Category: Micro- and Nanotechnologies

1041-B - High-Precision Nanoliter Dispensing Technology for Blood Diagnosis Using Electroformed Nozzles

Monday, February 5, 2018
5:00 PM - 6:00 PM

Current emerging platforms for detecting rare biomarkers and tumor cells in the bloodstream have increasingly improved diagnostic sensitivity. Therefore, early signs of metabolic changes can be detected even with a tiny amount of biosample. Precisely manipulating and dispensing small-volume samples is one of the most crucial steps to acquiring reliable results. In particular, when the collected volume is extremely limited, the need for precise dispensing of submicroliter and nanoliter quantities is quite important. For example, dispensing volumes below 100 nL would be challenging because the dispensing process is dominated by interfacial adhesion and factors such as surface tension, capillary forces, and local microstructures that could affect the transferred volume. To achieve highly reliable diagnosis with a limited volume of blood sample, we developed a positive-displacement high-precision dispensing method by using a nickel electroformed nozzle with an inner diameter accuracy of 5 um or less. An electroformed nozzle was manufactured by casting an electroformed layer on a metallic wire, from which the wire was then subsequently removed. The inner diameter of the nozzle can be strictly controlled by using a wire with a highly precise outer diameter. The outside surface of the nozzle was hydrophobically treated. When a dispensing variation of 100 nL was evaluated by using a photometric method, the volume error of the dispensing system was 0.7%, i.e. 0.7 nL, which was found to be about four-fold less than that observed in conventional precision dispensers. The process of dispensing tiny drops by utilizing hydrophobic electroformed nozzles would effectively reduce liquid retention at the nozzle edge and increase precision. Furthermore, the glucose concentration in 100 nL of animal-based control serum was detected colorimetrically with enzymatic reactions. After dispensing a drop of serum while avoiding drying and mixing reagents, the concentration of glucose was measured. The coefficient variation of the analysis was approximately 3%, where the results suggest several biochemical panels should be precisely measured even from one drop of blood. This positive-displacement dispenser ensures zero cross-contamination and almost-zero dead volume and therefore would be useful for not only blood diagnosis but also bioscreening.

Takahiro Ando

Hitachi, Ltd., Research & Development Group, Tokyo, Japan

Takahiro Ando received the B.S., M.S. and Ph.D. degrees in Engineering from Keio University in 2008, 2010 and 2012, respectively. He was a Research Fellowship of the Japan Society for the Promotion of Science from 2010 to 2013 and Research Assistant of Keio Global COE program from 2010 to 2012. He has been a visiting researcher in Prof. Michael Hamblin's lab in the Wellman Center for Photomedicine, Mass. General Hospital, Harvard Medical School (Sep. 2010 to Feb. 2011) and in Prof. Elliot Botvinick's lab in the Beckman Laser Institute, UC Irvine (Dec. 2012 to Mar. 2013). His research interests include laser-mediated gene therapy and low-level laser therapy, especially for treatment of neurological diseases. After joining to Hitachi, Ltd. Research and Development group in Apr. 2013, he engages in cell discrimination technique using electron paramagnetic resonance (EPR) for regenerative medicine and develops various component technologies for biochemical clinical analyzers. His most recent publication is “Precise dispensing technology for point-of-care (POC) diagnosis with micro-volume blood.” ResearchGate: