High throughput miniature drug-screening platform using bioprinting technology

Abstract

In the pharmaceutical industry, new drugs are tested to find appropriate compounds for therapeutic purposes for contemporary diseases. Unfortunately, novel compounds emerge at expensive prices and current target evaluation processes have limited throughput, thus leading to an increase of cost and time for drug development. This work shows the development of the novel inkjet-based deposition method for assembling a miniature drug-screening platform, which can realistically and inexpensively evaluate biochemical reactions in a picoliter-scale volume at a high speed rate. As proof of concept, applying a modified Hewlett Packard model 5360 compact disc printer, green fluorescent protein expressing Escherichia coli cells along with alginate gel solution have been arrayed on a coverslip chip under a repeatable volume of 180% ± 26% picoliters per droplet; subsequently, different antibiotic droplets were patterned on the spots of cells to evaluate the inhibition of bacteria for antibiotic screening. The proposed platform was compared to the current screening process, validating its effectiveness. The viability and basic function of the printed cells were evaluated, resulting in cell viability above 98% and insignificant or no DNA damage to human kidney cells transfected. Based on the reduction of investment and compound volume used by this platform, this technique has the potential to improve the actual drug discovery process at its target evaluation stage.

A comprehensive review on droplet-based bioprinting: Past, present and future

“…Subsequently, Nakamura's group successfully fabricated viable 3D tubular tissue constructs using a commercially available electrostatic DOD inkjet printer [31]. Later, several research groups have successfully adopted DBB technologies for bioprinting of a wide array of cells for various purposes, including but not limited to, bioprinting for stem cell research [17,[32][33][34], tissue engineering [17,24,35,36], controlled release [37], transplantation [24,35], drug screening [38], high-throughput arrays [39], and cancer research [36,40].…”

“…Highly complex heterocellular tissue constructs with different compositions of biologics (i.e., biomaterials, cells, growth factors, drugs, and genes) can be easily patterned when compared to extrusion-and laser-based bioprinting techniques as it is highly challenging to generate heterogeneity in a delicate manner using extrusion-based bioprinting and incorporating multiple types of biologics in laser-based bioprinting is difficult. While DBB has a process resolution higher than that of extrusion-based bioprinting and possesses a greater versatility in incorporating multiple biologics, DBB has attracted several researchers in the bioprinting community as well as researchers adopting bioprinting technology in other field of studies such as regenerative medicine and pharmaceutics [38,124]. Moreover, it has a reasonable resolution comparable to laser-based bioprinting, which allows better control on the geometry and size Droplet-based bioprinters are highly versatile and affordable, where a simple HP printer can be easily modified and used as a bioprinter [125].…”

“…27 ovarian tumor tissue [38]. Various tissue types fabricated using DBB and other bioprinting modalities are compared in Table 4.…”

“…The generated micro-array was then stimulated with different environmental conditions, such as temperature, in order to investigate the effect of the applied stimuli on cell fate. In a more recent study, Xu et al presented an inkjet-based bioprinting approach to assemble a high-throughput miniature drug-screening platform [38]. A modified HP model 5360 compact disc printer was used to bioprint E. coli-laden alginate to …”

Tissue Engineering

“…Examples of applications under development include: directed differentiation of stem cells [93,94]; drug-screening in tissue-like contexts [95]; generation of tissue constructs with growth factor gradients [81] and tailored mechanical properties [89]; production of blood vessel substitutes [96]; and direct in vivo repair of tissues such cartilage and skin [97,98]. Eventually, bioprinting may prove the method of choice to generate whole organ constructs comprising multiple cell types and microenvironments.…”