Freddy T. Nguyen, MD, PhD

Research Fellow @ Massachusetts Institute of Technology, Transfusion Medicine Fellow @ Dartmouth-Hitchcock Medical Center

Publication

Emerging technologies in cancer detection

Exciting, modern technologies for cancer detection are under development in academic and industrial laboratories worldwide. This chapter provides a synopsis of technologies reaching greater importance as they advance toward clinical practice. These methods include significant advances in current methods as well as fundamentally new platforms. We place a special emphasis on point-of-care technologies for use in clinical settings as well as novel methods for use as at-home measurements and wearable devices. We also provide a synopsis on the involvement of artificial intelligence-based data analytics such as machine learning algorithms in both existing and developing assessments.

Publication

A wavelength-induced frequency filtering method for fluorescent nanosensors in vivo

Fluorescent nanosensors hold the potential to revolutionize life sciences and medicine. However, their adaptation and translation into the in vivo environment is fundamentally hampered by unfavourable tissue scattering and intrinsic autofluorescence. Here we develop wavelength-induced frequency filtering (WIFF) whereby the fluorescence excitation wavelength is modulated across the absorption peak of a nanosensor, allowing the emission signal to be separated from the autofluorescence background, increasing the desired signal relative to noise, and internally referencing it to protect against artefacts. Using highly scattering phantom tissues, an SKH1-E mouse model and other complex tissue types, we show that WIFF improves the nanosensor signal-to-noise ratio across the visible and near-infrared spectra up to 52-fold. This improvement enables the ability to track fluorescent carbon nanotube sensor responses to riboflavin, ascorbic acid, hydrogen peroxide and a chemotherapeutic drug metabolite for depths up to 5.5 ± 0.1 cm when excited at 730 nm and emitting between 1,100 and 1,300 nm, even allowing the monitoring of riboflavin diffusion in thick tissue. As an application, nanosensors aided by WIFF detect the chemotherapeutic activity of temozolomide transcranially at 2.4 ± 0.1 cm through the porcine brain without the use of fibre optic or cranial window insertion. The ability of nanosensors to monitor previously inaccessible in vivo environments will be important for life-sciences research, therapeutics and medical diagnostics.

Publication

Implantable Nanosensors for Human Steroid Hormone Sensing In Vivo Using a Self-Templating Corona Phase Molecular Recognition

Dynamic measurements of steroid hormones in vivo are critical, but steroid sensing is currently limited by the availability of specific molecular recognition elements due to the chemical similarity of these hormones. In this work, a new, self‐templating synthetic approach is applied using corona phase molecular recognition (CoPhMoRe) targeting the steroid family of molecules to produce near infrared fluorescent, implantable sensors. A key limitation of CoPhMoRe has been its reliance on library generation for sensor screening. This problem is addressed with a self‐templating strategy of polymer design, using the examples of progesterone and cortisol sensing based on a styrene and acrylic acid copolymer library augmented with an acrylated steroid. The pendant steroid attached to the corona backbone is shown to self‐template the phase, providing a unique CoPhMoRE design strategy with high efficacy. The resulting sensors exhibit excellent stability and reversibility upon repeated analyte cycling. It is shown that molecular recognition using such constructs is viable even in vivo after sensor implantation into a murine model by employing a poly (ethylene glycol) diacrylate (PEGDA) hydrogel and porous cellulose interface to limit nonspecific absorption. The results demonstrate that CoPhMoRe templating is sufficiently robust to enable a new class of continuous, in vivo biosensors.

