1 History of Bio-microelectromechanical Systems (BioMEMS)
15
For clinical disciplines, including cardiology (Konstantinov et al. 2004),
neurology (Bates 1963), and endoscopic surgery, many appliances were developed by
means of delicate machinery and mechatronic technology long before the BioMEMS
term was conceived. Endoscopic surgery had been performed in the early nineteenth century (Rathet et al. 1974). The development of miniaturization techniques,
in combination with new materials and micro-optic units, led to the earliest use
of BioMEMS technology. A fully implantable pacemaker was developed in 1958
(Konstantinov et al. 2004), and the first hybrid multi-channel cochlear implant was
introduced in 1977 (Hochmair-Desoyer et al. 1983). Table 1.1 summarizes a number
of biomedical devices and their main components along with their fabrications and
main applications (Council 1998; Borenstein 2008; Experts 2019).
The first idea of a BioMEMS biosensor was proposed by Leland Clark and Champ
Lyons, from the Medical College of Alabama, in 1962 (Clark and Lyons 1962).
They proposed a quantification mechanism for glucose which included the action
of an enzyme, a glucose oxidase, that would degrade glucose in the presence of
oxygen and generate gluconic acid. This would create a change in pH that could
be then detected by an electrode. The proposed strategy fully evolved to become a
patent published in 1970 (Wang 2001). In 1976, the first BioMEMS microneedle
for Drug Delivery System (DDS) was reported by Alza Corporation. The reported
device consisted of a DDS for percutaneous administration of a drug comprising
projections, a drug reservoir, and an extend of the projections for penetrating the
stratum corneum (Gerstel and Place 1976).
MEMS technology was not introduced exclusively to the biology and medicine
fields, but also in chemical applications. The first miniaturized ion-sensitive fieldeffect transistor sensor was invented in 1972 by Piet Bergveld. This device was
produced by means of semiconductor and microfabrication techniques (Bergveld
1972). Furthermore, a gas chromatographic air analyzer fabricated on silicon (Si)
wafer was developed by Terry et al. in 1979. The design and the techniques employed
to manufacture this MEMS device were inspired by micromachining fabrication.
This implementation for chemical sensing is another example of MEMS technology
applied to chemical applications (Terry and Jerman 1979). Table 1.1 discusses further
details regarding the fabrication strategy and the applications of both devices.
In 1985, Unipath Inc. (Bedford, United Kingdom) commercialized Clearblue,
a pregnancy test that can be considered the first paper-based microfluidic device.
Clearblue is a diagnostic home kit which relies on specific conjugation of antibodies
to biomarkers for analysis of specific hormones associated with early pregnancy
markers in human urine (Jones and Kraft 2004). Its capacity to give an instantaneous
result is what made it different from previously developed and patented products.
This system was based on the detection of Human Chorionic Gonadotropin (hCG)
applying monoclonal antibodies attached to a Si solid phase, which created a coupled
complex with a specific antigen present during the firsts weeks of pregnancy. When
this complex of antigen–antibody was formed, the labeled immunoglobulins released
a change of color over the solid phase. Therefore, this assay is considered as one
of the first paper-based colorimetric analytic methods in the history of BioMEMS
(Folch 2016).
15
For clinical disciplines, including cardiology (Konstantinov et al. 2004),
neurology (Bates 1963), and endoscopic surgery, many appliances were developed by
means of delicate machinery and mechatronic technology long before the BioMEMS
term was conceived. Endoscopic surgery had been performed in the early nineteenth century (Rathet et al. 1974). The development of miniaturization techniques,
in combination with new materials and micro-optic units, led to the earliest use
of BioMEMS technology. A fully implantable pacemaker was developed in 1958
(Konstantinov et al. 2004), and the first hybrid multi-channel cochlear implant was
introduced in 1977 (Hochmair-Desoyer et al. 1983). Table 1.1 summarizes a number
of biomedical devices and their main components along with their fabrications and
main applications (Council 1998; Borenstein 2008; Experts 2019).
The first idea of a BioMEMS biosensor was proposed by Leland Clark and Champ
Lyons, from the Medical College of Alabama, in 1962 (Clark and Lyons 1962).
They proposed a quantification mechanism for glucose which included the action
of an enzyme, a glucose oxidase, that would degrade glucose in the presence of
oxygen and generate gluconic acid. This would create a change in pH that could
be then detected by an electrode. The proposed strategy fully evolved to become a
patent published in 1970 (Wang 2001). In 1976, the first BioMEMS microneedle
for Drug Delivery System (DDS) was reported by Alza Corporation. The reported
device consisted of a DDS for percutaneous administration of a drug comprising
projections, a drug reservoir, and an extend of the projections for penetrating the
stratum corneum (Gerstel and Place 1976).
MEMS technology was not introduced exclusively to the biology and medicine
fields, but also in chemical applications. The first miniaturized ion-sensitive fieldeffect transistor sensor was invented in 1972 by Piet Bergveld. This device was
produced by means of semiconductor and microfabrication techniques (Bergveld
1972). Furthermore, a gas chromatographic air analyzer fabricated on silicon (Si)
wafer was developed by Terry et al. in 1979. The design and the techniques employed
to manufacture this MEMS device were inspired by micromachining fabrication.
This implementation for chemical sensing is another example of MEMS technology
applied to chemical applications (Terry and Jerman 1979). Table 1.1 discusses further
details regarding the fabrication strategy and the applications of both devices.
In 1985, Unipath Inc. (Bedford, United Kingdom) commercialized Clearblue,
a pregnancy test that can be considered the first paper-based microfluidic device.
Clearblue is a diagnostic home kit which relies on specific conjugation of antibodies
to biomarkers for analysis of specific hormones associated with early pregnancy
markers in human urine (Jones and Kraft 2004). Its capacity to give an instantaneous
result is what made it different from previously developed and patented products.
This system was based on the detection of Human Chorionic Gonadotropin (hCG)
applying monoclonal antibodies attached to a Si solid phase, which created a coupled
complex with a specific antigen present during the firsts weeks of pregnancy. When
this complex of antigen–antibody was formed, the labeled immunoglobulins released
a change of color over the solid phase. Therefore, this assay is considered as one
of the first paper-based colorimetric analytic methods in the history of BioMEMS
(Folch 2016).