Blood cleaner on-chip design for artificial human kidney manipulation.

A novel design of a blood cleaner on-chip using an optical waveguide known as a PANDA ring resonator is proposed. By controlling some suitable parameters, the optical vortices (gradient optical fields/wells) can be generated and used to form the trapping tools in the same way as optical tweezers. In operation, the trapping force is formed by the combination between the gradient field and scattering photons by using the intense optical vortices generated within the PANDA ring resonator. This can be used for blood waste trapping and moves dynamically within the blood cleaner on-chip system (artificial kidney), and is performed within the wavelength routers. Finally, the blood quality test is exploited by the external probe before sending to the destination. The advantage of the proposed kidney on-chip system is that the unwanted substances can be trapped and filtered from the artificial kidney, which can be available for blood cleaning applications.

Introduction

Human kidneys are important excretory organs whose main functions are maintaining the concentrations of various ions and other important substances constant, and the removal of wastes and other unwanted substances in the urine.1 One living human kidney has from 300,000 to over 1,000,000 nephrons,2 the number of which is related to birth weights.3 Each nephron comprises two parts, namely the glomerulus and the tubules. The glomerulus is comprised of capillary vessels and the blood plasma is filtered from the blood through the porous wall of the vessels.1

Chronic kidney disease (CKD) is a worldwide health problem increasing dramatically in several countries.4,5 This is a key focus for health care planning, even in the developed world, in which many clinical organizations have been established for the development of hemodialysis devices and methods.6–8 CKD and acute renal failure occurs when one suffers from gradual and usually permanent loss of kidney function over time and loses the ability to filter and remove waste and extra fluids from the body.

Hemodialysis is the process of removing waste products from the blood. This removal is normally done by the kidneys. If they are impaired and require treatment,9 a dialysis machine (artificial kidney) can perform a similar function. The invention, manufacture, and implantation of the artificial kidney has been developed from the human organ.10–14 But artificial kidney dialysis has several disadvantages such as time wastage for blood dialysis (2–4 hours/visit), and the need for patients to visit the hospital every week (2–3 times/week). This has led researchers and inventors to develop an implantable artificial kidney,15 which would increase convenience.

Optical trapping was first invented by Ashkin.16 It emerged as a powerful tool with wide-reaching applications in biology, physics, engineering, and medicine.17 The ability of optical trapping and manipulation of viruses, living cells, and bacteria without organelle damage18 by laser radiation pressure has been demonstrated.19,20 This is specific to medicine and the application of nanotechnology. Lee et al21,22 carried out a single red blood cell (RBC) deformability test, which was performed by using optical trapping plastic in a microfluidics chip, and a lab-on-a-chip for RBC transportation in the capillary network to circulate oxygen and carbon dioxide throughout the human body.23 The optical trapping manipulation molecules in the liquid-core waveguide and its application to drug delivery has been reported by Suwanpayak et al,24 in which a PANDA ring resonator is used to form, transmit, and receive the microscopic volume of the drug by controlling the ring parameters. This microscopic volume can be trapped and transported dynamically within the wavelength router or network.

Recently, the promising technique of microscopic volume trapping and transportation within an add/drop multiplexer have been reported both in theory25 and experiment,26 respectively. Here the transporter is known as an optical tweezer. The optical tweezer generation technique is used as a powerful tool for the manipulation of micrometer-sized particles. To date, the usefulness of static tweezers is well recognized. Moreover, the use of dynamic tweezers is now also used in practical work.27–29 Schulz et al30 have shown the possibility of trapped atom transfer between two optical potentials. In principle, an optical tweezer uses the forces exerted by intensity gradients in the strongly focused beams of light to trap and move the microscopic volumes of matter by a combination of forces induced by the interaction between photons, due to the photon scattering effect. In application, the field intensity can be adjusted and tuned to the desired gradient field. The scattering force can then form the suitable trapping force. Hence, the appropriate force can be configured as the transmitter/receiver for performing long distance microscopic transportation.

In this paper, the dynamic optical tweezers/vortices are generated using dark soliton, bright soliton, and Gaussian pulse propagating within an add/drop optical multiplexer incorporating two nanoring resonators (PANDA ring resonator). The dynamical behavior of soliton and Gaussian pulse is well described by Tasakorn et al.31 By using the proposed system, the blood waste and unwanted substances can be trapped and transported (filtered) from the artificial human kidney. Here, the required trapping tool sizes can be generated and formed for the specific blood waste molecules, where finally the clean blood can be obtained and sent to the destination via the through port. However, in practice, several sensors are required for environmental and blood quality control, which will be the topic of future investigation.

