Editorial Zhang, Bills & Manicke


small-molecule drugs to diffuse back and forth between flow channels and the insert wells. Multiple pharma- cokinetic profiles were generated simultaneously by using this device and the volume consumption was reduced from liters to milliliters, in comparison with diffusion-based dynamic in vitro models.


attention as an alternative method to fabricate analytical devices.


“3D printing has recently attracted ” In our laboratory, we are working to develop inex-


pensive disposable cartridges that address the entire bioanalytical workflow including sample collection, transportation/storage, sample preparation and anal- ysis. As an example of this approach, we have been investigating paper-spray MS, in which biofluids sam- ples are deposited and stored on paper. Extraction and ionization are then carried out directly from the dried biofluid spot on the paper without additional sample preparation (CITE). We have begun using 3D print- ing to generate prototype sampling cartridge as well as various devices to facilitate the experiments. This equipment is not necessarily complicated. It could be as simple as a piece of plastic to hold blood samples in a certain way while drying or more complex like a new disposable cartridge designed to perform automatic sample preconcentration. In the past, we would manufacture these objects by


using a milling machine to carve the desired piece out of blocks of plastic. Advantages of the milling machine include its relatively low cost (a quality benchtop milling machine can be purchased for ∼US$1000) and the wide range of materials can be machined, including metal and plastics with good solvent resistance, such as Del- rin®


and Teflon® . However, machining parts was often


time consuming, and required planning and foresight to work within the limits of what could be done with a milling machine. Parts also had to be machined one at a time. Paper spray cartridges made using a milling machine required an afternoon of tedious progress to cut out a slot for the paper using a narrow and fragile milling bit. As a result, only one or two cartridges would be made and would require cleaning between each


sample. Recently, a service opened on campus that pro- vided access to a number of different types and brands of 3D printers. Using a sufficiently high-resolution 3D printer, a cartridge with the desired dimensions can be printed in an hour. In addition, modifications to the design require only as much time as changing the 3D model and printing off new cartridges. This has allowed for rapid prototyping with multiple iterations and the ability to print off multiple cartridges to allow an entire experiment to be set up at once without the tedium of cleaning the cartridges between each analytical run. In a recent experiment, for example, a special mem-


brane had to be held against a small piece of paper while plasma wicked through from whole blood [15]. The membrane was prone to ripping so a special holder was designed capable of holding the membrane gently dur- ing the experiment. Initially the holder was machined from three pieces of plastic taking around 2 days to design and manufacture by hand. The experiment had to be modified, and the original holder no longer worked as desired. A second holder was produced using 3D printing. Using a free 3D modeling program, it took around 2 h to model the holder and two more hours to print five copies of the holder to scale-up the experi- ment. This speed and ease of making copies has proved useful in a number of experiments. In another example, a paper spray cartridge with


Figure 1. Paper spray cartridge integrated with solid phase extraction. (A) Prototype made by milling machine. (B) 3D-printing cartridge.


10 Bioanalysis (2017) 9(4)


integrated solid phase extraction (SPE) was developed in our laboratory recently for the selective and sensi- tive detection of small molecule drugs in plasma [16]. The cartridge consisted of two parts that were assem- bled together, as shown in Figure 1A. Using a milling machine, it took us about a week to produce enough cartridges to analyze a batch of samples for quantita- tive analysis, in which dozens of samples needed to be prepared and tested at the same time. In addition, the milling process had to be done carefully to ensure reproducibility among cartridges. However, there is no such reproducibility issue in 3D-printed cartridges. Moreover, 3D printing speeds up the commercializa- tion process of the SPE cartridge. In order to achieve an automatic high-throughput analysis, we redesigned the SPE cartridge to make it work in a Prosolia (IN, USA) paper spray autosampler [Unpublished D ata ]. The redesigned 3D-printed SPE cartridge could be printed within 2 h, costing only US$2. As shown in Figure 1B, the new cartridge has a smaller size in comparison with its prototype, the same position to apply spray solvent and spray voltage as a Prosolia paper spray cartridge, and is assembled from four parts with more compli- cated structure that would be impossible to produce by a milling machine. Advantages of 3D printing for fabrication of bio- analysis prototypes include reproducibility, high preci-


future science group


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