Surface-Tethered Antimicrobial Peptides
The AMProtection patent-pending coating is comprised of the covalent attachment of antimicrobial peptide (AMP) Chrysophsin-1 onto a surface using a linker molecule. These AMPs utilize unique mechanisms against bacteria, making them broadly antimicrobial with a low likelihood of resistance. Catheter-associated urinary tract infections (CAUTIs) cause 12-25% morbidity in patients and start at $1,000 per case; thus, the best course is to prevent their occurrence. Preventative competing methods include catheters dip-coated with silver, traditional antibiotics or chemical antiseptics. However, several recent studies had called the effectiveness of silver into question, whereas desorption of antibiotic- and antiseptic-coatings causes a higher chance of antibiotic resistance and toxic side effects. The AMProtection innovation is differentiated because it is broad-spectrum, surface-tethered (therefore will not release from the surface), biocompatible, and does not promote resistance. The potential impact on the urinary catheter market, which is $1 billion in the U.S., half of which are antimicrobial coated catheters, depends on the licensee (for example, BARD owns 85% of the market share). However, we expect that per 10,000 coated catheters sold, we reduce 80% of CAUTIs, 200 patient hospital days, and tens of millions of dollars in unreimbursed never event expenses.
Shijiazhuang, Hebei Province
Novel therapy for neuroprotection in Parkinson's disease by TiO2 nanowired DL-3-n-butylphthalide (DL-NBP)
The role of DL-3-n-butylphthalide (DL-NBP), one of the constituents of Chinese celery extract in Parkinson’s disease (PD) is not known. In this innovation, neuroprotective effects of DL-NBP in PD after concussive head injury (CHI) on brain pathology were found in a mice model. CHI was inflicted in in control or PD model by dropping a weight of 114.6 g from a height of 20 cm inducing an impact of 0.224 N on right parietal skull. PD like symptoms was induced by injections of 1-metyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP, 20 mg/kg) daily within 2-h intervals for 5 days. DL-NBP was administered (60 mg/kg, i.p.) 4 h after CHI. In addition, TiO2-nanowired delivery of DL-NBP (40 mg/kg, i.p.) were also given in identical conditions. Untreated CHI with PD showed profound increase in blood-brain barrier (BBB) breakdown, edema formation and neuronal injuries 24 h after CHI. Treatment with DL-NBP slightly reduced brain pathology in CHI in PD mice whereas TiO2-DL-NBP was effective in reducing brain damage by only 40 mg dose in CHI. This innovation shows that DL-NBP reduces brain pathology in PD with CHI but nanodelivery of DL-NBP is far more superior for neuroprotection in PD+CHI model.
Microfluidic Polymer Droplet for Drug Delivery and Therapeutic Applications
Microencapsulation of cells in semi-permeable polymer networks is a promising approach for avoiding immunosuppressive therapy in allogeneic, xenogeneic and genetically modified cell transplantation. Current technology uses an electrostatic droplet generator and alginate-based polymers. Major drawbacks to this system are that cellular microspheres are limited to larger diameter sizes (>200 micrometers) and alginate-based polymers provide minimal control over the cellular microenvironment. By utilizing advanced synthetic polymers, bioactive molecules can be chemically conjugated, and the cellular microenvironment can be fine-tuned based on therapeutic application. demonstration that hydrogel microspheres using biocompatible synthetic material can encapsulate viable cells and bioactive molecules using a novel microfluidic droplet system. Cells, biomolecules, and drugs are suspended in liquid polymer solution and then extruded in droplet-form via microfluidics into a continuous phase solution containing an oil-crosslinker mixture. This unique method creates well-defined structures that allow for quick reactions and in situ delivery to the patient. The microspheres are comprised of biocompatible polyethylene glycol-based (PEG) polymer, and the diameter size of the beads can be fine-tuned by adjusting the nozzle dimensions and flow rates of the microfluidic droplet system. The hydrogel microspheres and their degradation by-products are non-toxic and do not elicit an inflammatory response.
Hydrogels to Treat Bone Fracture and Orthopedic Device Infections
Background: Orthopedic hardware infections are a significant clinical problem with artificial joint replacement surgeries. The most common bacterial infections are caused by Staphylococcal aureus (S. aureus) and current treatments are limited to surgical debridement and systemic antibiotic regimens. Infections almost always lead to implant removal. Lysostaphin enzymes have been shown to have high anti-Staphylococcal activity and thus their use to reduce infection of biomaterials associated with orthopedic implants could have significant health benefits. Technology: Inventors at Georgia Tech engineered a lysostaphin-delivering injectable hydrogel to treat S. aureus infections in bone fractures and orthopedic device implantations. The injectable hydrogel conforms and adheres to the fracture and surrounding tissue, ensuring efficient, local delivery of lysostaphin. This injectable hydrogel formulation enhances lysostaphin stability and provides improved efficacy against bacteria growing in biofilms compared to soluble enzymes alone. Lysostaphin-delivering hydrogels effectively eliminate orthopedic S. aureus infections while simultaneously supporting fracture repair.
Electronic Sensor for Multiplexed Detection of Particles on Microfluidic Chips
Technology: Inventors at Georgia Tech have developed a novel system of parallel detection in multiple microfluidic channels which relies on code division multiple access (CDMA), a spread spectrum telecommunication technique. In CDMA, users’ signals are transmitted at the same time and within the same frequency band, while multiplexing is achieved by modulating the information in each channel with a unique digital spreading code. The set of CDMA digital spreading codes are designed to be orthogonal to minimize the cross-correlation while maximizing the auto-correlation. The technology has been demonstrated on four microfluidic channels encoded by 7-bit long Gold sequences. The chip has only three electrodes: a positive and a negative electrodes on the opposite sides of each microfluidic channel (ordered to follow their unique digital spreading code) and a reference electrode placed in between the coding fingers, used to generate a bipolar signal. The system successfully detected the presence of multiple ovarian cancer cells in the channels and could even resolve their timing.
