Smart Materials and Chemical Systems

Biological intelligence (e.g., human beings) and artificial intelligence (AI) have made major changes to the world and major technological advances due to their versatility. However, these systems have their limitations. For example, electronic-based machines are not compatible in some environments (e.g., in a human body) and cannot be scaled down easily (e.g., batteries for powering the electronic systems). On the other hand, materials are generally perceived as “dumb”, like a block of brick or wood. Hence, our group proposed to create a new form of “chemical intelligence” in a perspective:

The ultimate aim is to construct small-scale self-powered autonomous systems that can sense, think, and respond to their environments—the creation of “chemical intelligence”. In general, the applications will include smart drug delivery systems, micro-machines, personalized medicine, methods for cancer treatment, highly sensitive diagnostic devices, and other biomedical applications. For example, one ultimate vision is to create a system that can explore the space in the human body, identify a localized problematic spot, and fix it autonomously—an intelligent system that can perform microsurgery.

We start from stimuli-responsive molecules. With the increasing complexity of our systems, the functions of our systems are also becoming multi-functional, stronger, and more intelligent.

Simple stimuli-responsive molecules are synthesized into advanced materials, which can fulfill basic functions (such as assembly/disassembly, change in materials properties, and change in size/shape).

By combining the advanced materials with basic functions, devices with complex functions are fabricated. Those devices can fulfill various complex functions: Analytical functions, Regulatory functions, and Practical functions. Even just one of each function can perform valuable tasks. By combining multiple functions with the design of the system, the transport of molecules, the use of interesting reactions that drive the dynamics of the systems, and the fabrication of these systems, these “intelligent” systems can potentially have applications in different technological areas such as drug delivery, membranes, actuators in microfluidics, and soft robotics.

Analytical function:

We fabricated different types of logic gates by assembling a combination of different types of stimuli-responsive hydrogels that change their size under the influence of one type of stimulus. Importantly, the preparation of these stimuli-responsive hydrogels is widely reported and technically simple. Through designing the geometry of the systems, we fabricated the YES, NOT, OR, AND, NOR, and NAND gates. Although the hydrogels respond to different types of stimuli, their outputs are the same: a change in size of the hydrogel. Hence, we show that the logic gates can be integrated easily (e.g., by connecting an AND gate to an OR gate). As a practical demonstration, we fabricated a standalone system with the size of a normal drug tablet (i.e., a “smart tablet”) that can analyze (or diagnose) different stimuli and control the release of a chemical (or drug) via the logic gates.¹

Regulatory function:

We propose to coat a stimuli-responsive hydrogel with silanized particles, which are known to be superhydrophobic. Thus, when the hydrogel is in its contracted state, it is superhydrophobic; when it expands, we found experimentally that it is superhydrophilic. In this way, it is possible to control the wettability by regulating the amount of the external stimulus. Therefore, instead of relying on materials that have the inherent ability to switch between hydrophobic and hydrophilic states under the influence of a stimulus, we use stimuli-responsive hydrogels as the medium that responds to the stimulus.²

This manuscript describes a signal‐amplifying mechanism for achieving highly sensitive yet low‐cost detection. The main component of the device is a hypersensitive material that consists of a stimuli‐responsive hydrogel coated with a thin layer of superhydrophobic nanoparticles. Initially, the superhydrophobic nanoparticles block the outflow of a dye (i.e., the impermeable state). When the stimuli‐responsive hydrogel expands after coming into contact with an appropriate stimulus, the dye diffuses through the gaps between the nanoparticles (i.e., the permeable state) and spread outward. The large outflow of dye (i.e., a clear visible readout) due to the small concentration or small amount (<1 µL) of chemicals added to the device produces the effect of signal amplification. Highly sensitive detection of concentration of as low as ∼10 nM is demonstrated. Fundamentally, the thin layer (<5 µm) of the superhydrophobic nanoparticles gives rise to a sharp impermeable‐permeable transition allowing for highly sensitive detection. This hypersensitive material provides the opportunity for the detection to be highly sensitive with many other desirable features such as low cost, portability, simplicity of fabrication and operation, capable of quantifying concentration (i.e., by measuring time), and able to perform complex analysis (e.g., via logic gates by detecting multiple signals).³Practical function:

We describe a fundamentally different approach: using the physical force of an expanding stimuli-responsive hydrogel to rupture cancer cells attached on its surface. Specifically, we coated temperature-responsive hydrogels with a layer of cell-adherent arginine-glycine-aspartate (RGD) peptides. The approach involved first allowing cancer cells to attach onto the surface of the hydrogels, and then applying a change in temperature. As the hydrogel underwent a chemical transformation and expanded due to the stimulus, the cancer cells attached to it ruptured. The results from staining the cells with trypan blue, observing them using SEM, and analyzing them using the MTT assay showed that both breast and lung cancer cells died after the hydrogel expanded; hence, we showed that this physical force from the expanding hydrogel is strong enough to rupture the cancer cells. In addition, the force derived from the expanding hydrogel was determined separately to be larger than that needed to rupture typical cells. This physical approach is conceptually simple, technically easy to implement, and potentially generalizable for rupturing a wide range of cells.⁴

We fabricate a general class of stimuli-responsive grippers that are soft and untethered. Each gripper is composed of a stimuli-responsive hydrogel with a hole in the middle for gripping onto objects and a layer of coating around its sides. Importantly, these grippers exert surprisingly large gripping forces relative to their weights—~10000, which is the highest reported in the literature for a gripper. This high load-to-weight ratio is unexpected because the stimuli-responsive hydrogel is soft, not tethered to any external supply of energy, and fabricated by simple methods. The approach is general: high load-to-weight ratios were achieved for both pH- and temperature- responsive hydrogels. As soft grippers, they gripped onto objects of different shapes and sizes easily. A class of soft untethered machines can be fabricated by assembling these soft grippers with different modular blocks of stimuli-responsive hydrogels for performing complex operations.⁵

Resources

1. Zhang, X.;Chen, L.;  Lim, K. H.;  Gonuguntla, S.;  Lim, K. W.;  Pranantyo, D.;  Yong, W. P.;  Yam, W. J. T.;  Low, Z.;  Teo, W. J.;  Nien, H. P.;  Loh, Q. W.; Soh, S., The Pathway to Intelligence: Using Stimuli-Responsive Materials as Building Blocks for Constructing Smart and Functional Systems. Adv Mater 2019, 31 (11), e1804540.
2. Huang, X.;Sun, Y.; Soh, S. In Stimuli-Responsive Surfaces for Tunable and Reversible Control of Wettability, Adv Mater, Jul 15; 2015; pp 4062-8.
3. Zhang, X.; Soh, S., Signal Amplification: A Sharp Impermeable-Permeable Transition for Highly Sensitive Low-Cost Detection. Advanced Materials Technologies 2018, 3 (6).
4. Fang, Y.;Tan, J.;  Lim, S.; Soh, S., Rupturing cancer cells by the expansion of functionalized stimuli-responsive hydrogels. NPG Asia Materials 2018, 10 (2), e465-e465.
5. Sun, Y.;Chen, L.;  Jiang, Y.;  Zhang, X.;  Yao, X.; Soh, S., Soft stimuli-responsive grippers and machines with high load-to-weight ratios. Materials Horizons 2019, 6 (1), 160-168.