Capturing tears to detect exosomes, nanometer-sized vesicles found in bodily secretions, have the potential for being diagnostic cancer biomarkers.
Scientists from the Terasaki Institute for Biomedical Innovation (TIBI) have developed a contact lens that can capture and detect exosomes, nanometer-sized vesicles found in bodily secretions which have the potential for being diagnostic cancer biomarkers. The lens was designed with microchambers bound to antibodies that can capture exosomes found in tears. This antibody- conjugated signaling microchamber contact lens (ACSM-CL) can be stained for detection with nanoparticle-tagged specific antibodies for selective visualization. This offers a potential platform for cancer pre-screening and a supportive diagnostic tool that is easy, rapid, sensitive, cost-effective, and non-invasive.
Exosomes are formed within most cells and secreted into many bodily fluids, such as plasma, saliva, urine, and tears. Once thought to be the dumping grounds for unwanted materials from their cells of origin, it is now known that exosomes can transport different biomolecules between cells. It has also been shown that there is a wealth of surface proteins on exosomes – some that are common to all exosomes and others that are increased in response to cancer, viral infections, or injury. In addition, exosomes derived from tumors can strongly influence tumor regulation, progression, and metastasis.
Because of these capabilities, there has been much interest in using exosomes for cancer diagnosis and prognosis/treatment prediction. However, this has been hampered by the difficulty in isolating exosomes in sufficient quantity and purity for this purpose. Current methods involve tedious and time-consuming ultracentrifuge and density gradients, lasting at least ten hours to complete. Further difficulties are posed in detection of the isolated exosomes; commonly used methods require expensive and space-consuming equipment.
The TIBI team has leveraged their expertise in contact lens biosensor design and fabrication to eliminate the need for these isolation methods by devising their ACSM-CL for capturing exosomes from tears, an optimum and cleaner source of exosomes than blood, urine, and saliva.
They also facilitated and optimized the preparation of their ACSM-CL by the use of alternative approaches. When fabricating the microchambers for their lens, the team used a direct laser cutting and engraving approach rather than conventional cast molding for structural retention of both the chambers and the lens.
In addition, the team introduced a method that chemically modified the microchamber surfaces to activate them for antibody binding. This method was used in place of standard approaches, in which metallic or nanocarbon materials must be used in expensive clean-room settings.
The team then optimized procedures for binding a capture antibody to the ACSM-CL microchambers and a different (positive control) detection antibody onto gold nanoparticles that can be visualized spectroscopically. Both these antibodies are specific for two different surface markers found on all exosomes.
In an initial validation experiment, the ACSM-CL was tested against exosomes secreted into supernatants from ten different tissue and cancer cell lines. The ability to capture and detect exosomes was validated by the spectroscopic shifts observed in all the test samples, in comparison with the negative controls. Similar results were obtained when the ACSM-CL was tested against ten different tear samples collected from volunteers.
In final experiments, exosomes in supernatants collected from three different cell lines with different surface marker expressions were tested against the ACSM-CL, along with different combinations of marker-specific detection antibodies. The resultant patterns of detection and non-detection of exosomes from the three different cell lines were as expected, thus validating the ACSM-CL’s ability to accurately capture and detect exosomes with different surface markers.
“Exosomes are a rich source of markers and biomolecules which can be targeted for several biomedical applications,” said Ali Khademhosseini, Ph.D., TIBI’s Director and CEO. “The methodology that our team has developed greatly facilitates our ability to tap into this source.”
Additional authors are: Shaopei Li, Yangzhi Zhu, Reihaneh Haghniaz, Satoru Kawakita, Shenghan Guan, Jianjun Chen, Kalpana Mandal, Juchen Guo, Heemin Kang, Wujin Sun, Han-Jun Kim, Vadim Jucaud, Mehmet R. Dokmeci, Pete Kollbaum, Chi Hwan Lee, and Ali Khademhosseini.
Flexible implanted electronics are a step closer toward clinical applications, could treat spinal cord injury and Parkinson’s disease.
A recent breakthrough technology developed by a research team from Griffith University and UNSW Sydney was pioneered by Dr Tuan-Khoa Nguyen, Professor Nam-Trung Nguyen and Dr Hoang-Phuong Phan (currently a senior lecturer at the University of New South Wales) from Griffith University’s Queensland Micro and Nanotechnology Centre (QMNC) using in-house silicon carbide technology as a new platform for long-term electronic biotissue interfaces.