Synthetic Hydrogel for Human Organoid Generation
Background: In vitro generation of human intestinal organoids (HIOs) from pluripotent stem cells is a powerful technique capable of producing tissue analogous to human tissue for basic studies, drug screening, and regenerative medicine. Current methods for generating HIOs rely on growth in Matrigel, a murine tumor-derived extracellular matrix (ECM). Due to the composition and variability of Matrigel and its tumor-derived nature, this method severely limits the use of organoid technologies for regenerative and translational medicine. There is a need for an alternative method of producing HIOs for use in human therapeutic applications. Technology: Inventors at Georgia Tech and the University of Michigan have engineered a fully synthetic and chemically defined hydrogel that supports in vitro generation of human organoids. The hydrogel supports robust and highly reproducible in vitro growth and expansion of HIOs. Additionally, this synthetic hydrogel serves as an injectable vehicle to deliver HIOs to intestinal wounds via colonoscope resulting in organoid survival, engraftment, and wound repair.
Two-stage delivery and release drug delivery system
Background: Current drug delivery methods employ small therapeutics, which do not exhibit prolonged systemic circulation or efficiently accumulate in target tissues. In order to surpass these barriers, researchers must improve conjugation efficiency and understand the rate of different therapeutics, as well as take into consideration assessments of toxicity and immuno-genicity. Technology: This technology combines the advantage of nano-particle drug delivery for improving targeting performance with time-based release of cargo in order to achieve targeted therapeutics delivery. Whereas previous technology failed to surpass barriers of conjugation and timing, this system can deliver a variety of particles systemically or to deep tissues such as tumors or lymph nodes, through the utilization of nano-particles and an oxanorbornadiene linkage chemistry that degrades at programmable half-lives.
Sutures with Porous Sheaths for Drug Delivery
Technology: Georgia Tech inventors have developed a simple and versatile method for creating highly porous sutures which aim to accelerate the healing process of an injury site. These sutures are modified to contain an interconnected network of pores, serving to increase the volume of drug loading and allowing for the sustained release of the drug into the affected area. Compared to unmodified suture implants, the porous sutures have the same mechanical properties, but with enhanced drug loading capacity and a sustained release profile of the loaded drug. The modification process of the sutures is simple and conducted in liquid phase at room temperature with low-cost reagents, allowing for easy scale-up in commercial production. The porous sutures not only release drugs for anti-inflammatory, anti-microbial, and pain management purposes, but other bio-factors, such as growth factors, adhesives, extracellular matrix components, and cytokines, can be released to facilitate efficient tissue restoration and would healing. This novel invention also has great potential for the repair of load-bearing connective tissues, such as tendons, and can be readily extended to other applications for wound closure and long-term pain relief post-surgery.
Microgel Constructs for Tissue Repair and Regeneration
Background: Fibrinogen is a soluble plasma protein that is converted to insoluble fibrin fibers in response to damage to the vascular system. The temporary fibrin matrix promotes cell adhesion, migration, and proliferation, which are essential to wound healing. Bioengineered fibrin gels are used to promote wound healing in various clinical applications. However, most commercially available fibrin gels do not fully match the mechanical properties of the target tissues. High concentrations of protein inhibit cellular infiltration and biomaterial integration. Low concentrations of protein result in gels with weak mechanical strength that are not practical for clinical use.The ideal fibrin material would be both permissive to cell infiltration and regeneration while retaining mechanical properties appropriate to each specific application. Technology: A hybrid fibrin-microgel constructs for enhanced cell infiltration and wound healing applications. Proof of concept studies show that incorporating microgels (hydrogel microparticles) into fibrin gels generates a more porous matrix while maintaining its mechanical properties. Microgels form unique interconnected structures within the fibrin matrix, allowing for enhanced cell infiltration, remodeling, and regeneration, when compared to currently available fibrin gels.These hybrid constructs can also be used to deliver therapeutic, diagnostic, nutraceuticals, prophylactic, and cosmetic agents to a desired site.
Antibody Coated Nanoparticle Vaccines
Background: Vaccine development is considered one of the most successful public health interventions in history. The challenge of safely enhancing new vaccines’ immunogenicity presents an exciting opportunity for bringing cutting-edge immunoengineering research into the clinic. While pathogen-derived adjuvants present a variety of safety concerns that limit their clinical application, human-derived adjuvants can leverage our emerging understanding of the immune system to generate safe and protective immune responses. Technology: Julie Champion and Timothy Chang from the School of Chemical and Biomolecular Engineering at Georgia Tech have designed a novel nanoparticle vaccine delivery system that incorporates antibodies as human-derived adjuvants to enhance the immune response of protein nanoparticles. Proof-of-concept studies utilized model ovalbumin protein nanoparticles coated with immunoglobulin M (IgM). In vivo mouse studies showed that the IgM coating significantly enhanced anti-viral Th1 and memory T cell responses compared to uncoated ovalbumin nanoparticles. While protein nanoparticles were used as a proof-of-concept, this antibody coating platform technology could theoretically be adapted to any type of vaccine particulate, including currently-licensed inactivated pathogen vaccines, to boost and extend the lifetime of protective anti-viral Th1 responses.
Wearable Technology for Cardiovascular Activity
Background: Cardiovascular disease is responsible for one in every four deaths in the US with almost half of all sudden cardiac deaths occurring outside of the hospital. Continuous heart monitoring has the potential to improve the quality of life for individuals with cardiovascular disease and potentially enable early detection and preventative care. Ballistocardiography (BCG) is a non-invasive method of measuring small movements of the body induced by the heartbeat. Technology:Inventors at Georgia Tech have developed a novel non-invasive detection method for central and peripheral cardiovascular activity using BCG. The method estimates center-of-mass BCG, a measure of the displacement of the body’s center of mass, with an accelerometer placed on the surface of the skin and a simultaneously-acquired electrocardiogram. The accelerometer could be placed on most areas of the body including the wrist (smart watch), arm (smartphone armband), chest (chest strap) or forehead (headband). The method has been demonstrated in measuring central hemodynamic force from the wrist. Measuring central hemodynamic forces from distal locations on the body, such as the wrist, could enable cuff-less blood pressure measurement from pulse-transit time and beat-by-beat wearable hemodynamics assessment.
