Ultrasensitive biosensor using molybdenite semiconductor outshines graphene

74-fold higher sensitivity than graphene; may lead to "true evidence-based, personalized medicine"
September 9, 2014

Concept art of a biosensor based on a molybdenum disulfide field-effect transistor demonstrated by UCSB researchers with ability to detect ultra-low (femtomolar) concentrations with sensitivity that is 74-fold higher than that of graphene FET biosensors (credit: Peter Allen/ACS Nano)

An atomically thin, two-dimensional, ultrasensitive semiconductor material for biosensing developed by University of California Santa Barbara (UCSB) researchers promises to push the boundaries of biosensing technology in many fields, from health care to environmental protection to forensic industries.

It’s based on molybdenum disulfide, or molybdenite (MoS2), which KurzweilAI has been covering as an alternative to graphene.

Molybdenum disulfide — commonly used as a dry lubricant — surpasses graphene’s already high sensitivity, offers better scalability, and lends itself to high-volume manufacturing, the researchers say. Results of their study have been published in ACS Nano.

“This invention has established the foundation for a new generation of ultrasensitive and low-cost biosensors that can eventually allow single-molecule detection — the holy grail of diagnostics and bioengineering research,” said Samir Mitragotri, co-author and professor of chemical engineering and director of the Center for Bioengineering at UCSB.

The MoS2 band-gap advantage over graphene

The key, according to UCSB professor of electrical and computer engineering Kaustav Banerjee, who led this research, is MoS2’s band gap, a characteristic of a material that determines its electrical conductivity (the minimum amount of energy required for conduction; i.e., for an electron to break free of its bound state in a material — the gap between bound and free).

Semiconductor materials have a small but nonzero band gap and can be switched between conductive and insulated states controllably. The larger the band gap, the better its ability to switch states and to insulate leakage current in an insulated state. MoS2’s wide band gap allows current to travel but also prevents leakage and results in more sensitive and accurate readings.

Graphene has attracted wide interest as a biosensor due to its two-dimensional structure (which allows for excellent electrostatic control of the transistor channel by the gate) and its high surface-to-volume ratio. However, the sensitivity of a field-effect transistor (FET) biosensor based on graphene is fundamentally limited by graphene’s zero (fully conductive) band gap, which results in increased leakage current, leading to reduced sensitivity, explained Banerjee, who is also the director of the Nanoelectronics Research Lab at UCSB.

Graphene has been used, among other things, in FETs — devices that regulate the flow of electrons through a channel via a vertical electric field directed into the channel by a terminal called a “gate,” allowing for amplification and switching.

How biosensing works

(Top) schematic diagram of the chip (S: source; D: drain); (Left) Optical enlarged image of the MoS2 FET biosensor showing extended electrodes (yellow) made of Ti/Au and a biological sample (blue) between them; scale bar, 10 μm; right: optical image of full biosensor device with macrofluidic channel for containing the electrolyte (credit: Peter Allen/ACS Nano)

In biosensing, the FET’s physical gate is removed, and the current in the channel is modulated by the binding between embedded receptor molecules and the charged target biomolecules to which they are exposed. Graphene has received wide interest in the biosensing field and has been used to line the channel and act as a sensing element whose surface potential (or conductivity) can be modulated by the interaction (known as conjugation) between the receptor and target molecules, resulting in net accumulation of charges over the gate region.

However, the research team notes, despite graphene’s excellent characteristics, its performance is limited by its zero band gap. So electrons travel freely across a graphene FET — hence, it cannot be “switched off” — which results in current leakages and higher potential for inaccuracies.

Much research in the graphene community has been devoted to compensating for this deficiency, either by patterning graphene to make nanoribbons or by introducing defects in the graphene layer — or using bilayer graphene stacked in a certain pattern that allows band gap opening upon application of a vertical electric field — for better control and detection of current.

“Monolayer or few-layer MoS2 both have a key advantage over graphene for designing an FET biosensor: they have a relatively large and uniform band gap (1.2-1.8 eV, depending on the number of layers), which significantly reduces the leakage current and increases the abruptness of the turn-on behavior of the FETs, thereby increasing the sensitivity of the biosensor,” said Banerjee.

