loss power (ILP): 14 nH m2 kg−1) in the cancer cells to completely destroy them. In particular, MSIO is operated under a physiologically bio-safe range of AC magnetic field which is our unique technology and is not harmful to patients.

Our research interests/activities financially supported by hospitals, government, and industries in this area were/are focused on two main categories. The first is to develop new ferrite superparamagnetic nanoparticles/nanofluids, which can overcome the critical challenges of magnetic nanoparticles/nanofluids currently facing in various real clinics. The second is to develop new clinical treatment and diagnostic modalities using the developed nanoparticles/nanofluids and advanced electronics/spintronics(magnetics) high-performancebioinstrumentation technology in nanomedicine. Our primary research efforts in this research area include the development of: 1) local magnetic nanofluid hyperthermia systems for treating various tumors (prostate/breast cancer, glioblastoma multiforme (GBM), Figure 3-5), 2) new thermal nanomedicine modality for ocular neuroprotection in glaucoma based on local induction of heat shock proteins (Figure 6), 3) a new type of magnetic antenna designed by magnetic nanoparticles/nanofluids for AC electromagnetic field stimulation and Deep or Repetitive TMS (Transcranial Magnetic Stimulation) for treating neurodegenerative diseases such as Parkinson’s disease, epilepsy, and dystonia etc., 4) heat triggered drug delivery system (DDS) for medications 5) fluorescence coated magnetic nanoparticles/nanfluids for ERG (Electroretinogram) imaging contrast agents, 6) ultra high r2-relaxivity of MRI nanofluid agents for single molecular imaging and sinle cell level cancer diagnosis, 7) a new regenerative medicine modality for cell repairing and retina protection in tissue engineering, 8) a new “Hemostasis modality” based on magnetic nanofluid hyperthermia for efficaciously stopping bone bleeding and curing TBI (Traumatic Brain Injury), and (9) remote control of "neuron signal transmission", and Ca2+ ion open channel physiological properties by AC magnetically-induced thermal stimulation for neuronal engineering and osteoporosis.

 
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Figure 4. Local magnetic nanofluid hyperthermia systems for treating various tumors . a) A schematic diagram of Mg0.13-γFe2O3 nanoparticles synthesis system and their heat emission under AC magnetic field. b)TEM image of Mg0.13-γFe2O3 nanoparticles and a schematic diagram of the spinel structure of Mg0.13-γFe2O3 nanoparticle. c) Comparison of ILP value of our newly developed Mg0.13-γFe2O3 SPNPs to other previously reported superparamagnetic nanoparticles. d) Studies of in vivo magnetic hyperthermia using Mg0.13-γFe2O3 nanofluid with a xenografted animal model.  (Adv. Mater. 2018 / See this paper)
Figure 5. Our research introduced in the Advanced Science News. " A potent magnetic fluid hyperthermia agent for cancer treatment"
Figure 6. Thermal nanomedicine modality for ocular neuroprotection in glaucoma based on local induction of heat shock proteins. a) A schematic diagram of the AC magnetic field with duty cycle during MNFH. The D, duty cycle, is defined as the ratio of the τH to the heat repetition interval (HRI = τH + τR). b) A schematic diagram describing the increased recovery time (τR) can improve the cell survival rate.
(Sci. Rep. 2017 / See this paper)

Research theme 2: 

Nanostructure spintronics materials and devices for advanced electronics

In order to comply with the rapid development of electronics, an ultra-high-speed, an extremely low power consumable, and an ultra-low dimensional (nano-dimension) passive or active devices are essentially required. Accordingly, spintronics devices with nano-patterned structures are currently receiving considerable attention, because these devices can satisfy the urgent requirements that conventional electronics is facing. 
Figure 7. Evaluation of the effect of perpendicular anisotropy on the interlayer coupling.
(Firstly discover for RKKY oscillation coupling)
Figure 8. Current perpendicular to plane device showing the electrodes and the device regions and its GMR characterization with different diameter of the device structure.
 
