Invenios, Inc. The bio-fluid printer and our key advisors are closely connected to Invenios, which was founded by Ray Karam in October of 2002. Invenios’ mission is to bring micromanufacturing to the third dimension. Arrays of products, process technologies and services from Invenios have been designed in order to allow for the next generation of integrated nanosystem and microsystem products and technologies. Invenios is a manufacturer of production equipment and custom 3D micromachines that help emerging manufacturing companies reduce prototype, production, and packaging costs for a range of microsystem manufacturing applications. Our key advisors include Ken Richards, Ray Karam, and George Roussos. Ray Karam is the president and CEO of Invenios who is an accomplished entrepreneur in the materials and precision engineering arenas. Ken Richards is vice president and in charge or finance for Invenios. He has 25 years of experience in the corporate and investment banking. Including George Roussos, the director of engineering for Invenios, these three advisors have assisted in supplementing, focusing, and informing our team for this project. Jim Harber, PhD and ChingHua Wang, MD, PhD have also been an incredible source of assistance throughout the process of completing this project. Bio-fluid Printer Invenios’ bio-fluid printer is essentially a high speed, highly accurate device capable of dispensing small volumes in the pL range. The product is produced as cartridges (figure 1) approximately the size of a microscope slide. Each cartridge can contain up to 128 print heads. Each print head is self contained and piezo driven. Figure 1: Invenios’ bio-fluid printer cartridge The extremely small size of the printer heads allow the bio-fluid printer to eject droplets between 30-1000pL. The piezo system that is utilized in the printer heads is what allows for speeds up to 10,000 droplets per second in a flow through system. By using the print heads along with another Invenios product, their nanopositioning motion control technology, the bio-fluid printer is capable of dispensing fluids at resolutions up to 600dpi very accurately. Figure 2: Diagram of a typical printer head The technology used in Invenios’ printer heads is very similar to the technology that has been used in standard inkjet printers since the 1980’s, except Invenios’ printer heads are smaller and have a primary structure entirely made of glass. Each print head consists of a piezo that is attached to the side of the printer head along the coverplate. When the piezo is electrically charged it will cause the piezo to alter its shape, essentially bending away from the cavity, pulling the coverplate with it. By pulling the coverplate away from the cavity, the charged piezo creates a small vacuum in the cavity and as a result fluid is drawn into the cavity from the input at the top of the printer head (figure 2). The fluid is pull mainly from the input and not the nozzle due to the capillary effect that increases the required amount of force necessary to moving the fluid in the nozzle tip into the cavity compared to the input. When the piezo is no longer charged, it will return back to its rest state along with the coverplate that it is attached to. Because there is now more fluid in the cavity, the piezo put pressure on the fluid within the cavity. The piezo is charged intermittently very quickly and as a result creates essentially waves within the cavity. Theses waves result in the ejection of fluid from the print head at varying speeds depending on the speed that the piezo is being intermittently charged. One of the key factors that makes Invenios’ bio-fluid printer so unique is that the cartridges are made entirely of glass. Glass has several unique properties that make it ideal for bio-fluidics. The benefits include glass’ capability to act as a electrical insulator and its ability to remain chemically stable. This allows Invenios’ bio-printer to be used with a wide variety of fluids if necessary for a particular application, such as oil-based, extreme solvent-based, UV curable, extreme pH level, corrosive, and hot melt fluids. The glass used by Invenios is also ideal due to its ability to retain structural rigidity even when sustaining high temperatures up to 400ºC. But more importantly for bio-fluids, the technology used in Invenios’ printers allow for the ejection of the fluids without needing the fluid to come into contact with anything but glass and the fluid is also not exposed to any temperature stress during the process. This makes the printer safe for dispensing various bio-fluids such as serums, proteins, enzymes, vaccines, or even stem cells. Because of the non-reactive nature of the bio-fluid printer, it is ideal for any type