Degradable Microparticles for Protein and Small Molecule Delivery
Background: Loading small molecules and proteins for injection happens on a minute scale and is essential for progress in many medicinal fields. However, the science thus far has been restricted by the size and charge of the molecules, as well as maintaining their activity on the carrier. In addition, many systems require complex and/or expensive injection tools, and the timed release of the medicine throughout the body is difficult to control. Technology: Georgia Tech inventors from the Department of Biomedical Engineering have developed a microparticle delivery system formed via water and oil emulsion and free radical polymerization. The cross-linking of functionalized heparin within the micro-particle allows for the loading and release of positively-charged proteins, as well as variety of small molecules. The polymers utilized also allow for the degradation time course of the particle to be finely tuned.
3D Printed Meta-material Tissue-Mimicking Phantoms
Patient-specific tissue-mimicking phantoms have a wide range of biomedical applications including validation of computational models and imaging techniques, medical device testing, surgery planning, medical education, doctor-patient interaction, etc. Although 3D printing technologies have demonstrated great potential in fabricating patient-specific phantoms, current 3D printed phantoms are usually only geometrically accurate. Mechanical properties of soft tissues can merely be mimicked at small strain situations, such as ultrasonic induced vibration. Under large deformation, however, the soft tissues and the 3D printed phantoms behave differently. The essential barrier is the inherent difference in the stress-strain curves of soft tissues and 3D printable polymers. Georgia Tech inventors have developed technology that demonstrates the feasibility of mimicking the mechanical strain stiffening behavior of soft tissues using dual-material 3D printed metamaterials with micro-structured reinforcement embedded in soft polymeric matrix. Although the two base materials are strain-softening polymers, both finite element analysis and uniaxial tension tests indicate that two of those dual-material designs are able to exhibit strain-stiffening effects as a metamaterial. Additionally, the design parameters have an effect on the mechanical behavior of the metamaterials. this system can fabricate patient specific tiss. ue-mimicking phantoms with both geometrical and mechanical accuracies with dual-material 3D printed metamaterials.
A 3D printed, weight bearing implant for cartilage restoration in the knee
The implantable medical device being commercialized by Nanochon is intended to treat cartilage damage in the knee for young and active patients. Specifically, injuries sustained by adults under 55 to the articulate surface of the knee do not heal. In patients older than 55 cartilage damage and loss is treated with a total joint replacement. However, these have a limited lifespan (15 years average) and are more difficult to replace as their success relies on having a substantial amount of healthy bone tog raft the implant into. Thus, younger patients must undergo procedures to try to salvage remaining tissue in the joint, mitigate degenerative damage and give the patient extended activity. As described, young and active patients are treated with a series of surgical procedures, implants based on processed cadaver tissue, living tissue transplants and complex devices incorporating biologics and live cells. Among all of these treatments, there is none which has a high early success rate, good long term outcomes and is cost-effective. The Nanochon device, using innovative nanomaterial and 3D printed designs, would provide a more successful, longer lasting and affordable solution.
Urea Electrolysis as a Medical Devices Platform
In clinical diagnostics, monitoring urea in blood provides information on kidney’s disease with the normal range of urea level in serum ranges from 1.7mM to 8.3mM. However, under pathological conditions, urea levels in blood can reach up to 100 mM. Currently most urea sensors utilize immobilized urease to catalyze urea decomposition into ammonia, hydroxide, and bicarbonate ions. On the other hand, a universal urea sensor that can operate with different interchangeable working and reference electrodes in a variety of conditions would be useful as it provides stability and flexibility. Furthermore, the technology that this device is based on could serve as a foundation for portable dialysis machines. This is because the technology is based on urea electrolysis - conversion of urea into benign molecules - and is the basis for both detection and conversion of the urea molecule. The use of this technology would deliver a smaller footprint, decrease in water consumption, reduction in cost and improvement and extension of patient life.
TUSK Advanced Tracheal Intubation Stylets
Management of the airway is the first critical step in lifesaving. Seconds matter when it comes to getting oxygen to the heart and brain. Operator difficulty inserting breathing tubes (AKA: endotracheal tubes or ETT’s) translates directly to patient complications. 1st pass success is essential. Operators insert ETT's using a device that exposes the vocal cords (a laryngoscope) and a removable stiffening stylet that’s inserted into the ETT. Increasingly, video-assisted laryngoscopes are being utilized, resulting enhanced exposure of the vocal cords. However, despite better views of the cords, video laryngoscopy often makes the process of inserting of the ETT into the trachea (cannulation) more challenging. As a result, enhanced vocal cord views for operators have not resulted in an incremental improvement in airway management success. Our iterative design process, fueled by user feedback, has resulted in a novel stylet technology with a unique, ergonomic and ETT insertion mechanism resulting easier and faster tracheal intubation that is more conducive to single-operator use. The device lowers the expertise threshold, resulting in safer care in all environments. Our technology can be used with video or traditional laryngoscopy, and can be utilized in adult, child, and veterinary applications.
Contact Lens with Transparent Biosensor Array
A wide range of diagnostic potential exists through monitoring tears in the human eye. Continuous monitoring of chemicals, metabolites, proteins, antibodies, and other biomarkers in tears are of interest since tears are readily assessable and a less complex body fluid compared to serum or plasma. Previous attempts to integrate biosensors into contact lenses has been limited to only one or two sensors, that were externally powered and were obstacle in seeing clearly due to their non-transparent nature. Further, the non-transparent nature of associated components of the biosensors such as antenna, controller circuitry, storage system, etc. limit functionality of integrating biosensors into contact lens by blocking vision. This technology integrates transparent sensors into a contact lens to detect, for example, glucose concentrations in tear fluid. The sensor array is extremely sensitive, reliable, and reversible, and because the sensors are transparent, multiple sensors can be deposited across the field of vision on the contact lens.