Publication

Optical coherence tomography and targeted multi-modal protein microspheres for cancer imaging

The field of biomedical optics has grown quickly over the last two decades as various technological advances have helped increase the acquisition speeds and the sensitivity limits of the technology. During this time, optical coherence tomography (OCT) has been explored for a wide number of clinical applications ranging from cardiology to oncology to primary care. In this thesis, I describe the design and construction of an intraoperative clinical OCT system that can be used to image and classify breast cancer tumor margins as normal, close, or positive. I also demonstrate that normal lymph nodes can be distinguished from reactive or metastatic lymph nodes by looking at the difference in scattering intensity between the cortex and the capsule of the node. Despite the advances of OCT in the detection and diagnosis of breast cancer, this technology is still limited by its field of view and can only provide structural information about the tissue. Structural OCT would benefit from added contrast via sub-cellular or biochemical components via the use of contrast agents and functional OCT modalities. As with most other optical imaging techniques, there is a trade off between the imaging field of view and the high-resolution microscopic imaging. In this thesis, I demonstrate for the first time that MM-OCT can be used as a complimentary technique to wide field imaging modalities, such as magnetic resonance imaging (MRI) or fluorescence imaging, using targeted multi-modal protein microspheres. By using a single contrast agent to bridge the wide field and microscopic imaging modalities, a wide field imaging technique can be used to initially localize the contrast agent at the site of interest to guide the location of the MM-OCT imaging to provide a microscopic view. In addition to multi-modal contrast, the microspheres were functionalized with RGD peptides that can target various cancer cell lines. The cancer cells readily endocytosed bound protein microspheres, revealing the possibility that these protein microspheres could also be used as therapeutic agents. These investigations furthered the utility of the OCT technology for cancer imaging and diagnosis.

Nanotube-porphyrin molecular structure and applications of same
Patent

Nanotube-porphyrin molecular structure and applications of same

A molecular structure. In one embodiment, the molecular structure includes a nanotube formed With a plurality of carbon atoms having a first end, an opposite, second end, and a body portion defined there between, wherein the body portion has an interior surface defining a cavity, an opposite, exterior surface and a longitudinal axis therethrough the cavity, and a porphyrin molecule having a plurality of carbon atoms and a first plurality of hydrogen atoms, wherein at its original state the porphyrin molecule has a plurality of pyrrole units and each pyrrole unit is coupled to another pyrrole unit through a methine bridge so as to form a ring structure with a second plurality of hydrogen atoms positioned peripherally along the ring structure. The porphyrin molecule is chemically coupled to the interior surface of the nanotube such that at least one of the second plurality of hydrogen atoms positioned peripherally along the ring structure is replaced by a carbon atom of the nanotube.

Computational Analysis of Transition Metal Doped Nanotubes and Their Application to Molecular Electronics

We have previously proposed molecular circuits designed from polyaniline polymer strands, polyacetylene polymer strands and charge transfer salts acting as transistors. Due to unique properties that are demonstrated in this manuscript, we propose the use of carbon single wall nanotubes and transition metal endohedrally doped single wall carbon nanotubes (SWNTs) for utilization in molecular electronics. Different transition metals were used in a systematic fashion to manipulate the molecular orbital energy gap (HOMO-LUMO gap) of metallic (Ch = (n = m)) nanotubes. Gradient corrected, Density Functional Theory (DFT) Self Consistent Field (SCF) calculations were used to calculate molecular orbital energy levels, HOMO-LUMO gaps, electron affinities, ionization energies and other electronic properties for these molecules. The effect that a SWNT’s length has on its HOMO-LUMO gap was investigated. DFT-SCF calculations were also used to demonstrate how multiple metal filled nanotubes could be used to construct a molecular nanotube based transistor.

Electron transfer to oriented molecules: Surprising steric effect in t-butyl bromide

Collisions between neutral K atoms and oriented t-butyl bromide molecules produce the ions K+ and Br− at energies high enough to separate charged particles (≳4 eV). Ions are detected by coincidence tof mass spectrometry for orientation of the t-butyl bromide such that the K atom attacks either the Br end or the t-butyl end of the molecule. At high energies the steric asymmetry factor is larger than that for CH3Br. But at energies near threshold, the steric asymmetry factor reverses sign and attack at the t-butyl end becomes more reactive than attack at the Br end. The electron is apparently transferred into different orbitals at different ends.

Physician-scientist with extensive experience developing and translating nanotechnologies and biomedical optical technologies from the bench to clinic in areas of genetics, oncology, and cardiovascular diseases. Extensive experience in community building in healthcare innovation, research, medical, and physician-scientist communities through various leadership roles.

Research Profiles

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