Shweta Purushe

Radical Design

Assignment # 2

Potable Microfluidic Blood screening devices

  1. Introduction

Microfluidic devices refer to small devices which process and manipulate fluids in volumes as less as 1 microliter in channels having dimensions between tens to hundreds of micrometers [1, 2].Microfluidic devices allow large, complex and elaborate chemical reactions to occur within a tiny space with superior detection and the added advantage of automation [1]. Due to its channels being so minute it provides superior sensitivity of detection of the sample in questions and fundamentally novel capabilities in controlling the concentration of molecules in space and time. Tests that take a couple of hours in laboratories can be completed in as less as 15 minutes with minimum human errors [1].

Figure 1: Comparison of a microfluidic device with a dime [5]. This device is a chemostat for studying microbial populations. Pnuematic valves are indicated with dyes pumped in to trace the channels.

These devices have myriad applications ranging from chemical analyses, forensics, biological sample analyses and monitoring traces of harmful pollutants in the environment and atmosphere.

However I am interested in the use of these devices for the rapid diagnostics and screening of blood for infectious diseases in developing countries where there is a dearth of medical aid, health care professionals and resources [5].

  1. Motivation

In developing countries, remote conditions, lack of electricity, malnourishment, tropical infectious diseases and lack of immediate and efficient health care provide a scenario for the deployment of rapid diagnostics for communicable and non-communicable diseases. Without adequate medical, equipment, aid and facilities diagnosis becomes cumbersome [4, 5].

Therefore I feel the use of such microfluidic devices can be used for immediate, point-of-center diagnosis of body fluids such as blood, saliva and urine with minimalistic invasive procedures. Use of saliva and urine or other body samples such as sperm, tears, sweat etc is not invasive and does not require absolute sterility. However tests that utilize these samples often are qualitative and do not provide sensitive test results [2]. Therefore use of blood as a test sample seems inevitable.

However in such developing conditions, invasive procedures such as intravenous blood samplingleads to other further complications such as transmission of infections due to contaminated needles or sepsis due to lack of sterility. Therefore microfluidic devices that utilize as less as a single microliter (µl) of blood using a simple finger prick seems to be a solution for the abovementioned problems in the near future [5].

In addition, a further advantage of such devices is that, whole blood, serum and plasma all can be sampled with equal efficiency. The few microliters of blood collected from the patient can be tested for more than one infection, for example the same device can be used to test for presence of HIV and syphilis in the blood simultaneously.

I believe that these devices bear the potential of using only a few microliters of blood and providing all possible information about the patient, right from immunization records to recent infections, from medications consumed to as far as presence of cancerous genes.

  1. Evolution

The miniaturizing of lab tools onto a small device started as early as the 1950s while integrating semiconductors on microelectronic chips. These were initially used as sensor devices such as pressure sensors and only later towards the late 1960s were fluid handling devices developed. They were used as dosing devices, pumps, pressure control valves. Initially being used in chemical analysis the first microfluidic device was developed at Stanford for gas chromatography, a process of separating a mixture of gases into its pure individual components. This was followed by its use by IBM for ink-jet printers [5].

However the sudden interest in microfluidic devices started in 1990s when µTAS started providing genomic analysis tolls on a small chip. There was also interest from DARPA (Defense-Advanced Research Projects Agency) for the ability of such devices to analyze the blood specimens of soldiers for detection of chemical/biowarfare agents [5]. Ever since researchers are trying to add as many laboratory procedures and tools to these devices such that steps such as sample collection, sample pretreatment, sample testing, test results and analysis all are available on a single microfluidic device. The search of cost effective biocompatible materials for manufacturing is also another focus of research.

  1. Design and Applications

Being interested in application of microfluidic devices for detection of infectious diseases I will explain the design and functioning of these devices from the detection point of view.

Figure 2: Flow chart of functioning of the fluid device. The arrows indicate passive delivery of multiple reagents which requires no moving parts on the chip [1].

Figure 3: The ELISA (Enzyme-linked immune-sorbent assay) principle is used for detecting the presence of HIV and Syphilis proteins in the patient’s blood sample [1].

  • The test detects presence of anti-HIV and anti-syphilis antibodies present in the patient’s blood. These bind to the antigens (proteins of HIV and syphilis) fixed onto the chip.
  • Gold labeled goat antibody and silver reagents help increase the sensitivity and amplify detection of results.
  • If the patient posses HIV and/or syphilis, he will posses anti-HIV and anti-syphilis antibodies in his blood which will bind in step2 and give positive results as seen in step4.
  • The signals that are emitted can be detected and read using low cost optics, using cell phones or can even be examined using the naked eye!
  • The device can then be inserted into palm-sized detectors which then can give quantitative results. Research also shows that these detectors can be clubbed with satellite communication networks which can immediate send information about the test, geo and time stamped via email. However this is possible only in developed countries with ell phone and satellite networks.

Figure 4: The Microfluidic device (left). Each device can be used to accommodate seven samples with holes for coupling of reagent and chemical loaded tubes. (Left) The flow of blood through channels that are a few µm (micrometers) thick [1].

  • The sample is loaded at one end and the fluids are made to travel through the device using the vacuum created by a syringe connected to the exit (Figure 4). The fluids traverse the minute channels through the reagents and are finally collected by the syringe.
  1. Why is this radical?
  • This device can yield results using less than 1 µl of sample which alleviates the need of collecting an entire test tube of blood using needles. This makes the process non invasive, prevents infections transmitted through contaminated needles and prevents sepsis due to lack of sterility [1].
  • The device had sensitivity and specificity is very high. (98% and 100% respectively for HIV and 82-100% and 97% respectively for syphilis)[1].
  • The device can be used as an early, easy, rapid and efficient diagnostic for several infectious blood borne-infections simultaneously and serve in containment of infectious diseases, serve as indicators for epidemiological studies (detecting positively infected individuals in remote and developing countries is difficult)[1, 2].
  • The cost of manufacture is as less as $0.10 and can easily be produced at a high throughput (1 chip every 40seconds) [1].
  • The process if automated, requires no moving parts, requires no electricity or external instrumentation, the reagents remain stable in hostile conditions and with slight training can be used as a personal testing system. No health care professional will be required for monitoring, because the signals can be detected easily using the naked eye.
  • The test time is as less as 15 minutes, and the silver reduction yields sufficient result within 5 minutes, with only minimal background development [1].
  1. Conclusion

With the above mentioned powerful and advanced detection systems such microfluidic cassettes could be provided in the remotest of territories in developing countries. Even in developed countries, detection of certain infections could be done by patients at home with minimum training.

With improved automation, provisions for reuse, better environmental compatibility and with the power of detecting everything possible about the patient’s health, this little device could serve as a DNA print opening doors for personalized medicine, in vivo implants and efficient health management standards.

  1. References

1.Curtis.C et al “Microfluidics-based diagnostics of infectious diseases in the developing world” Nature Medicine17,1015–1019(2011).

2.Rosamund Daw& Joshua Finkelstein et al “Introduction Lab on a chip” Nature 442, 367 (27 July 2006)

3.Curtis D. Chin,Vincent Linder and Samuel K. Sia et al “Lab-on-a-chip devices for global health: Past studies and future opportunities” Lab on a Chip 7,41-57 (2007)

4.Jurgen Mairhofer , Kriemhilt Roppert and Peter Ertl et al “Microfluidic Systems for Pathogen Sensing: A Review” Sensors 9, 4804-4823 (2009)

5.George M. Whitesides et al “The origins and the future of microfluidics”Nature 442, 368-373 (27 July 2006)