Genetic incorporation of tetrazine amino acids and use in bioorthogonal ligations
Ideal bioorthogonal reactions containing high reaction rates, high selectivity and high stability would allow for stoichiometric labeling of biomolecules in minutes and eliminate the need to washout excess labeling reagent. Currently no general method exists for controlled stoichiometric or sub-stoichiometric labeling of proteins in live cells. To overcome this limitation we have developed a faster more stable tetrazine-containing amino acid (Tet-2.0) and have genetically encoded this amino acid in response to an amber codon. We have demonstrated that in vivo reactions between protein containing Tet-2.0 and sTCO react with a biomolecular rate constant of 87,000±1440 M-1s-1. This bioorthogonal reaction is fast enough in cells containing Tet-v2.0-protein with sub-stoichiometric amounts of sTCO-label to remove the labeling reagent from media in minutes thereby eliminating the need to washout label. This ideal bioorthogonal reaction will enable the monitoring a larger window of cellular processes in real time.
PxTx has developed an innovative disease modifying therapeutic technology to treat osteoarthritis (OA). Extracellular Matrix Protection Factor (ECPF-1) is a novel, safe and effective intra-articular injection that reduces the pain and damage caused by OA. Intra-articular injections of ECPF-1 (PEXAGEN) in a rat model of OA demonstrated no cellular toxicity, normal serum chemistry, diminished tissue destruction and increased animal mobility. Currently, there are only a small number of potential disease-modifying osteoarthritis drugs (DMOADs) in clinical trials. ECPF-1's demonstrated efficacy is novel because development of DMOADs with limited off target effects is challenging due to the complexity of the articular joint. Our first commercialization target is the companion animal market, because OA statistics in the canine population mimic that of the human population. In 2016, the global market for animal health amounted to some 30 billion U.S. dollars. Ten years earlier, the market stood at only 16 billion U.S. dollars. The global animal health/veterinary medicine market includes both animals used for food production, and companion animals or pets.
Novel Biodegradable and Non-biodegradable 3D Printed Implants as a Drug Delivery System
In United States, the current gold standard for treatment of infection after total knee arthroplasty is a 2-stage process whereby the implant is removed and temporary spacer made of PMMA (bone cement) with antibiotics is inserted. The patient receives a 6-8 week course of intravenous antibiotics, and then returns to surgery for a re-implantation of a new joint replacement. Unfortunately, PMMA as a drug delivery material has limitations in terms of mechanical and drug-eluting properties. Furthermore, the polymerization reaction for PMMA is highly exothermic, thereby limiting the variety of antibiotics used for the treatment of infections. We have invented a family of 3D printed orthopaedic implants that not only overcome the limitations of PMMA, but can also be designed to be load bearing and customized to individual patient needs. Our implants are ‘smart’ since they incorporate built-in design features such as micro-channels and reservoirs that enable them to act as antibiotic delivery vehicles.
3D Printing Embedded Nanofibers with an Automated On-the-fly Manual Pull Post-drawing System
With the addition of an automated on-the-fly manual pull post-drawing system to a 3D printing machine, nanofibers are stretched and aligned immediately encapsulating within the printed layer. The continuous automated manual pull post-drawing system is inexpensive with a straightforward interchangeable track for different types of polymers. The track can be disposable or lined as a single-use device for bioengineering labs and health care providers. Using this system, the automated spinning track system can produced nanofiber from a wide variety of polymers (ex. PAN, PCL, PEO, PEDOT:PSS, PVAc, PVDF, nylon, para-aramid, telfon nanofibers, etc...), biopolymers (ex. Silk fibroin, collagen, zein, soy, peanut, etc...), DNA, and polymeric carbohydrates (alginate, cellulose, lignin, etc...). The spinning device could enable us to create a wound dressing out of biocompatible materials seed and grow stem cells on scaffolding for tissue engineering. Other examples include biosensors, lightweight composites, filtration technologies, fibrous smart textiles, and battery (fuel cell) technologies. Unlike electrospinning nanofibers (the device uses a mechanical stretching force is used instead of electrical power, making high electrical voltage unnecessary, avoiding high cost, and excessive energy usage during production.
A nontoxic and novel way to prevent and treat cancer and inflammatory disease
We examined the expression of every single gene to find the most promising targets we can use to prevent and treat cancer. Our immediate efforts utilize our lead compound (called “MASL”) to target a unique receptor (called “PDPN”) on cancer cells. PDPN promotes cancer motility, invasion, and metastasis. We can use MASL to prevent and treat many forms of cancer. In addition, PDPN promotes inflammatory destruction leading to rheumatoid and osteoarthritis. MASL can be used to prevent and treat disease in addition to cancer.
Microarray plates – arrayable acoustic actuators for microfluidics
This technology relates to arrayable acoustic actuators that are useful for addressing and acoustically actuating individual wells or compartments of multi-well or multi-compartment microfluidic devices, such as microarray slides or trays, microtiter plates, multi-well slides, etc. It enables retrofitting of acoustic microfluidic actuators to existing standard laboratory tools such as 96- and 384-well microarray trays to allow various functions to be performed such as mixing and sample pre-concentration, to sample ejection and fluid transfer into lab equipment such as mass spectrometers enabling non-contact liquid handling. The technology enables this to be done individually on-demand from the wells in a microarray plate. The present technology takes the opposite approach to conventional instruments by employing an interdigital transducer formed on a non-piezoelectric material which produces an electric wave, that, when brought into contact with a piezoelectric material can, in turn, produce an acoustic wave which also can be utilised to actuate liquid drops (or liquids inside a mini-well) on top.
Microfluidic Enhancement of Chemiluminescent Detection
This technology is a low cost, portable microfluidic platform for enhanced chemiluminescence and fluorescence detection of analytes such as drugs, pesticides and other chemicals, biological molecules or pathogens. Surface acoustic waves are employed to drive microcentifugation in a microlitre sample chamber to either enhance reagent mixing, sample preconcentration or particle concentration. The device paves the way for an attractive opportunity of a completely miniaturised platform for portable field-use microanalytical systems. Furthermore, the system can facilitate high throughput operation through ‘scale out’, via the adoption of a large number of devices in parallel. A significant advantage of such scaling out is the ease in replacing a single device in the event of a fault or when maintenance is required without necessitating complete shutdown of an entire operation. Besides enhancing performance of instrumentation across various industries, the miniaturised design and ultra high detection limits of the invention enables remote detection and analysis as well as continuous in-line industrial monitoring at quantified detection limits comparable to liquid chromatography–mass spectrometry (LC-MS) and gas chromatography–mass spectrometry GC-MS.
