Multicomponent High-throughput Drug Screening via Inkjet Printing to Verify the Effect of Immunosuppressive Drugs on Immune T Lymphocytes

Abstract

High-throughput drug screening based on a multi-component array can be used to identify a variety of interaction between cells and drugs for suitable purposes. The signaling of immune cells is affected by specific proteins, diverse drug combinations, and certain immunosuppressive drugs. The effect of a drug on an organism is usually complex and involves interactions at multiple levels. Herein, we developed a multilayer fabricating system through the high-throughput assembly of nanofilms with inkjet printing to investigate the effects of immunosuppressive drugs. Immunosuppressive drugs or agents occasionally cause side effects depending on drug combinations or a patient's condition. By incorporating various drug combinations for understanding interaction between drugs and immune cells, we were able to develop an immunological drug screening kit with immunosuppressive drugs. Moreover, the ability to control the combination of drugs, as well as their potential for high-throughput preparation should be of great benefit to the biomedical and bioanalytical field.

Figure 1

Schematic illustration of a three layered drug screening kit to effectively analyze various effects of medication for immunosuppression with inkjet printed biocompatible nanofilms including various drug combinations (The figure including inkjet printing image, Human torso image, the Immune T-Cell and the drug screen kit was drawn by M.C).

Figure 2

(a) Schematic illustration of fabrication of printed (PLL/HA/drugs) trilayer based mutilayer nanofilms for the high-throughput immunosuppressive drug screening and chemical structures of immunosuppressive drugs (MPA, RAPA, Cyc A) (The figure was drawn by M.C). (b) Digital image of a 96-well plate as a printed shaped on the silicon wafer. (c) Thickness profile analysis of (PLL/HA)_n, _{(n = bilayers)} printed multilayer nanofilms as measured by a mechanical profilometer.

Figure 3

(a) Decreasing film thickness of printed (PLL/HA/FITC)_{n(n = number of trilayers)} trilayer-based nanofilms over time. (b) Normalized and (c) total release profiles of printed (PLL/HA/FITC)_{10, 30} nanofilms during 30 h.

Figure 4

(a) Schematic illustration of the high-throughput drug screening process (The figure was drawn by M.C). Phytohaemagglutinin (PHA) treatment (b) before and (c) after each of the immunosuppressive drug tests for confirmation of the effects of immunosuppressive drugs in the printen nanofilms.

Figure 5

(a) Combinations of immunosuppressive drugs on the single plate (The figure was drawn by M.C). (b) Amounts of IL-2 released by interaction between immune T cells and immunosuppressive drugs. (c) IL-2 level comparison between the multilayer nanofilms and manual immunosuppressive drug combination test.