Theoretical background

In theory, the trapping forces are exerted by the intensity gradients in the strongly focused beams of light to trap and move the microscopic volumes of matter, in which the optical forces are customarily defined by the relationship below.32

Here, Q is a dimensionless efficiency, n is the refractive index of the suspending medium, c is the speed of light, and P is the incident laser power, measured using the specimen. Q represents the fraction of power utilized to exert force. For plane waves incident on a perfectly absorbing particle, Q is equal to 1. To achieve stable trapping, the radiation pressure must create a stable, three-dimensional equilibrium. Because biological specimens are usually contained in an aqueous medium, the dependence of F on n can rarely be exploited to achieve higher trapping forces. Increasing the laser power is possible, but only over a limited range due to the possibility of optical damage. Q itself is therefore the main determinant of trapping force. It depends upon the NA (numerical aperture), laser wavelength, light polarization state, laser mode structure, relative index of refraction, and the geometry of the particle.

Furthermore, in the Rayleigh regime, trapping forces decompose naturally into two components. Since the electromagnetic field is uniform across the dielectric, particles can be treated as induced point dipoles. The scattering force is given by:32 where

Here, σ is the scattering cross section of a Rayleigh sphere with radius r. 〈S〉 is the time averaged Poynting vector, n is the index of refraction of the particle, m = n/n is the relative index, and k = 2πn is the wavenumber of the light. The scattering force is proportional to the energy flux and points along the direction of the propagation of the incident light. The gradient field (F) is the Lorentz force acting on the dipole induced by the light field, and is given by:32 where is the polarizability of the particle. The gradient force is proportional and parallel to the gradient in energy density (for m > 1). The large gradient force is formed by the large depth of the laser beam. The stable trapping requires that the gradient force is in the – Ž direction, which is against the direction of the incident light (dark soliton valley), and is greater than the scattering force. By increasing the NA, when the focal spot size is decreased, the gradient strength is increased.33 This happens within a tiny system, for instance, in nanoscale devices such as the nanoring resonator.

In our proposal, the trapping force is formed by using a dark soliton, in which the valley of the dark soliton is generated and controlled within the PANDA ring resonator by the control port signals. In operation, the optical tweezers can be trapped, transported, and stored within the PANDA ring resonator and wavelength router, which can be used to form the microscopic volume (molecule) transportation, thus allowing drug delivery via the waveguide.34 The manipulation of trapped microscopic volumes within the optical tweezers has been previously reported.25

Kidney on-chip manipulation

Microfluidics is a burgeoning field with important applications in areas such as medical devices, biotechnology, chemical synthesis, and analytical chemistry.34 The Erickson lab35–40 research interests revolve around the study of micronanofluidics, including advancing flows, delivery, and implantable devices for living organs, in combination with optics.41–43 In this paper, we propose use of the optical trapping tools in the application of blood manipulation dialysis (kidney dialysis) using the PANDA ring resonator systems by incorporating a wavelength router. In the blood cleaner on-chip (Figure 1), we used the same theory of optical trapping and transportation technique for a blood dialysis system, in which the blood flows44,45 into the input port of the PANDA ring resonator, where the PANDA ring resonator system 1 (P1) works the same way as PANDA ring resonator system 2 (P2). The whole blood volume can be trapped and delivered in liquid-core waveguide,46 of both high and low refractive indices, depending on the blood concentration, in which the whole blood concentration is 20% (n = 1.35), 40% (n = 1.35), 60% (n = 1.37).47,48

Figure 1

Schematic diagram of a proposed PANDA ring resonator.

In operation, when blood flows in the waveguide channel,49,50 it is detected by a blood concentrate detector (versatile sensor, 3).51,52 Most important for blood dialysis is protein reabsorption into the renal artery, with the clean blood protein sensor53,54 placed to check the protein quality before release into the urine. The protein sensor will detect the blood protein component and help to regulate blood circulation until it is clean. Additionally, oxygen can be fed into the system via the add port (control) for high quality whole blood which is detected by wireless blood pressure55 before delivery into the renal artery. In this case, the filtrate components are sodium (∼0.4 nm), chlorine (∼0.6 nm), and glucose (∼0.72 nm).56 Our system is integrated to be a single chip, which is equivalent to one Bowman’s capsule consisting of the glomerulus build-up in the capillary vessels.

