**2. Implantable sensors for biomedical applications**

Recent developments in biomedical sensors and state-of-the-art CMOS technologies have led to the realization of minimally invasive implantable biomedical sensors for continuous monitoring of the patients. A continuous monitoring system allows the doctors to investigate the medical data of the patient online and thus provides savings in both time and money. The data acquired by the sensor from frequent monitoring also helps the hospital to efficiently record the medical history of a patient for future references. Figure 1 represents a detailed implantable sensor system with the combination of different biosensors and integrated circuits (ICs) which are designed to be implanted underneath the skin. Sub-micron CMOS technologies offer various advantages such as small form factor and reliable operation which make them very suitable for implantable medical applications. Biosensors on this platform include glucose, lactose, oxygen and pH sensors, etc. The state of the art research on implantable biosensor system focuses on its small form factor and light-weight for easy integration and biological safety [1]. Even though the development of deep sub-micron CMOS processes has significantly brought down the overall chip area, still the power unit such as lithium ion battery takes up a substantial area of the overall system. Therefore elimination of the battery as the power source can potentially reduce the system area significantly. Batteries also impose a potential risk of leakage which might result in serious health hazards to the patient and require periodic replacement. An eco-friendly solution of this potential problem involves the devel‐ opment of more efficient wireless powering methods or the design of low-power ICs. In contrast to a battery operated system, wireless powered system eliminates the hassle of frequent replacement of the power source and can be considered as a minimally invasive option with no risk of infection [1] [2]. Previously reported works present the use of inductive coupling (i.e. inductive link) [1] and optical coupling (i.e. solar cells) [2] as potential wireless powering approaches. A noninvasive, reliable, and efficient power supply along with a reliable data communication interface is a potentially important feature that an implantable sensor must possess.

A biosensor usually consists of an electrochemical sensor which generates an electrical signal that corresponds to the concentration of a particular electrolyte. Readout electronics such as potentiostats (amperometric or voltametric electrochemical sensors) help maintain a constant potential difference between two electrodes to facilitate the chemical reaction to take place and provide output in the form of a current (amperometric) or a voltage (voltametric) signal. A typical potentiostat consists of three electrodes: a working electrode (WE), a counter electrode (CE), and a reference electrode (RE). The potential difference between the working and the reference electrodes stimulates the chemical reaction and the counter electrode provides the corresponding output current signal, which is then delivered to the signal processing unit (SPU). The SPU modulates the data so that it can be transmitted outside of the body wirelessly to a receiver, which can be a smart phone or a similar electronic device. Peripheral ICs such as power supply units, sensor activation circuits etc. are also integrated together to realize this scheme on a system-on-a-chip (SoC) platform.

**Figure 1.** Implantable biosensor system (inside the dashed red rectangle) [3].

## **3. Low-power circuit design techniques**

**2. Implantable sensors for biomedical applications**

must possess.

152 Advances in Bioengineering

scheme on a system-on-a-chip (SoC) platform.

Recent developments in biomedical sensors and state-of-the-art CMOS technologies have led to the realization of minimally invasive implantable biomedical sensors for continuous monitoring of the patients. A continuous monitoring system allows the doctors to investigate the medical data of the patient online and thus provides savings in both time and money. The data acquired by the sensor from frequent monitoring also helps the hospital to efficiently record the medical history of a patient for future references. Figure 1 represents a detailed implantable sensor system with the combination of different biosensors and integrated circuits (ICs) which are designed to be implanted underneath the skin. Sub-micron CMOS technologies offer various advantages such as small form factor and reliable operation which make them very suitable for implantable medical applications. Biosensors on this platform include glucose, lactose, oxygen and pH sensors, etc. The state of the art research on implantable biosensor system focuses on its small form factor and light-weight for easy integration and biological safety [1]. Even though the development of deep sub-micron CMOS processes has significantly brought down the overall chip area, still the power unit such as lithium ion battery takes up a substantial area of the overall system. Therefore elimination of the battery as the power source can potentially reduce the system area significantly. Batteries also impose a potential risk of leakage which might result in serious health hazards to the patient and require periodic replacement. An eco-friendly solution of this potential problem involves the devel‐ opment of more efficient wireless powering methods or the design of low-power ICs. In contrast to a battery operated system, wireless powered system eliminates the hassle of frequent replacement of the power source and can be considered as a minimally invasive option with no risk of infection [1] [2]. Previously reported works present the use of inductive coupling (i.e. inductive link) [1] and optical coupling (i.e. solar cells) [2] as potential wireless powering approaches. A noninvasive, reliable, and efficient power supply along with a reliable data communication interface is a potentially important feature that an implantable sensor

A biosensor usually consists of an electrochemical sensor which generates an electrical signal that corresponds to the concentration of a particular electrolyte. Readout electronics such as potentiostats (amperometric or voltametric electrochemical sensors) help maintain a constant potential difference between two electrodes to facilitate the chemical reaction to take place and provide output in the form of a current (amperometric) or a voltage (voltametric) signal. A typical potentiostat consists of three electrodes: a working electrode (WE), a counter electrode (CE), and a reference electrode (RE). The potential difference between the working and the reference electrodes stimulates the chemical reaction and the counter electrode provides the corresponding output current signal, which is then delivered to the signal processing unit (SPU). The SPU modulates the data so that it can be transmitted outside of the body wirelessly to a receiver, which can be a smart phone or a similar electronic device. Peripheral ICs such as power supply units, sensor activation circuits etc. are also integrated together to realize this

