June 28, 2022 - Scientists at the University of Houston have developed a novel method of 3D printing biosensors that could one day be implanted in human hosts. Using multiphoton lithography (MPL), the team polymerised resins containing organic semiconductor materials layer by layer to form tiny, biocompatible circuit boards. So far, the researchers have used the new process to create highly accurate glucose sensors. With further development, they believe it could pave the way for the production of a new generation of bioelectronic devices.

The new 3D bioprinting process introduces a homogeneous and transparent photosensitive resin doped with organic semiconductor (OS) materials to fabricate a variety of three-dimensional OS composite microstructures (OSCM)," the researchers said in their paper. Our] results demonstrate the great potential of these devices in a wide range of applications from flexible bioelectronics to nanoelectronics and organ-on-a-chip devices."

△ The researchers' initial 3D printed microstructure. Image from the University of Houston.

Bringing conductive implants to life

In their paper, the researchers identify MPL as the "most advanced" direct laser writing (DLW) 3D printing technology because of its material versatility and the high level of precision it can achieve (down to 15 nm resolution). As such, the Houston team believes that this technology is ideal for producing the types of nanoelectronic devices that have been the focus of research over the past few years. However, the feasibility of 3D printing such biological implants is still limited by the low conductivity of the raw material. According to the scientists, this is due to the fact that bioelectronic prototypes are usually made from carbon nanotubes or graphene, and as such they have inorganic properties - "it is difficult to disperse them uniformly in the resin" and "there is no significant phase separation". To get around these drawbacks, the Houston researchers have developed an exclusive MPL resin consisting of PEGA polymers loaded with DMSO, PEDOT:PSS organic semiconductors, laminin and glucose oxidase, which can be precisely 3D printed into mini bio-circuits with homogeneous properties.

△The team's organic electronics 3D printing workflow. Image from the University of Houston.

3D printing cell-compatible PCBs   

Initially, the researchers used their material to produce multiple microelectronic devices, including a printed circuit board (PCB) featuring an array of miniature capacitors. Once they had proven the effectiveness of their technique, the team began experimenting with laminin, a glycoprotein found in the membranes of different animal tissues that facilitates cell attachment, signalling and migration. After loading their resin with the protein, the team 3D printed it into further complex microstructures, which were then incubated in mouse tissue for 48 hours. The scientists noted that their cells showed "enhanced viability" compared to samples that were not loaded with protein, while retaining the ability to promote attachment and proliferation.

After determining the biocompatibility of their implant, the researchers sought to assess the electrochemical properties of the device. Tests at the biologically relevant frequency of 1kHz showed that the electrical impedance of the team's PCBs decreased at all frequencies (1 to 105Hz) as the diameter of the microelectrodes increased, with results consistent with those previously reported. Finally, to demonstrate the application potential of their method, the scientists used it to produce a new type of biosensor capable of deploying electrical currents to detect glucose levels with high stability and accuracy. Given that the device is 10 times more sensitive than current monitors, the team says their resin could now help accelerate progress towards electronic implants in humans.

In their paper, the researchers conclude, "We anticipate that the proposed MPL-compatible OS composite resin will pave the way for the production of flexible, bioactive and conductive microstructures that are expected to be put to use in various applications in emerging fields such as flexible bioelectronics/biosensors, nanoelectronics, organs-on-a-chip and immune cell therapy.

△ A set of 3D printed microstructures infused with laminin. Image from the University of Houston

Advancing the development of controlled implants

While the idea of a controllable implant may sound sci-fi, the Houston team's project is not the first in terms of bringing this vision to life through 3D printing technology. In the past, Renishaw conducted a study with Herantis Pharma that saw it 3D print a neuroperfusion drug delivery device designed to treat Parkinson's disease.

Similarly, scientists at the University of Sheffield, St Petersburg State University and Dresden University of Technology have previously developed a 3D printed neural implant for the treatment of neurological injuries. The device, at least in theory, combines biology and electronics to connect the brain to a computer, thus giving doctors the ability to address neurological disorders.

Similarly, in another experimental use case, Joshua Uzarski of the CCDC Soldier Centre told the 3D printing industry last year that the US Army is currently working on cyberpunk-style biosensors. These devices, which are still in the very early stages of development, could be used to physiologically track troops while also providing them with enhanced awareness of potential situational threats on the battlefield.

The researchers' findings are presented in their paper entitled "Multiphoton Lithography of OrganicSemiconductor Devices for 3D Printing of Flexible Electronic Circuits, Biosensors and Bioelectronics/Multiphoton Lithography of OrganicSemiconductor Devices for 3D Printing of Flexible Electronic Circuits, Biosensors and Bioelectronics Electronic Circuits, Biosensors, and Bioelectronics". The study was co-authored by Omid Dadras-Toussi, Milad Khorrami, Anto Sam Crosslee Louis Sam Titus, Sheereen Majd, Chandra Mohan and Mohammad Reza Abidian.

Link to related paper: https://onlinelibrary.wiley.com/doi/10.1002/adma.202200512