of application that may need FDA approval. Direct-Write Laser Patterning Process Not only is glass an ideal medium for bio-fluidics, but it is also an essential component that allows Invenios’ direct-write laser patterning process to function in order to create the nano scale channels in glass for the bio-fluid printer heads. The term “direct write” refers to “any technique or process capable of depositing, dispensing, or processing different types of materials over various surfaces following a present pattern or layout” (Alberto Pique). The laser patterning process takes advantage of very unique characteristics that are inherent in photo-structurable glass ceramics. When this type of glass is exposed to UV laser energy density greater than a critical fluence, a photo-chemical reaction takes place that will create a density of nanocrystals within the criticall-expised volumes (figure 3). Figure 3: UV exposed photo-structurable glass. The amount of nanocrystals that forms is directly proportional to the amount of fluence that is applied to the glass. Sub-micron features within the glass can be created by controlling the aperture of the UV laser optics and depth of focus. A larger depth of focus can be used in order to create larger densities of nanocrystrals, resulting in a larger canal formed for the bio-fluid printer head. Each critically exposed volume can be extended to form a specific path by utilizing successive pulses from the laser. The path can be precisely controlled by using a computer controlled multi-axis positioning system. By using this technique and altering the characteristics of the laser, complex 3D volumes of nanocrystals can be formed. By using Invenios’ thermal treatment protocol, the nanocrystals can be grown to form large crystalline structures. The thermal treatment protocol and the fluence levels that were applied to the glass will cause the “ceramicized” material to change color. The material will transition from transparent though yellow, orange, red, brown, and finally black. This characteristic allows for the creation of embedded masks with sub-micron features. When the glass is subjected to a mild etchant, the areas of the glass that were critically exposed by the UV laser will etch faster than the unexposed regions by an etch contrast ratio that is defined by a non-linear function of the exposure. Etch rate contrasts of 25:1 have been observed (F.E. Livingston). This suggests that there is a very small range that is undesirable because it is not critically exposed or unaffected by the laser. As a result, when etching the critically exposed volume can be removed, but small amounts of non-exposed volumes at the boundary will be removed as well. Because the amount is so minor, the technique is still capable of creating the sub-micron features that are required for the bio-fluid printer heads. After the etching processes a second UV exposure and baking step can take place. This additional step of thermal treatment and UV exposure is used in order to convert the glass into the full ceramic state. Nano Positioning The bio-fluid printer cartridges are capable of ejecting the droplets with consistent velocity and direction. The bio-fluid cartridges can also eject droplets as small as 30pL, but these impressive capabilities would all be useless if there was not a mechanism in place to have the cartridges accurately positioned over their desired targets. To do this, Invenios implemented another technology that they have ownership of, their nanopositioning motion control technology. The combination of the small nozzle distances between the printer heads and Invenios’ nanopositioning motion control technology allows the bio-fluid printer to dispense fluids at resolutions up to 600dpi. The precision linear and rotary stages that Invenios’ owns is a scalable precision ballscrew stage that is capable of the precise nanopositioning that is required for the accurate dispensing of bio-fluids with their bio-fluid printer. Invenios’ has a nano series of the precision linear and rotary stages that allows them to achieve sub-micron out-of-plane motion at intervals as small as 0.05um over 10mm. It is also capable of precision linear resolution and repeatability of 1nm using a dual-loop feedback system. Alberto Pique, Douglas B. Chrisey, “Direct-Write Technologies for Rapid Prototyping Applications: Sensors, Electronics and Integrated Power Sources,” Academic Press, 2002, pg. XIX F. E. Livingston and H. Helvajian, " True 3D Volumetric Patterning of Photostructurable Glass using UV Laser Irradiation and Variable Exposure Processing: Fabrication of Meso-scale Devices," SPIE Proc. Vol. 4830 (2003) pg. 189-195. Invenios, Inc, “Micro Applications, Nano Positioning, and Company,” www.invenios.com