Bleaching-assisted Multichannel Microscopy (BAMM)
Existing imaging technologies use the colour (spectral signature) of florescent dyes to discriminate between the dyes in an image. When more than 4 dyes are used at once, it becomes very difficult to distinguish between the dyes based on their colour as they begin to overlap in their emission spectrum. This technology is a novel method called bleaching-assisted multichannel microscopy (BAMM), whereby instead of using spectral signatures of fluorescent species (ie. colours) to distinguish them in a sample/image, their photobleaching or photoswitching behaviour is used instead as the identifying property in fluorescence-multiplexed cellular imaging applications. This method can be applied either by itself or in conjunction with spectral filters and is even capable of discriminating between fluorophores with identical emission spectra. When implemented, this technology has the potential to significantly enhance the multiplexing capability of existing confocal and widefield microscopes by allowing a 2-3 times increase in the number of florescence species that can be distinguished from one another in a single image without the need for additional hardware such lasers and filters.
Nebulisation Platform Technology
The technology is a low cost, portable, nebulisation platform that can efficiently deliver next-generation drugs such as proteins, peptides and DNA to the lung, either to vaccinate against or to treat pulmonary diseases. Key features of the technology include (1) a novel chip and fluid reservoir interface that simultaneously uses both faces of the piezoelectric chip as well as use of a unique surface acoustic wave configuration (surface reflected bulk waves – SRBWs) providing both effective and efficient fluid pumping from the reservoir and nebulization - 1-2 mL/min even for fluids with high viscosity (>25cP) such as many protein/antibody drugs (2) mesh-free operation reduces fluid wastage and device blockage, (3) use of high frequency and low power ensures sample integrity is maintained and molecules of larger sizes (ie. DNA, peptides, proteins etc) are not damaged in the nebulisation process – this is particularly important when exploring application of the technology to biologics delivery. This technology has demonstrated the possibility of delivering DNA vaccines to mice, rats and sheep wherein the inhaled DNA vaccine was shown to elicit a whole body immune response against influenza that is comparable to that when delivered through injections.
A transparent, stretchable, wearable sensor
The transparent stretchable electronic devices perform accurately and repeatedly. One of the significant challenges for conformal wearable sensors and other devices worn on the body is the constant stretching and straining that they would experience as someone goes about their daily life. Polydimethylsiloxane (PDMS) is used as a substrate, which is stretchable, transparent and non-toxic. PDMS is biocompatible, and has been used in contact lenses, skin and hair products. A thin film of a metal oxide, either indium tin oxide (ITO) or zinc oxide (ZnO) or titanium dioxide (TiO2), is used as the functional part of the device. The required oxide layer is deposited on a thin layer of platinum on a silicon wafer, and then heated to required temperature to render the material function. After this heating process, the oxide is coated with PDMS. The platinum layer does not adhere well to the silicon wafer base, which means the PDMS and metal oxide layer, together with the platinum, can be easily peeled off the base. The platinum layer is removed by placing the device in chamber of gas where ions actively remove the platinum, leaving only the stretchable electronic device.
Bioprinting technology, training and design solutions provider
SE3D designs affordable desktop bioprinters ideal for training and early-stage research. Our proprietary quick-swap system facilitates ease of use and provides better mechanical control in the extrusion process over existing bioprinters. SE3D's online training platform combined with a comprehensive curriculum further facilitates rapid implementation for the end user, minimizing cost and the amount of time needed for training. Bioprinting technology has significant potential for creating bio-mimetic tissue and organ models that could improve drug development efforts and future healthcare applications such as regenerative medicine. And beyond healthcare, there are still many untapped opportunities in the biotechnology, green technology and related industries where bioprinting techniques can be applied.
Palo Alto, CA
Bioprinting of Hybrid Tissue Engineering Constructs
Stanford researchers have developed a 3D printing technology (“Hybprinter”) that can be used to form hybrid multi-material constructs incorporating a wide spectrum of materials (rigid and soft) and bioagents (such as cells and growth factors) with controlled spatial distribution across the hybrid structure. Due to its layer-by-layer manufacturing nature, Hybprinter enables the combination of cell-laden soft and hard biomaterials with a controlled spatial distribution for regenerative medicine applications. For instance, Hybprinter can be used to form connectable vascularized bone scaffolds composed of rigid, porous, osteoconductive load-bearing scaffolds and soft hydrogel vascular conduits (or channels containing soft hydrogel) with a high diffusion rate, thus eliminating the issues normally associated with surgical anastomosis of vascular grafts. The Hybprinting process also ensures high cell viability across the fabricated tissue engineering constructs.
Targeted Allergen-Specific Immunotherapy in the Skin (TASIS™)
The technology is a novel microneedle platform consisting of a targeted allergen-specific immunotherapy within the top layers of the skin (TASIS). By coating the needles on the microneedle patch in a specific way with various antigens and then applying the microneedles in a specific way, we have discovered a way to apply an immunotherapy to a historically untreatable allergy.
Microdevice for Cell Separation Based on Activation Phenotype
A microfluidic affinity separation device was developed for the detection of sepsis in critical care patients. An affinity capture method was developed to capture cells based on changes in CD64 expression in a single, simple microfluidic chip for sepsis detection. Both sepsis patient samples and a laboratory CD64+ expression model were used to validate the microfluidic assay. Flow cytometry analysis showed that the chip cell capture had a linear relationship with CD64 expression in laboratory models. The Sepsis Chip as 10% of total cells spiked into commercially available aseptic blood samples. In a proof of concept study, blood samples obtained from sepsis patients within 24 hours of diagnosis were tested on the chip to further validate its performance. On-chip CD64+ cell capture from 10 patient samples (619 ± 340 cells per chip) was significantly different from control samples (32 ± 11 cells per chip) and healthy volunteer samples (228 ± 95 cells per chip). In addition, the on-chip cell capture has a linear relationship with CD64 expression indicating our approach can be used to measure CD64 expression based on total cell capture on Sepsis Chip.
