Cell identification and enumeration are essential procedures within clinical and research laboratories. For over 150 years, quantitative investigation of body fluids such as counts of various blood cells has been an important tool for diagnostic analysis. With the current evolution of point-of-care diagnostics and precision medicine, cheap and precise cell counting technologies are in demand. This article reviews the timeline and recent notable advancements in cell counting that have occurred as a result of improvements in sensing including optical and electrical technology, enhancements in image processing capabilities, and contributions of micro and nanotechnologies. Cell enumeration methods have evolved from the use of manual counting using a hemocytometer to automated cell counters capable of providing reliable counts with high precision and throughput. These developments have been enabled by the use of precision engineering, micro and nanotechnology approaches, automation and multivariate data analysis. Commercially available automated cell counters can be broadly classified into three categories based on the principle of detection namely, electrical impedance, optical analysis and image analysis. These technologies have many common scientific uses, such as hematological analysis, urine analysis and bacterial enumeration. In addition to commercially available technologies, future technological trends using lab-on-a-chip devices have been discussed in detail. Lab-on-a-chip platforms utilize the existing three detection technologies with innovative design changes utilizing advanced nano/microfabrication to produce customized devices suited to specific applications.

As opposed to open surgery procedures, minimally invasive surgery (MIS) utilizes small skin incisions to insert a camera and surgical instruments. MIS has numerous advantages such as reduced postoperative pain, shorter hospital stay, faster recovery time, and reduced learning curve for surgical trainees. MIS comprises surgical approaches, including laparoscopic surgery, endoscopic surgery, and robotic-assisted surgery. Despite the advantages that MIS provides to patients and surgeons, it remains limited by the lost sense of touch due to the indirect contact with tissues under operation, especially in robotic-assisted surgery. Surgeons, without haptic feedback, could unintentionally apply excessive forces that may cause tissue damage. Therefore, incorporating tactile sensation into MIS tools has become an interesting research topic. Designing, fabricating, and integrating force sensors onto different locations on the surgical tools are currently under development by several companies and research groups. In this context, electrical force sensing modality, including piezoelectric, resistive, and capacitive sensors, is the most conventionally considered approach to measure the grasping force, manipulation force, torque, and tissue compliance. For instance, piezoelectric sensors exhibit high sensitivity and accuracy, but the drawbacks of thermal sensitivity and the inability to detect static loads constrain their adoption in MIS tools. Optical-based tactile sensing is another conventional approach that facilitates electrically passive force sensing compatible with magnetic resonance imaging. Estimations of applied loadings are calculated from the induced changes in the intensity, wavelength, or phase of light transmitted through optical fibers. Nonetheless, new emerging technologies are also evoking a high potential of contributions to the field of smart surgical tools. The recent development of flexible, highly sensitive tactile microfluidic-based sensors has become an emerging field in tactile sensing, which contributed to wearable electronics and smart-skin applications. Another emerging technology is imaging-based tactile sensing that achieved superior multi-axial force measurements by implementing image sensors with high pixel densities and frame rates to track visual changes on a sensing surface. This article aims to review the literature on MIS tactile sensing technologies in terms of working principles, design requirements, and specifications. Moreover, this work highlights and discusses the promising potential of a few emerging technologies towards establishing low-cost, high-performance MIS force sensing.

This paper aimed to develop a miniaturized tactile sensor capable of measuring force and force position in minimally invasive surgery. The in situ measurement of tactile information is a step forward toward restoring the loss of the sense of touch that has occurred due to shift from traditional to minimally invasive surgeries. The sensor was designed such that it can sense low forces which could be comparable to those produced by pulsating delicate arteries, yet can withstand high forces comparable to grasping forces. The influence of some hidden anatomical features, such as lumps, voids, and arteries, on the stress distribution at the grasping surface was studied. In this paper, the capability of the sensor to determine and locate any point load was also investigated. The proposed sensor was designed and manufactured to be highly sensitive, using polyvinylidene fluoride (PVDF). The microfabrication procedure of the sensor, including corner compensation for toothlike projections and patterning of PVDF film, was discussed. The micromachined sensor was tested, and the experimental results were compared with the results of 3-D finite element modeling.