With regards to this research effort, our research interests were/will be focused on the development of various solid-state nano-patterned spintronics devices including spin-transfer switching MRAM, various spin logic devices, domain-wall switching memory, GMR/TMR spin-filter amplifier, spin voltage stabilizer, Schmitt trigger, and GMR/TMR digital latches. The metallic current-in-plane (CIP) and current-perpendicular-to the plane (CPP) GMR/TMR spin-valves with perpendicular anisotropy were/will be mostly considered for the nano-patterned device elements due to their high magnetic and thermal stability. In addition, magnetic compound semiconductors and transition metals/semiconductor interfaces such as conventional MOS(Metal Oxide Semiconductor) or MIS (Metal Insulator on Sapphire)/nanostructure magnetic or non-magnetic metal thin films were/will be intensively studied for the development of new functional spin injection devices. 
Figure 9. Nanopatterned based pseudo spin-valves for 1Gb magnetic random access memory and its GMR behavior including spin-transfer switching.
Figure 10. Design of gate and amplifier for integrated circuit form, fabricated device, and its out-/input signal
Figure 11. Logic architecture design and fabrication of 8 Kbit magnetic random access memory 
The electrical and magnetic degradation mechanism of nanostructure spintronics were/will be also studied in terms of electromigration, thermomigration, electrostatic discharge, and electrical breakdown to predict the device reliability. In recent, the spintronics researches have been extended to the development of a new type of electrical power generator for energy sustainability. A nanostructure magnetic/non-magnetic double-layered thin film electrical power generator induced by both spin photovoltaic and thermoelectric effects and "spinbiotronics" power generators etc. are included in this research area.
Electromigration (GMR read sensor)
Electrostatic discharge and breakdown (TMR reader)
Figure 12. Investigation of reliability (electronmigration/electrostatic discharge/electrical breakdown) of giant magnetoresistance spin valve sensors.
Figure 13. Magnetically labeled GMR biosensor with single immobilized particle agent for the detection of the extremely low concentration of biomolecules.

Research theme 3: 

Magnetically-labeled immunoassay point-of-care biosensor platforms and nanostructure in-vivo & implantable magnetic biosensors for diagnosis and continuous monitoring

The special requirements and challenges of current biosensor technology used in biomedical application fields for detecting the biological and metabolic signals from the human body are to realize a continuous monitoring in an in-vivo and to build up controlling and power units containing not only sensors but also actuators to eliminate overcompensation effects. In particular, for the treatment of chronic diseases (high blood pressure, and diabetes etc.) and for diseases, which have no effective treatment method (glaucoma, brain stroke, renal failures etc.), the development of in-vivo & implantable biosensors for continuous monitoring of each biological signal and self-controlling is essentially required. The magnetic biosensors based on 1) Giant magnetoresistance(GMR), or tunneling magnetoresistance(TMR) effects, 2) Giant AC magnetoimpedance effects, 3) Anomalous Hall effects, 4) Ferromagnetic resonance, and 5) Giant magnetostriction effects, are considered to be a promising in-vivo & implantable biosensors, because they can be easily patterned in a nano-scale with a higher electrical and thermal stability and integrated with other sub-electronics (signal process, signal conditioner, amplifier etc.) on the same chip by  current nanoelectronics technology. In particular, the LC circuit power generator/power receiver integrating with magnetic biosensors implanted in the human body can make them useful for a long time without changing the battery.
 
Moreover, an in-vitro magnetic biosensor platform, especially GMR (or TMR) and anomalous Hall effects based biosensors with immobilized magnetically-labeled nanoparticle (or microbead) sensor agents have drawn a huge attraction in the lab-on-chip and point-of-care disease diagnostic sensor modules due to their technical advantages: (1) easy retrieval of sensor signals, (2) fast sensor response time and low volume essays, (3) a higher SNR (Signal-to-Noise Ratio), and (4) a higher sensitivity. Regarding this research area, I have made prominent achievements for the last few years at the NUS on the new structure of a GMR biosensor with the specially designed magnetic keeper and the development of a TMR based biosensor platform to successfully diagnose prostate cancer by detecting the cancer-induced DNA deformation and proteins. Currently, I am continuously making huge efforts to develop the new type of multi-channel diagnostic point-of-care biosensors and implantable biosensors to directly detect the biological signals. My current and future research interests include; (1) in-vivo & implantable magnetic pressure biosensors for continuous monitoring of intraocular pressure for glaucoma, aorta valve blood pressure for surgical operation, and intracranial pressure for brain ischemia & cerebral infarction, (2) a variety of point-of-care biosensors to detect an extremely low concentration of viruses (< 50 viruses/ml) or biomolecules (< 10-18 mole) for Sepsis, Food poisoning (Noro virus monitoring), Quantitative analysis of myocardial impaction (Troponin I monitoring), and Influenza A (H1N1 virus).
Figure 14. Characterization of thin film behavior (Villari effect) under mechanical tensile and compressive stress.
 