Broad Spectrum Vaccine against Influenza and Anthrax
Here, a vaccine is described which stimulates a broadly neutralizing anti-influenza response alongside an anti-anthrax response. Mice immunized with a recombinant vaccine containing multiple influenza virus antigens and attenuated edema factor (EF) from Bacillus anthracis showed enhanced cross-reactive antibody responses to influenza antigens. Additionally, mice immunized with the recombinant vaccine plus protective antigen (PA) from Bacillus anthracis showed enhanced survival to challenge with influenza virus compared to other vaccine formulations. This vaccine offers a quick and easy method of providing broad-spectrum protection against influenza and anthrax in a single formulation.
A Multipurpose Microfluidic Device for Recording Lifespan and Conducting Aging Investigations in Nematodes
Nematodes, especially C. elegans, have proven to be an effective model organism to investigate aging biology, neurodegenerative disorders, and age-related diseases. However, manual analysis of experiments related to the health and lifespan of nematodes can be highly labor-intensive, limiting experimental throughput. This new microfluidic device offers a method to remove progeny while efficiently retaining the adult worms in the device. The multi-purpose device can be used to measure lifespan curves, record health span measures, conduct drug and RNAi assays, and quantify muscle strength as a function of age. The device also provides the ability to add or remove reagents at any point, enabling novel cross-sectional and longitudinal aging experiments.
Single crystal High-frequency phase array transducer for medical diagnoses
This invention provide a transferable technology of fabricating single crystal high-frequency phase array ultrasound transducer for eye and small animal imaging. The existing technology in ultrasound phase array imaging is based on lower frequency (2-5) MHz. The fabrication process for higher frequency phase array (20 MHz above) is very difficult, especially for piezoelectric single crystal based transducer. The current invention has very large impact to industry and markets, if being commercialized, will provide more solutions for clinical diagnoses of eyes and also in micro-surgery monitoring.
East Meets West in Fighting Against Alzheimer’s Disease with Novel Dimers
Alzheimer’s disease (AD),a progressive brain disorder that severely destroys memory, has emerged as the third leading cause of death among the elderly worldwide. Although exact cause of AD remains elusive,accumulating lines of evidence have highlighted that multiple factors might contribute to progress of AD pathogenesis. Currently approved anti-AD drugs offer only limited and transient effects,but are unable to effectively slowdown or halt the disease progression. Over the past decade, with the support of grants from China and Hong Kong and collaborations with Profs. Karl Tsim, Paul Carlier,and Joel Sussman,we have developed three series of Chinese medicine-derived novel anti-AD homo- and hetero-dimers including particularly those derived from huperzine A, a unique anti-Alzheimer’s drug originally discovered from TCM. These dimers have been demonstrated to provide superior acetylcholinesterase inhibition, uncompetitive moderate N-Methyl-D-aspartate receptor antagonism, neural differentiation and remarkable neuroprotections against various neurotoxins in various in vitro and in vivo models associated with AD. Our novel dimers possess remarkable neuroprotective activities via multiple targets. More importantly,the synergism between these targets might serve as one of the most effective therapeutic strategies to modify pathological process of AD in addition to improving the cognitive functions for AD.
A novel drug candidate for cancer treatment via suppressing prostagladin E2 production
Because of the strong evidences based on the scientific and clinicopathological investigations about the etiopathological roles of the nuclear receptor peroxisome proliferator-activated receptors delta (PPAR), the development of novel anti-cancer agents which target on PPAR was strongly suggested. However, to the best of our knowledge, to date there are no clinically available drugs which were intentionally shown to inhibit the PPAR leading to the suppression of tumor growth. Thus there is a high potential value for further developing our newly patented quinoline derivative (83b1) to suppress the COX-2 and PGE2 production as a novel anti-cancer agent against cancers of gastrointestinal tract, which frequently show overexpression of COX-2 and overproduction of PGE2. The invention has been recently granted with US and China patents which were licensed to a drug company with the continuous search for sub-licensees. Moreover, the potential action of 83b1 to suppress PGE2 production will also offer another opportunity to explore it as a novel anti-inflammatory agent.
Methods and products for reducing adhesions post surgery
Researchers at the University of Adelaide have identified a novel method to treat surgical adhesions, through the use of an iron chelation and/or antioxidant agent, in both in vitro and in vivo models. In vivo studies using a sheep laminectomy model show that the antioxidant iron chelator, Deferiprone, delivered by surgical hydrogel inhibits proliferation and migration of fibroblasts. The treatment appears to reduce all key characteristics of adhesions, including the strength, thickness, extent, severity and/or vascularisation. In addition, the chosen surgical hydrogel delivery system, provided maximum release of the agent to the surgical site within 48 hours. This is consistent with the critical period for blocking adhesion formation.
Arsenol - an oral formulation of arsenal
Arsenol is a drug developed entirely in Hong Kong, having a bioactivity similar to the IV formulation, but has lower peak plasma arsenic concentrations, hence a lower cardiac toxicity. Arsenol is also convenient and safe for outpatients, rendering long-term therapy feasible and a massive saving in hospitalization cost.
Daidzein and other analogs as agents for purging HIV reservoir
This new discovery has a potential to develop into a treatment for eradication of HIV thoroughly in combination with highly active anti-retroviral therapy (HAART). In HIV research, proviral latency in specific long-lived cell types is the basis for the concept of one or more viral reservoirs, referring to locations (cell types or tissues) characterized by persistence of latent virus. Specifically, the presence of replication-competent HIV in resting CD4-positive T cells, allows this virus to persist for years without evolving despite prolonged exposure to antiretroviral drugs. This latent HIV reservoir explains the inability of antiretroviral treatment to cure HIV infection. The ability of HIV-1 to establish a latent infection presents a barrier to curing HIV. As special agents, Daidzein and its analogs can safely kick-start production of the dormant virus in patients, so that it might be detected and attacked more easily by the immune system. A combination treatment with Daidzein or its analogs and HAART may lead to complete clearance of HIV infection.