The project was hosted by the QMNC, which houses a part of the Queensland node of the Australian National Nanofabrication Facility (ANFF-Q).
ANFF-Q is a company established under the National Collaborative Research Infrastructure Strategy to provide nano- and microfabrication facilities for Australia’s researchers.
The QMNC offers unique capabilities for the development and characterisation of wide band gap material, a class of semiconductors that have electronic properties lying between non-conducing materials such as glass and semi-conducting materials such as silicon used for computer chips.
These properties allow devices made of these materials to operate at extreme conditions such as high voltage, high temperature, and corrosive environments.
The QMNC and ANFF-Q provided this project with silicon carbide materials, the scalable manufacturing capability, and advanced characterisation facilities for robust micro/nanobioelectronic devices.
“Implantable and flexible devices have enormous potential to treat chronic diseases such as Parkinson’s disease and injuries to the spinal cord,” Dr. Tuan-Khoa Nguyen says.
“These devices allow for direct diagnosis of disorders in internal organs and provide suitable therapies and treatments.
“For instance, such devices can offer electrical stimulations to targeted nerves to regulate abnormal impulses and restore body functions.”
Because of direct contact requirement with biofluids, maintaining their long-term operation when implanted is a daunting challenge.
The research team developed a robust and functional material system that could break through this bottleneck.
“The system consists of silicon carbide nanomembranes as the contact surface and silicon dioxide as the protective encapsulation, showing unrivalled stability and maintaining its functionality in biofluids,” Nguyen says.
“For the first time, our team has successfully developed a robust implantable electronic system with an expected duration of a few decades.”
The researchers demonstrated multiple modalities of impedance and temperature sensors, and neural stimulators together with effective peripheral nerve stimulation in animal models.
Corresponding author Dr Phan says implanted devices such as cardiac pace markers and deep brain stimulators had powerful capabilities for timely treatment of several chronical diseases.
"Traditional implants are bulky and have a different mechanical stiffness from human tissues that poses potential risks to patients. The development of mechanically soft but chemically strong electronic devices is the key solution to this long-standing problem,” Phan says.
The concept of the silicon carbide flexible electronics provides promising avenues for neuroscience and neural stimulation therapies, which could offer live-saving treatments for chronic neurological diseases and stimulate patient recovery.
“To make this platform a reality, we are fortunate to have a strong multidisciplinary research team from Griffith University, UNSW, University of Queensland, Japan Science and Technology Agency (JST) - ERATO, with each bringing their expertise in material science, mechanical/electrical engineering, and biomedical engineering,” Phan says.
Münster surgeons use new operating method for the first time anywhere in the world.
It’s a great success for robotic microsurgery not only in Münster but worldwide – both for medicine and for science: a team led by scientists Dr. Maximilian Kückelhaus and Prof. Tobias Hirsch from the Centre for Musculoskeletal Medicine at the University of Münster has carried out the first completely robot-supported microsurgical operations on humans. The physicians used an innovative operating method in which a new type of operations robot, designed especially for microsurgery, is networked with a robotic microscope. This approach makes it possible for the operating surgeon to be completely taken out of the operating area. The use of robots for clinical research is undertaken in collaboration with Münster University Hospital and Hornheide Specialist Clinic.
The experts have been using this method for a good two months. So far, five operations have been successfully performed, with many more set to follow. “This new method for operations enables us to work with a much higher degree of delicacy and precision than is possible with conventional operating techniques,” says Maximilian Kückelhaus. “As a result, less tissue is destroyed and patients recover faster.” The specialists use the method for example on patients with breast cancer who need complex breast reconstructions, or after accidents in which patients need tissue transplants. With the aid of the robot and the robotic microscope, the microsurgeons can for example join up again the finest anatomical structures such as blood vessels, nerves or lymphatic vessels, which often have a diameter of only 0.3 millimeters.
During the operation, the robot – the so-called Symani Surgical System – adopts human hand movements via an electromagnetic field and joysticks. The robot carries out the operating surgeon’s movements, reduced in size by up to 20 times, via tiny instruments and, in doing so, completely eliminates any shaking present in (human) hands. A robotic microscope is connected to the operation robot, and this microscope shows the area being operated on via a so-called 3D Augmented Reality Headset with two high-resolution monitors. This headset contains a binoculars which are able to combine the real world with virtual information. In this way, the surgeon’s head movements can be recorded and transferred to the robot, making even complicated viewing angles possible on the area being operated on. In addition, the operating surgeon can access a variety of menus and perform functions with the robot without using his or her hands.