A schematic of a blood cleaner is as shown in Figure 2, which is formed by PANDA ring resonators and liquid-core waveguide as shown in Figure 3A. The waveguides were constructed by using different sizes and refractive indices as shown in Figure 3B, where in this case the blood cell index is 1.35. The different waveguides with sizes of 5–8 μm and 1 nm were constructed for blood cells and proteins, respectively. The whole blood is input into the system via liquid-core 1 (input port), and the required trapping molecules can be trapped and filtered by liquid-core 2. Finally, the unwanted substances are trapped and filtered via the drop ports. In Figure 2A, the whole blood cells are input into the blood cleaner via the input ports (Ein), which is equivalent to the blood flow into the afferent artery as shown in Figure 2B. After the blood waste substances are filtered by the glomerulus, they are filtrated via the proximal tube. Finally, the clean blood is received via the efferent artery. The blood artery is replaced by the blood waveguide structure, which is formed by the liquid-core waveguide as shown in Figure 3, where the red blood cells (RBCs) with 5–8 μm are input into the system via the input ports (liquid core 1), while the unwanted substances are trapped by the optical tweezers and filtered by the drop ports. Liquid core 2 is used for the trapped proteins, in which the protein molecule size is 1 nm, which is smaller than the RBC, and therefore, the RCBs cannot be transported via the liquid-cores, which means only the unwanted substances are being trapped and transported in the liquid-core 2.

Figure 2

Schematic of an artificial kidney manipulation on-chip system.

Figure 3

Schematic diagram of A) blood waveguide, B) blood waveguide structure.

To form the optical trapping tools, a bright soliton with center wavelength at 1.50 μm, peak power 4 W, pulse 35fs is input into the system via the input port. The coupling coefficients are given as κ0 = 0.5, κ1 = 0.35, κ2 = 0.1, and κ3 = 0.35, respectively. The ring radii are Radd = 100 and 75 μm, RR = 40 and 20 μm, and RL = 40 and 20 μm, respectively. To date, the evidence of a practical device with a radius of 30 nm has been reported by Tasakorn et al.31 Aeff are 300 μm2 (r ≈ 9.77 μm) and 0.5 μm2 (r ≈ 400 nm). In this case, the dynamic tweezers (gradient fields) can be in the form of bright solitons, Gaussian pulses, and dark solitons for trapping the required blood waste. In Figure 4, there are four different center wavelengths of tweezers generated, where the dynamical movements are a) |E1|2, b) |E2|2 c) |E3|2, d) |E4|2, e) through port, and f) drop port signals. In this case, the trapped molecules (blood waste) are filtered and obtained by the drop port. For instance, by using a whole blood index (n) of 1.35, the trapping probe widths of 20 nm at the wavelength center at 1.60 μm are generated (see Figure 4A). More results in terms of coupling constants are shown in Figure 4B, where in this case the tunable trapping can be obtained. In practice, the more reliable device (blood cleaner on-chip) fabrication parameters are the ring resonator radii instead of coupling constants. More results of the optical trapping probes generated within the PANDA ring with different wavelengths are as shown in Figure 5A; the bright soliton is used as the control signal for the tunable result. The output optical tweezers of the through and drop ports with different coupling constants are as shown in Figure 5B, which forms the basis for the selected blood waste molecules. In application, the clean blood can be transported into the human body via the through port. The filtering molecules (urine) are received via the drop port. The advantage of the proposed system is that it can be fabricated on-chip and alternatively operated by a single device.57 The proposed system can be performed as a hemofiltration device, which is 90 μm in depth, 200 μm in width, and 300 μm in length. The unwanted substances can be trapped (filtrated) by the optical gradient field, and can be delivered via the control port (different wavelengths).58 In operation, blood concentration does not affect the optical trapping ability, because the blood refractive index is slightly different, although it may affect the filtration speed.

Figure 4

Results of the trapping tools with different A) sizes and wavelengths, B) tunable tweezers by coupling constant variation, where Rad = 100 μm, RR = RL = 40 μm.

Figure 5

The optical tweezers with different A) sizes and wavelengths, B) tunable tweezers by coupling constant variation, where Radd = 75 μm, RR = RL = 20 μm.

Conclusion

We have shown that blood waste molecules can be trapped and filtered (transported) from the artificial blood cleaner (kidney), which can be performed on-chip. By utilizing the appropriate dark soliton input power, the required trapping tool sizes can be controlled and obtained, where finally the clean blood can be obtained before sending to the final destination (through port). Moreover, oxygen can be fed into the system via the control port, which is available for blood cleaning application. However, in practice, the blood cleaner on-chip system requires a specific environment, in which there are several sensors required to integrate into the system as shown in Figure 1, including bio-sensor, blood sensor, versatile sensor, protein sensor, and blood pressure sensor. Lastly, large molecules may be problematic for the generated trapping tool size. Therefore, the search for new media for guide pipes,59 for instance, nano tube materials, and sensors, will be the next focus of investigation.