OPTIClear - a tissue clearing agent
OPTIClear is developed based on the novel concept of using three key components: (1) A lipid-soluble, membrane refractive index (RI) adjusting agent: selectively adjusts the RI of the lipid-rich compartments of the tissue (2) A water-soluble, cytoplasmic refractive index adjusting agent: selectively adjusts the RI of the aqueous compartments of the tissue (3) A physical homogenizing agent: facilitate true homogenization of the above two agents and the tissue components to achieve better optical homogeneity. Light is bent as it passes through the boundary of different transparent media due to their differences in RI, leading to a perceived boundary. Therefore, one should adjust the RI of each medium to a defined value such that they are equal to each other to minimize the bending of light paths, hence no perceived boundary can be seen and the tissue would become transparent.
Quantum probe for hyperpolarising MRI contrast agents
The quantum hyperpolarisation system relies on a controlled quantum probe to hyperpolarise external molecular nuclear spins. The magnetic spin induced in the quantum probe using a controlled laser is transferred to the external molecule through a cross-relaxation process. From a deep understanding of the timing of the cross-relaxation process, the spin of the quantum probe is maintained at the desired state to ensure continuous transfer of the spin state to the external molecule. Exposure of MRI contrast agents, such as carbon-13, to the quantum hyperpolarisation system tuned to the specific nuclei results in highly polarised contrast agents with relatively short preparation time. Once hyperpolarised, the contrast agent can be introduced into the patient to improve MRI contrasts and further enables metabolic imaging. Due to the short lifetime of such contrast agents in maintaining their hyperpolarised state, hyperpolarisation needs to be performed onsite. The technology would simplify the requirements to enable effective hyperpolarisation and would significantly impact the MRI market, valued at US$5.6b in 2016, as it would improve existing MRI capabilities by a few orders of magnitude. Easier access to improved MRI capabilities would significantly improve medical care and diagnosis, particularly for emerging economies reliant on older MRI machines.
Antimicrobial Agents for Combating Multiple Drug Resistant Bacteria
Infections caused by multi-drug resistant (MDR) bacteria have been named as one of the most urgent health threats due to the lack of effective and biocompatible drugs. Despite the fact that many bacteria have acquired antibiotic resistance, the pipeline for the development of new antimicrobials remains empty. This is attributed to the mode of action of conventional antibiotics; which act on specific intracellular targets. In light of this pressing issue, a new class of star-shaped peptide particles, termed ‘structurally nanoengineered antimicrobial peptide polymers' (SNAPPs), have recently been developed and shown to possess high efficacy towards Gram-negative, Gram-positive and MDR bacteria (i.e., ESKAPE and colistin-resistant). Even after 600 generations of growth in the presence of SNAPPs, no resistance acquisition by MDR A.baumannii to SNAPPs was observed. The high efficacy of SNAPPs towards MDR A.baumannii infections has also been shown in-vivo, and after post treatment, all in-vivo models survived, with no signs of animal distress. Recently, SNAPPs have also shown to be useful as adjuvants with conventional on the market drugs, allowing these conventional drugs to gain new efficacy against Gram negative bacteria and MDR pathogens.
Meshless Clog-Free Battery-Run Pocket-Size Ultrasonic Nebulizer
Drugs designed to treat lung diseases require optimal droplet (aerosol) size (2-6µm) for efficient delivery. Current commercial nebulizers utilize piezoelectric disk with a mesh (array of micron-size holes) to produce aerosols of uncontrolled broad size distributions, resulting in inefficient use of expensive drugs. They often clog due to the mesh and overheat due to high drive power. The innovation and potential applications of the mesh-less delivery device reported here were highlighted in the prestigious TECHNOLOGY, 2, 75, 2014 . The key element of this new nebulizer, the patented centimeter-size nozzle, consists of drive and resonator sections batch-fabricated in a silicon wafer using MEMS technology (Fig.2B of ). (See working principle in Value Proposition.) For the drive frequency of 1-3 MHz, the droplet sizes measured 2.5-6.0µm in agreement with the theoretical predictions. Proto-type pocket-size nebulizers (see video link) have been constructed to deliver antidotes for detoxification of massive cyanide poisoning (sponsors NIH/Army) and common pulmonary drugs. These proto-type units have produced droplets of optimal size at typical throughput of 0.5 mL/min and very low drive power (0.3 Watt). The new nebulizer has imminent potential to fulfill current unmet needs.
Visitube: Video-Guided Chest Tube Insertion System
Dr. Robert Cameron has designed a novel trocar system that supports visual monitoring of chest tube placement. Chest tubes are placed into the pleural space of patients who have an excess of air and/or fluid that is collapsing a lung. Traditional chest tube placement through an incision often causes excessive pain and may result in poor tube position as well as organ damage, as there is no method to assess its location. The new device, capitalizing on existing medical video technology, contains a video source that would provide real-time information on the anatomical position of the trocar and allow steerable placement of the chest tube. Once inserted, an expandable balloon increases the size of the trochar portion of the device, thereby accommodating many chest tube sizes. The precise placement would require only a localized injection of anesthesia.
Real time cancer cell detector for clean margins in primary breast cancer surgery
The technology quantifies the microenvironment pH with an optical fibre sensor. Acidic pH has been established to be mechanistically linked with the persistence and growth of all cancer types. The sensor utilises a fluorophore doped polymer coating, deposited on the tip of a 200 μm diameter optical fibre, with the pH measured by simply placing the tip of the probe in contact with the tissue surface for only a few seconds. We have already secured clinical trial data which demonstrates that the sensor is capable of differentiating between cancerous and normal tissues with a resolution of 5-10 cells, equivalent to classical diagnostic pathology, reducing the need for repeat surgery.