Even though the amplitude of the signal generated by the implantable biosensors depends on the concentration of various physiological parameters, nonetheless the signal needs to be amplified and converted to a digital signal for further processing. Low-voltage and low-power circuit design techniques are required to be employed in the design of the signal processing circuitry of the implantable devices for long-term reliable operations. Depending on the application the most appropriate circuit topology needs to be chosen to meet the design challenges. Various innovative low-power circuit design methodologies have appeared in literatures to meet the requirement of long term operations. Their working principles are discussed in the following sections.

From the perspective of a circuit designer, employing of short-channel transistors is an appealing and efficient method to reduce the SoC chip area. The added advantage of these transistors is that the power supply voltage also downscales proportionally with the reduction of the transistor channel length. Thus hot electron effect and time-dependent dielectric breakdown (TDDB) [4] do not deteriorate the robustness and reliability of the devices. However, the threshold voltage, VT of the MOSFET does not scale down as aggressively as the channel length or the power supply voltage [5], which puts a constraint on the number of transistors that can be cascaded in a given process. Some of the techniques for low-power circuit design include bulk-or body-driven technique, floating gate technique, subthreshold biasing scheme of the transistors etc. The following sections summarize various low-power circuit design techniques reported in literature.

#### **3.1. Bulk-driven technique**

The bulk (or body-)-driven scheme is a technique that allows circuit designers to implement ultra-low voltage and ultra-low power system. In the bulk-driven circuit design scheme, the bulk or the body terminal of a MOSFET is enabled as an AC input. The gate of the device is kept at a certain potential so that the transistor is 'on' during the entire operation. This technique eliminates the threshold voltage limitation mentioned earlier and helps achieve ultra-low supply voltage requirement while cascading a good number of transistors. Circuit designers have used this technique to design a low-voltage, low-power amplifier with a supply voltage of as low as 1 V [3]. A major drawback of this approach is the lower body transcon‐ ductance (*g*mb). In addition, the bulk-driving voltage needs to be kept within a certain range so that the body diodes of the MOSFET are reverse-biased during the variation of the AC input signal of the body terminal. Therefore, this technique can only be applied to a limited number of applications [6].

#### **3.2. Floating gate technique**

Although the implementation of the floating gate technique is mostly seen in the integrat‐ ed memory cell applications, it can also be used for designing low-power circuits for implantable sensors. Floating gate is the polysilicon gate of the MOSFET that is surround‐ ed by silicon dioxide (SiO2). Once the charge has been deposited on the floating gate, it can be stored permanently. Therefore this technique is suitable for flash memory cells. The amount of this charge can be adjusted by an ultraviolet (UV) light or a large gate volt‐ age. The stored charge on the floating gate can be used to reduce the threshold voltage of the transistor. Thus this technique helps reduce the DC supply voltage requirement as well as the total power consumption [7].

#### **3.3. Subthreshold design technique**

Another method that is being used to implement the low-power circuit is the subthreshold design technique. In subthreshold region (or weak inversion region) design, the gate-to-source voltage of the MOSFET is biased below the threshold voltage (*V*GS *≤ V*TH) of the transistors. This level of gate-to-source voltage can weakly invert the transistor channel underneath the gate. This process of inversion of the channel is also known as weak inversion. Previously it was assumed by the researchers that this condition put the MOSFET in to cut-off region and therefore no current flows through the device. Now, it is well known that there is actually a small current that flows through the channel of the MOSFET mostly due to the diffusion of electrons from the drain to the source. A common expression for this subthreshold current of a MOSFET is shown in equation 1:

$$\mathbf{I}\_{\rm D} = \mathbf{I}\_{\rm D0} \xleftarrow{W} \mathbf{e}^{\left(\frac{V\_{\rm cs} - V\_{\rm trt}}{nU\_{\rm tr}}\right)} \tag{1}$$

Where *I*D0 is the current that flows when the gate-to-source voltage is equal to the threshold voltage, *n* is a technology specific slope parameter, and *U*<sup>T</sup> is thermal voltage (*U*<sup>T</sup> *≈ kT/q ≈ 26 mV* at room temperature where *k* is the Boltzmann constant, *T* is the temperature in Kelvin and *q* is the charge of an electron which is equal to 1.6×10-19 coulomb). The exponential relationship between the drain current and the gate-to-source voltage causes subthreshold biased circuits to be extremely sensitive to noise and matching. In comparison with the strong inversion circuit design technique that requires the gate-to-source voltage of the transistor to be much higher than the threshold voltage, this technique can achieve higher transconductance efficiency for the same level of current. Combined with rational circuit design and layout approach, this method can be used for implementing low-power analog circuits for implantable sensors.