‘The best of everything’

Additionally, according to Deblina Sarkar, a PhD student in Banerjee’s lab and the lead author of the article, two-dimensional MoS2 is relatively simple to manufacture.

“While one-dimensional materials such as carbon nanotubes and nanowires also allow excellent electrostatics and at the same time possess band gap, they are not suitable for low-cost mass production due to their process complexities,” she said. “Moreover, the channel length of an MoS2 FET biosensor can be scaled down to the dimensions similar to those of small biomolecules such as DNA or small proteins, [while] still maintaining good electrostatics, which can lead to high sensitivity even for detection of single quanta of these biomolecular species,” she added.

“In fact, atomically thin MoS2 provides the best of everything: great electrostatics due to their ultra-thin body, scalability (due to large band gap), as well as patternability due to their planar nature that is essential for high-volume manufacturing,” said Banerjee.

The MoS2 biosensors demonstrated by the UCSB team have already provided ultrasensitive and specific protein sensing with a sensitivity of 196 even at 100 femtomolar (a billionth of a millionth of a mole) concentrations. This protein concentration is similar to one drop of milk dissolved in a hundred tons of water. An MoS2-based pH sensor achieving sensitivity as high as 713 for a pH change by one unit along with efficient operation over a wide pH range (3–9) is also demonstrated in the same work.

“This transformative technology enables highly specific, low-power, high-throughput physiological sensing that can be multiplexed to detect a number of significant, disease-specific factors in real time,” commented Scott Hammond, executive director of UCSB’s Translational Medicine Research Laboratories.

Biosensors based on conventional FETs have been gaining momentum as a viable technology for the medical, forensic and security industries since they are cost-effective compared to optical detection procedures. Such biosensors allow for scalability and label-free detection of biomolecules — removing the step and expense of labeling target molecules with florescent dye. “In essence,” continued Hammond, “the promise of true evidence-based, personalized medicine is finally becoming reality.”

“This demonstration is quite remarkable,” said Andras Kis, professor at École Polytechnique Fédérale de Lausanne in Switzerland and a leading scientist in the field of 2D materials and devices, who is not connected to the project. “At present, the scientific community worldwide is actively seeking practical applications of 2D semiconductor materials such as MoS2 nanosheets. Professor Banerjee and his team have identified a breakthrough application of these nanomaterials and provided new impetus for the development of low-power and low-cost ultrasensitive biosensors.”

However, for commercial (high volume) manufacturing, the MoS2 films must be synthesized over large (wafer) scale, the researchers note. There have been reports already on such efforts via chemical vapor deposition, but not yet at wafer scale.  It will probably take a few more years for the synthesis technique to fully mature, they suggest.

Research on this project was supported by the National Science Foundation, the California NanoSystems Institute at UCSB, and the Materials Research Laboratory at UCSB, a National Science Foundation MRSEC.


Abstract of ACS Nano paper

Biosensors based on field-effect transistors (FETs) have attracted much attention, as they offer rapid, inexpensive, and label-free detection. While the low sensitivity of FET biosensors based on bulk 3D structures has been overcome by using 1D structures (nanotubes/nanowires), the latter face severe fabrication challenges, impairing their practical applications. In this paper, we introduce and demonstrate FET biosensors based on molybdenum disulfide (MoS2), which provides extremely high sensitivity and at the same time offers easy patternability and device fabrication, due to its 2D atomically layered structure. A MoS2-based pH sensor achieving sensitivity as high as 713 for a pH change by 1 unit along with efficient operation over a wide pH range (3–9) is demonstrated. Ultrasensitive and specific protein sensing is also achieved with a sensitivity of 196 even at 100 femtomolar concentration. While graphene is also a 2D material, we show here that it cannot compete with a MoS2-based FET biosensor, which surpasses the sensitivity of that based on graphene by more than 74-fold. Moreover, we establish through theoretical analysis that MoS2 is greatly advantageous for biosensor device scaling without compromising its sensitivity, which is beneficial for single molecular detection. Furthermore, MoS2, with its highly flexible and transparent nature, can offer new opportunities in advanced diagnostics and medical prostheses. This unique fusion of desirable properties makes MoS2 a highly potential candidate for next-generation low-cost biosensors.