Novel formulation for treatment of bacterial biofilms
Researchers at the University of Adelaide have developed a novel combination product, targeting the bacterial iron metabolism, to slow the growth, survival and pathogenesis of bacterial infection, in particular targeting Methicillin resistant Staphylococcus Aureus (MRSA) and Staphylococcus Aureus (S. Aureus). The product is a combination of 2 molecules: Deferiprone – an iron chelator which takes up the bacteria’s natural food source, causing starvation; and Gallium-Protoporphyrin – a haem analogue, which works to inhibit the bacteria’s essential cellular pathways in combination, these two molecules (collectively “Def-GaPP”) have strong synergistic antimicrobial properties to kill multidrug resistant bacteria, making them an ideal pair for improved wound healing. We have compelling in vitro and in vivo data (large animal model) demonstrating safety and efficacy of this combination product. We are now moving to Phase 1 human clinical trials.
Circulatory Cells as Carriers for Photo-Activated Bioregulators
This invention allows targeted therapy of damaged or diseased tissues using small molecule bioregulatory molecules (SBRMs) like nitric oxide (NO), carbon monoxide (CO) and carbon disulfide (CS2). These therapeutic compounds are metabolized rapidly by the body if they are not encapsulated and released at the target tissue. To control dosage and release, light-activated mechanisms are employed to release these therapeutic bioregulators (PhotoSBRMs). Unfortunately, the short, high energy light required by PhotoSBRMs is scattered by tissue limiting the activation depth and making them impractical for human use. NIR light scatters less and penetrates deep into tissues making it a better activator for treatments. To use NIR light, an upconverter is employed to convert longer wavelength light to shorter wavelength and activate PhotoSBRMs. In order to target damaged or diseased tissues, cells can be used as carriers. Immune cells target sites of inflammation and easily internalize the encapsulated PhotoSBRMs to transport them. In other cases, blood cells or cells engineered to target an antigen can be used. Once the cells reach the target, NIR light can be applied to release the nitric oxide at the target location. This versatile approach could be used to help treat solid tumors or even shin splints.
Highly Stretchable & Flexible Electronic Sensors
Typical electronics do not stretch but these do and they maintain their signal integrity when stretched. The device can be used as a stretchable electronic interconnect or as a sensor. The device is formed from thin, twisted conductive tubules that are filled with a liquid metal alloy conductor. The liquid metal alloy is non-toxic making it safe for wearable applications. The tubules can be fabricated using a simple roller coating process but this process can be scaled using standard tubing manufacturing processes. The mechanical performance and electronic sensitivity of these devices is tuned by varying the number of twists in the tubules and the pre-tensioning. They can be used to sensors strain, contact force, rotation, and tactile sensing even while being stretched (>600% strain. The sensors are also highly flexible, durable, and reliable (over 5,000 cycles). These features allow them to conform curved or variable surfaces, including the human body and collect reliable measurements during movements. This information can be used to measure and record complex human actions for analysis or to remotely control robots. This will lead to new applications in areas including wearable computing, healthcare, surgical robotics, field robotics, manufacturing, entertainment, and rehabilitation.
Alzheimer’s disease pathophysiology following brain injury in sleep deprivation is reduced by co-administration of TiO2 nanowired delivery of AβP and Tau antibodies together with cerebrolysin
Military personnel are often prone to stress of sleep deprivation (SD) resulting in blood-brain barrier (BBB) disruption and leakage of serum components in the brain. This would trigger a variety of reaction within the cerebral compartments that may trigger Alzheimer’s disease (AD) like pathophysiology including amyloid beta peptide (AβP) deposition from plasma and Tau protein phosphorylation. Additional traumatic brain injury (TBI) may further aggravate AD pathology. In this innovation we used TiO2 nanowired delivery through intracerebroventricular (i.c.v.) administration of antibodies to AβP (1:20 50 ng in 100 µl, i.c.v.) and Tau (1:20, 10 µg in 100 µl) together with cerebrolysin (5 mg/kg, i.v.)-a multimodal drug after 4 and 8 h of TBI induced by an impact of 0.224 N on the right parietal skull following 48 h SD in rats. SD was induced by an inverted flowerpot model in rats. This combination of nanomedicine significantly reduces AβP and Tau concentration in the brain and prevented BBB leakage and brain pathology in SD with TBI at 48 h survival. These results may open novel therapeutic strategy to treat military personnel for such conditions effectively.
An innovative 3D tissue matrix scaffold system for tumor modeling
The mammalian extracellular matrix (ECM) is comprised of a labyrinth of interconnected architecture that provides mechanical support and optimal tissue microenvironment for cell survival, growth, signal transduction and interactions. The currently available scaffold and planar tissue culture models using synthetic polymers or a single component of ECM do not resemble this native living microenvironment. Therapeutic studies and preclinical applications based on these methods have failed to provide consistent data and acceptable efficacies. In addition, post-degradation toxicity caused by the polymeric scaffolds disrupts cell-to-cell signaling, leading to defects in secretion of biomolecules/enzymes, rejection of scaffold graft, cell death and severe side effects. These factors necessitate a “next-generation” of scaffold system that resembles native ECM for reliable scientific research, drug testing and tissue regeneration studies.In order to address the above problems, WSU has developed Tissue Matrix Scaffold (TMS), a versatile 3D matrix, which is an intermediate platform between 2D culture models and more complex and expensive in vivo models. The decellularized TMS retains the structural and compositional nature of ECM, making it well suited for both scientific research and clinical applications.
Pathophysiology of brain blast injury is reduced by co-administration of TiO2 nanowired delivery of cerebrolysin with neprilysin and antibodies of amyloid beta peptide
Spinal cord injury (SCI) is highly prevalent in military personnel resulting them for lifetime paralysis. In this innovation we used TiO2 nanowired delivery of cerebrolysin (250 µl over 30 sec) with antibodies to neuronal nitric oxide synthase (nNOS, 1:20 50 µg/30 µl) in combination with mesenchymal stem cells (MSCs, 1 million cells) repeatedly over the traumatized spinal cord starting from 3 h after injury hourly application up to 8 h and found excellent recovery of functional parameters as measured by spinal cord evoked potentials (SCEP) and behavioural dysfunction 24 h primary injury. Also, cord pathology is significantly reduced at 24 h SCI. These results suggests that when our soldiers are inflicted with SCI topical application with these agents can reduce the spinal cord damage and improve behavioral outcome up to 24 h while they are transported to specialized facilities for further treatment option.