The new technology also has the advantage that operating surgeons can adopt a relaxed posture – whereas they otherwise have to perform operations in a strenuous posture over a period of several hours. “As we can now operate on patients in a remote fashion, we have much better ergonomics,” says Tobias Hirsch, who holds the Chair of Plastic Surgery at Münster University. “This in turn protects us from fatigue, and that means that our concentration can be maintained over a period of many hours. In initial studies involving the systems, before they were used in operations, we were already able to confirm the positive effects on the quality of operations and on ergonomics.” During training with students and established microsurgeons, the physicians were able to demonstrate that, while using the robotic system, the learning curve, the handling of the instruments, and the ergonomics all demonstrated an improvement over conventional operating techniques.
In the coming weeks and months, Maximilian Kückelhaus and Tobias Hirsch will be performing further operations and, in the process, collect data that they will be evaluating in scientific studies. Important issues to be addressed are, in particular, improvements to the quality of operations and to ergonomics. “Our hope is that with this new method we can not only perform operations with a greater degree of precision and safety – but also, in the case of the tiniest structures, go beyond limits imposed by the human body. Not having to be at the operating table can also mean that one day the operating surgeon will no longer have to be physically present. An expert might be able to perform special operations at any one of several locations – without having to travel and be there in person,” says Maximilian Kückelhaus, looking into the future.
Funding For the development of, and the clinical trials for, this new method of treatment, Maximilian Kückelhaus received funding from the European Union initiative entitled “Recovery Assistance for Cohesion and the Territories of Europe”.
GROB Systems will hold live 5-axis machining of challenging medical, aerospace, and mold parts at IMTS.
GROB Systems Inc., a global leader in the development of manufacturing systems and machine tools, announced its schedule for demonstrating a range of 5-axis machining applications on its compact G350 Generation 2 Universal Machining Center at IMTS (International Manufacturing Technology Show) Booth #431400 (shared booth with YG-1 Tool Co.) at McCormick Place in Chicago, IL from September 12-17 this year. Attendees can see how GROB meets and exceeds the demands of aerospace, medical and die/ mold machining, and GROB personnel will be on-hand to answer specific customer application questions.
Here are the details on the three machining applications:
GROB machining centers are made in the U.S.A. at the GROB Systems 400,000 sq. ft. full production facility in Ohio and can include advanced automation solutions for dramatically increased productivity. The GROB G350 on display at the show will include a dynamic rotary table with a 200 rpm B-axis with infinite rotation, and a maximum rotation of 360° in the A-axis. This G350 Generation 2 machining center is equipped with a Siemens 840D sl control, 16k rpm spindle, 117-tool holding capacity, and a HSK-A63 tool interface.
Learn how to follow a blueprint in order to implement automation.
About the presentation Successful implementation of manufacturing automation projects starts with a clear understanding of desired goals, objectives, requirements, and potential short-term and long-term challenges. As with any significant investment, including automation, conducting discovery is critical to defining the scope of a project and identifying solution(s) that’ll be within budget, produced, and installed on schedule, and have the greatest return on investment (ROI). Automation solutions are best when scalable and manageable and have defined operator functions, part processing requirements, and operating environments. Purchasing an automation system with monitoring and feedback functionality will support long-term goals and continuous improvement efforts.
Dave Walton, director of engineering at Makino, has the expertise to help you make the discovery process easier and less daunting. Join him for a walkthrough of an automation blueprint developed over decades of successful implementations. Learn more about essential elements of automation and available tools and solutions.
Meet your presenter Dave Walton is the director of engineering operations at Makino Inc., Mason, Ohio. He’s been with Makino for 25 years, working in the areas of factory automation and integrating automation with the Makino machine platform, and later managing the engineering group responsible for executing the Makino automation programs. Walton’s total experience in factory automation spans more than 40 years, including stints with General Motors (GM) and GE Aviation prior to his current employment by Makino.
About the company The Makino commitment to customers starts with work in metal-cutting and manufacturing technology with horizontal machining centers, vertical machining centers, wire and ram EDM, and graphite machining centers. Helping customers make what matters also means Makino is both a software company and an engineering services company. A service company and a financing company. A turnkey engineering company and an integration services company. An automation systems company and a machine tool supply company. A training company and a process technology company. Makino is the one company you need to machine parts more accurately, productively, and at a lower cost per part. The partner you need to build and sustain a metal-cutting business that thrives by making the best for the customers that matter most.