Biomedical applications Flashcards
Drug delivery systems
Research on new techniques for drug delivery seeks to develop tools capable of delivering precise quantities of a drug at the right time and as close to the treatment site as possible.
Both implanted and transdermal drug delivery systems have been investigated using microfabrication technologies.
-Transdermal drug release can be an attractive alternative for drugs which cannot be effectively delivered using pills and injections; in fact it overcomes the limitations related to gastrointestinal drug degradation and the inconvenience and pain related to intramuscular and intravenous injections.
An array of micromachined needles for drug delivery was fabricated using the so-called ‘black silicon method’, a reactive ion etching process in which an SF6/O2 plasma etches silicon anisotropically.
Low-frequency ultrasound can make feasible transdermal release of proteins such as insulin across human skin.
Implantable devices
Implantable devices: they are preferred for therapies that require many injections daily or weekly. Implantable drug delivery has other advantages:
-the drug level in the blood could be adapted to variations in physical activity if the drug level is monitored online;
- in some treatments, such as chemiotherapy, the device can be implanted at the place where the drug is needed.
An example of device is a micropump for controlling low flow rates of liquid drugs with high precision and long-term safety. The micrompump is the heart of an impantable drug delivery system fabricated by silicon bulk micromachining and silicon pyrex anodic bonding, and incorporating piezoelectric actuators.
Called the Jewel PUMP, it is a disposable patch that provides sensing blood-sugar levels and then
dispensing insulin as needed. It is made of
2 parts: one re-usable part (electronics, vibration alarm, programming capabilities, remote communication) and one disposable part (reservoir, pumping mechanism and batteries) for an up to 2 weeks’ treatment.
Once both parts are assembled together, the
entirely waterproof unit is attached to the skin with an adhesive patch that contains an auto-inserted infusion cannula with no tubing which can be changed every 3 days.
Smart pill
Among the sensors you can swallow there are miniature gastrointestinal instruments, such as the Smart Pill. It is an insulin-containing capsule about the size of a matchstick that could be implanted in a diabetic patient.
A biosensor protruding from the surface of the pill would detect changes in blood glucose level and send a signal to a small battery pack when the level gets too high. The batteries would respond by
emitting an electrical charge, which causes an artificial “muscle” to contract, opening a pore in the pill and releasing the insulin from a small reservoir.
When the biosensor detects that the patient’s glucose level is back to normal, it stops signaling the battery pack. The batteries stop sending current to the muscle, which relaxes, and the pore closes.
Madou’s group uses polyaniline (PANI), a redox polymer that conducts both ions and electrons, as the framework of their artificial muscle. The polyaniline chains conduct electrons from a metal contact throughout the muscle. Contraction and relaxation are achieved by blending the redox polymer with a hydrogel that expands and contracts in response to electrical stimuli, poly(2-hydroxyethyl methacrylate) (Poly(2-HEMA) in this case.
Probes for neuromuscular stimulation
Functional neuromuscular stimulation: electrical stimulation used to stimulate motor neurons.
It is a single-channel implantable microstimulator that can be inserted into paralyzed muscle groups by expulsion from a hypodermic needle. Power and data to the device are supplied from outside by RF telemetry using an amplitude-modulated 2-MHz RF carrier generated using a high-efficiency class-E transmitter. The transmitted signal carries a 5-bit address which selects one of the 32 possible microstimulators.
The selected device then delivers up to 2 microC of charge stored in a tantalum chip capacitor for up to 200 micros (10 mA) into loads of <800 Ohm through a high-current thin-film iridium-oxide (IrOx) electrode. A bi-CMOS receiver circuitry is used to: generate two regulated voltage supplies (4.5 and 9 V), recover a 2-MHz clock from the carrier, demodulate the address code, and activate the output current delivery circuitry upon the reception of an external
command.
The implant is hermetically packaged using a custom-made glass capsule.
Microsystems for sensory substitution
Developing devices for sensory substitution is tremendously complex because it requires much basic research on many challenging problems such as:
-the design and fabrication of artificial sensors replicating the sensory features of the natural ones as much as possible;
-signal processing and neuro-electronic stimulation techniques to drive nerve fibers and cells that are no longer supplied with inputs from their normal sensors.
-HEARING: A typical cochlear implant stimulates by means of an array of electrodes (typically 20) placed in the scala tympany of the cochlea. An implanted
receiver-stimulator delivers current pulses to selected pairs of electrodes, and receive data specifying the parameters of the stimuli as
well as power from an external speech processor via a transcutaneous inductive coupling.
-SIGHT: providing a functionally useful visual sense to the profoundly blind may be accomplished by video encoding (a miniaturized video camera mounted on a pair of eyeglasses, or even a “silicon
retina” that performs some of the image preprocessing functions of the human retina, and will
make the signals compatible with the neurons they are intended to stimulate). An example of device usable as artificial retinas has been proposed by Sandini et al. The device is a visual sensor
featured by a unique space-variant sensor geometry replicating the distribution of receptors in the human retina: high receptor density in the central area (the fovea), and decreasing receptor density toward the periphery. This structure allows a sort of intrinsic preprocessing and image compression at the sensor level by replicating the same log-polar transformation performed by the human visual system between retinal and cortical images.