Research theme 4: 

Nanomagnetics and low frequency electromagnetic field medical devices & bioelectronics for bioelectromagnetism, therapeutics, healings, and neuronal engineering

In order to analyze the bioelectric characteristics and bioelectromagnetic field generated from the human body for accurate diagnosis and efficacious therapeutics in “Biomagnetism or Bioelectromagnetism”, the medical instrument/electronics systems are needed to monitor the bioelectric/bioelectromagnetic signals including biopotential from the human body more safely and precisely. However, although the current biomedical instrument techniques can allow for processing 3D images of bio- and physiological signals and for mapping the clinical conditions of patients, the detection of extremely tiny bioelectromagnetic field in a range of nT(10-5 Oe) (cardiac) ~ fT(10-11 Oe) (brain) using a SQUID (Superconducting Quantum Interference Devices) system is technically limited by the physical characteristics and the operating conditions of SQUID devices: (1) it only detects the bioelectromagnetic field by measuring magnetic flux change per unit area, called by resolution limit, and (2) it needs a special room equipped with magnetic shielding and temperature cooling system. Therefore, the measurement of bioelectromagnetic field generated from tiny area of brain for diagnosis, MEG (Magnetoencephalography), and the evaluation of cardiac physiological conductions from the dynamic measurement of tiny biomagnetic field, i.e. arrhythmia, arterial & ventricle fibrillation, for MCG (Magnetocardiography) etc., essentially require newly designed ultra-high sensitive and extremely low frequency magnetic field (or electromagnetic field) devices with multi-arrayed architectures, which can detect an ultra-low field in the range of 10-5 ~ 10-11 Oe/. With regards to this research area, my current research activities are emphasized to develop a new type of nanostructure magnetic multifunctional biomedical devices/instrumentation using TMR & GMR spin-valves with spin-transfer torque effects substituting for current SQUID-based MEG, MCG, and MGG etc. Designing a new close-flux gate structure for an effective magnetic/electromagnetic shield and integrating with high density device arrays, which can allow for detecting a magnetic field as low as below 10-5 Oe/, are mainly included in this research effort. In addition, this research effort related to the development of nanomagnetics and low frequency electromagnetic field (including extremely low frequency electromagnetic field) devices and systems for medical electronics are/will be extended to the various bioinstrumentation and bioelectronics technologies for therapeutics, healings, and neuronal engineering related clinical treatment modalities: (1) Extremely low frequency electromagnetic field medical devices/bioinstrumentation for arthritis therapeutics and muscle pain relief, (2) Control of bone resorption/formation by pulsed electromagnetic field (AC bioelectronics) for osteoporosis and rehabilitation, (3) AC electromagnetic field/AC electric field treatments by non-invasive contact/non-contact electrodes for brain tumor (mostly glioblatoma multiform (GNM)) growth inhibition, (4) Hyper (high temperature)/cryogenic surgical bioinstrumentation (or medical devices for surgical operation) based on nanomagnetics materials and devices, and (5) Wireless-implantable Deep DBS systems embedded with a power transmitter, a pulse generator, and a control feedback circuit in a single chip as well as Deep or Repetitive TMS systems with a new type of implanted magnetic antenna for treating neurodegenerative diseases, are/will be actively studied in this research field.

Figure 15. The detection range of various magnetic field sensor and challenges of GMR/TMR sensors in medical instrumentation applications 
Figure 16. Extremely low magnetic field tunneling magnetoresistance sensor for magnetocardiography.
 