Particle/cell separation in heterogeneous mixtures including biological samples is a standard sample preparation step for various biomedical assays. A wide range of microfluidic-based methods have been proposed for particle/cell sorting and isolation. Two promising microfluidic platforms for this task are microfluidic chips and centrifugal microfluidic disks. In this review, we focus on particle/cell isolation methods that are based on liquid centrifugation phenomena. Under this category, we reviewed particle/cell sorting methods which have been performed on centrifugal microfluidic platforms, and inertial microfluidic platforms that contain spiral channels and multi-orifice channels. All of these platforms implement a form of centrifuge-based particle/cell separation: either physical platform centrifugation in the case of centrifugal microfluidic platforms or liquid centrifugation due to Dean drag force in the case of inertial microfluidics. Centrifugal microfluidic platforms are suitable for cases where the preparation step of a raw sample is required to be integrated on the same platform. However, the limited available space on the platform is the main disadvantage, especially when high sample volume is required. On the other hand, inertial microfluidics (spiral and multi-orifice) showed various advantages such as simple design and fabrication, the ability to process large sample volume, high throughput, high recovery rate, and the ability for multiplexing for improved performance. However, the utilization of syringe pump can reduce the portability options of the platform. In conclusion, the requirement of each application should be carefully considered prior to platform selection.

The concept of fluidic multipoles, in analogy to electrostatics, has long been known as a particular class of solutions of the Navier-Stokes equation in potential flows; however, experimental observations of fluidic multipoles and of their characteristics have not been reported yet. Here we present a two-dimensional microfluidic quadrupole and a theoretical analysis consistent with the experimental observations. The microfluidic quadrupole was formed by simultaneously injecting and aspirating fluids from two pairs of opposing apertures in a narrow gap formed between a microfluidic probe and a substrate. A stagnation point was formed at the centre of the microfluidic quadrupole, and its position could be rapidly adjusted hydrodynamically. Following the injection of a solute through one of the poles, a stationary, tunable, and movable—that is, 'floating'—concentration gradient was formed at the stagnation point. Our results lay the foundation for future combined experimental and theoretical exploration of microfluidic planar multipoles including convective–diffusive phenomena.

During nervous system development, gradients of Sonic Hedgehog (Shh) and Netrin-1 attract growth cones of commissural axons toward the floor plate of the embryonic spinal cord. Mice defective for either Shh or Netrin-1 signaling have commissural axon guidance defects, suggesting that both Shh and Netrin-1 are required for correct axon guidance. However, how Shh and Netrin-1 collaborate to guide axons is not known. We first quantified the steepness of the Shh gradient in the spinal cord and found that it is mostly very shallow. We then developed an in vitro microfluidic guidance assay to simulate these shallow gradients. We found that axons of dissociated commissural neurons respond to steep but not shallow gradients of Shh or Netrin-1. However, when we presented axons with combined Shh and Netrin-1 gradients, they had heightened sensitivity to the guidance cues, turning in response to shallower gradients that were unable to guide axons when only one cue was present. Furthermore, these shallow gradients polarized growth cone Src-family kinase (SFK) activity only when Shh and Netrin-1 were combined, indicating that SFKs can integrate the two guidance cues. Together, our results indicate that Shh and Netrin-1 synergize to enable growth cones to sense shallow gradients in regions of the spinal cord where the steepness of a single guidance cue is insufficient to guide axons, and we identify a novel type of synergy that occurs when the steepness (and not the concentration) of a guidance cue is limiting. During development of the nervous system, axons are propelled by the growth cone, a motile structure that is specialized to detect the direction of concentration gradients of guidance cues. Although it is known that commissural axons—those that cross the midline from one side of the nervous system to the other—of the spinal cord are guided by multiple cues simultaneously, it is unclear whether they integrate multiple guidance cues and, if that is the case, the advantage of doing so. In the developing spinal cord, the gradients of the guidance cues are shallow and, thus, their direction is difficult to determine. We hypothesize that under these circumstances, a combination of cues could be used synergistically by the growth cone. To test this hypothesis, we built a microfluidic gradient generator capable of simulating the shallow gradients that growth cones encounter in the developing spinal cord. Using this guidance assay, we demonstrated that commissural axons are best at reorienting themselves in the steepest part of a gradient of Shh or Netrin, two guidance cues that these axons encounter in the spinal cord. We then challenged axons with combined gradients of both cues. At low gradient steepness, we observed synergy in their turning response and in the asymmetry of the shared downstream signaling molecules Src-family kinases (SFKs). We therefore propose a model in which SFKs integrate distinct signaling pathways, and we define this as steepness-limited synergy.