Artificial retina
Eyesight can be restored via electrical stimulation with implantable microchips: these devices will be desgigned to electrically stimulate the visual systema t multiple points to create a sense of vision. The perception that results from this stimulation may not be a natural vision, but it may provide enough information for an otherwise blind person to read faces and navigate.
Artificial retina approach: A miniature video camera housed in the patient’s glasses captures a scene. The video is sent to a small patient-worn computer (i.e., the video processing unit – VPU) where it is processed and transformed into instructions that are sent back to the glasses via a cable. These instructions are transmitted wirelessly to an antenna in the implant. The signals are then sent to the electrode array, which emits small pulses of
electricity.
These pulses are intended to bypass the damaged photoreceptors (rods and cones) and stimulate the
retina’s remaining cells, which transmit the visual information along the optic nerve to the brain. This
process is intended to create the perception of patterns of light which patients can learn to interpret as visual patterns.
Electrode arrays consisted of 25 individual 400um diameter platinum disks. Disk electrodes were arranged in a 5x5 square array and supported in a silicone matrix. The electrode spacing was 200 um.
Connection was made to the array via a multi-lead silicone coated cable (diameter < 0.6 mm) composed of 25 individual wires.
The chip has been designed with the biological stimulating constraints determined in clinical studies conducted on patients with RP and AMD. A 600 uA current delivered in 2 ms bipolar pulses is required for retinal stimulation. To prevent flashing, the frequency of stimulation must be at least 60 Hz.
Smart MEMS contact lens
Smart MEMS contact lens with an embedded pressure sensor and antenna that wirelessly
transmits intraocular pressure inside the eye, which can be a symptom of glaucoma. Called the Sensimed Triggerfish®, it is a break-through solution to continuously monitor intraocular pressure. The solution is based on a “smart” contact lens that
uses a tiny embedded strain gauge to monitor the curvature of the eye over a period of, typically, 24 hours, providing valuable disease management data that is not currently obtainable using conventional ophthalmic equipment.
It is a two-part system comprising the smart
contact lens and a small receiver worn around the patient’s neck. In addition to the strain gauge the lens contains an antenna, a tiny dedicated processing circuit and an RF transmitter to communicate the measurements to the receiver.
The lens is powered via the received radio waves and does not need to be connected to a battery. The embedded components are positioned in the lens in such a way that they do not interfere with the patient’s vision.
The lens is fitted by the ophthalmologist and when the patient returns the next day the ophthalmologist removes the lens and receiver.
The implantable telescope
It is a sight-restoring implant.
The implantable telescope is housed in a prosthetic device composed of three primary components: a fused quartz glass capsule that contains wide-angle micro-optical elements, a clear PMMA carrier, and a blue PMMA light restrictor. The sealed optical component is snap-fitted into the carrier plate.
It took the short-road to FDA approval, since it contains no electrical circuitry. The purely mechanical implant houses a 2.5-magnification telephoto lens which is surgically implanted in the eye’s capsular bag after its original lens is removed. It is about the size of a pea (3.6 mm diameter; 4.4 mm length) and is surgically placed inside the eye to render a magnified image on the remaining good retina cells thereby sidestepping the “blind spot” created by macular degeneration.
In Vitro Diagnostics for developing countries
The common denominator of the market of developing countries is the logic of the Point of Care
(POC), namely the implementation of diagnostic activities on site, in contact with the patient, or in
field situations (emergency medicine, battlefield medicine, veterinary medicine, …).
These procedures require the availability of rapid tests, simple to perform, portable and usable
outside the context of an equipped laboratory.
The World Health Organization recently published guidelines for the production of diagnostic devices
intended for developing countries, which can be summarized in the acronym ASSURED:
-Affordable by those at risk of infection
-Sensitive (few false-negatives)
-Specific (few false-positives)
-User-friendly (simple to perform and requiring minimal training)
-Rapid (to enable treatment at first visit) and Robust (does not require refrigerated storage)
-Equipment-free
-Delivered to those who need it
DFA developed a lab-on-a-chip system suitable to be used as a POC device for the analysis of liver functionality in resource-poor settings.
The chip is of the size of a stamp and made of paper, therefore very cheap to produce. The paper is
patterned with wax (using a commercial wax printer) to create hydrophilic reaction chambers and
channels isolated by the surrounding through the hydrophobic wax barrier. A complete test for 3 different liver functions markers is completed in 35
minutes on this chip, starting from a few microliters of blood from a fingerstick. The chip is customizable
to the detection of several other analytes and does not require any additional instrumentation, as the
detection is colorimetric. The system is currently being optimized for clinical use.
Microdevices for genetic diagnostics