Research grants

After joining the University of South Carolina

         1) "In-vitro and In-vivo medical feasibility and bio-availability tests of biocompatible polymer coated Mg shallow doped γ-Fe2O3
              nanofluids for pre-clinical and clinical hyperthermia applications"

              SOUTH KOREA, PI, (Nov. 2018 ~ Oct. 2020), USD $ 798,510

         2) "Development of alkali metals and alkali earth metal ions doped γ-Fe2O3 superparamagnetic nanoparticles with colossal intrinsic

              loss power and exceptionally high r2-relaxivity of MR imaging for cancer “Nanotheranosis”"

              SOUTH KOREA, PI, (Jan. 2018 ~ Jan. 2020), USD $ 900,000

         3) "Thermoablation of glioblastoma (GBM) brain tumors by magnetic nanofluid hyperthermia with gigantic induction heating power"

               NIH, currently pending  PI, (Submitted in Nov. 2017), USD $2,510,462

         4) "MRI imaging-guided drug delivery system heat triggered by AC magnetic induction for brain tumors"

               NIH, currently pending, PI, (Submitted in Nov. 2016), USD $2,492,700

         5) "Superparamagnetic ferrite nanofluids with exceptionall y high r2-relaxivity for single molecular imaging and highly efficient cell

              tracking in tissue engineering"

              NSF-South Carolina Experimental Program to Stimulate Competitive Research (EPSCO), Participant PI, (Jan. 2016 ~ Jun. 2016),

              USD $ 100,000

         6)  "Synthesis of superparamagnetic nanoparticles and its applications in biomedicine"

               Start-up funding from College of Engineering and Computing, USC, PI, (Aug. 2015 ~ July 2018), USD $ 260,000

Before joining the University of South Carolina (National University of Singapore, 2004 ~ 2013)

         1) "A new electrical magnetic thin film power generator and its integration in nano-scale for a renewable energy system"

              PUROTECH Co. Ltd., SOUTH KOREA, PI, (Dec. 2012 ~ Jun.  2013), USD $ 254,450.0

         2) "Integrative Program on Commercialization of Nanomedicine & Theranosis Modalities for glaucoma, neural diseases (Perkins’s

              disease, Epilepsy, & Brain strokes) and cancers (glioblastoma, Hepatic cancer, and Lung cancer) using magnetic nanoparticles and   

              smart magnetoelectronics technologies"

              Nuri-Vista Co. Ltd., SOUTH KOREA, PI & Program Leader, (Jan. 2011 ~ Apr. 2012), USD $ 5,124,338.8

         3) "Engineered superparamagnetic nanoparticles for neuroprotection – Modulation of intraocular nanoparticle delivery to optic nerve"

              Seoul National University of Hospital (SNUH), SOUTH KOREA, Co-PI, (Apr. 2010 ~ Mar. 2011), USD $ 30,000.0

         4) "CCP-CPP GMR spin-valve read sensors with Fe3O4 nanoparticle insertion for 10 Tbit/in2 recording density (I)"

              Daion Co. Ltd., SOUTH KOREA, PI, (Jan. 2009 ~ Jan. 2014), USD $ 787,826.0

         5) "Integrative program of nanomedicine through development, translation and clinical applications"

              Seoul National University of Hospital (SNUH), SOUTH KOREA, Co-PI, (Jul. 2009 ~ Jun. 2011), USD $ 128,795.0

         6) "Induction of ocular neuroprotection using magnetic nanoparticles – Biocompatibility and intracellular transport of magnetic

              nanoparticles in vitro"

              Seoul National University of Hospital (SNUH), SOUTH KOREA, Co-PI, (Jul. 2008 ~ Jun. 2009), USD $ 10,000.0

         7) "Spin transfer switched 1 Gbit magnetoresistive random access memory (MRAM) based on perpendicularly magnetized

              magnetic tunnel junctions (MTJs)"

              A-STAR, PSF funding, SINGAPORE, PI, (Jan. 2006 ~ May 2009), USD $ 656,667.2

         8) "Development of TMR based biosensors using DNA coated Co-ferrite magnetic particles"

              LG Micron Co. Ltd., SOUTH KOREA, PI, (Sep. 2005 ~ Mar. 2009), USD $ 340,021.8

         9) "Physical study of electromigration-induced failure mechanism of nano-structured current perpendicular to the plane (CPP)

              giant magnetoresistance spin-vale read sensors"

              FRC, SINGAPORE, PI, (Apr. 2005 ~ Mar. 2009), USD $ 131,281.0

         10) "Effects of half-metallic insertion layer on GMR ratio enhancement and area resistance change in nanostructured CCP-CPP

               GMR spin-valves"

               INSIC, Funding, USA, PI, (Sep. 2005 ~ May. 2006), USD $ 11,000.0

Bae group, Department of Electrical Engineering, University of South Carolina